Many research labs are busy working away at developing better tissue engineering techniques to grow replacement parts for aged and damaged human bodies. Here's a lab at Case Western that has developed a new and promising cartilage growth technique.
A lab discovery is a step toward implantable replacement cartilage, holding promise for knees, shoulders, ears and noses damaged by osteoarthritis, sports injuries and accidents.
Self-assembling sheets of mesenchymal stem cells permeated with tiny beads filled with growth factor formed thicker, stiffer cartilage than previous tissue engineering methods, researchers at Case Western Reserve University have found. A description of the research is published in the Journal of Controlled Release.
"We think that the capacity to drive cartilage formation using the patient's own stem cells and the potential to use this approach without lengthy culture time prior to implantation makes this technology attractive," said Eben Alsberg, associate professor in the departments of Biomedical Engineering and Orthopaedic Surgery, and senior author of the paper.
Think of all the people with painful knees, fingers, and other joints because their cartilage has worn down. The ability to fix all these damaged joints would cut pain and increase mobility. Increased mobility would also increase exercise and muscle mass.
Among successful tissue engineering projects so far: functional replacement mouse pituitary glands, replacement urethras for kids, and bladders for adults. The list is going to grow every year and the rate of growth is going to accelerate.
As we age lots of our parts wear out and malfunction. What we need: replacement parts. So every time yet another research group reports success growing replacement organs it is time for cheer. Some lucky Japanese mice have already benefited. Keep an eye out for mice trying to sneak on Japan-bound airplanes.
Last spring, a research team at Japan's RIKEN Center for Developmental Biology created retina-like structures from cultured mouse embryonic stem cells. This week, the same group reports that it's achieved an even more complicated feat—synthesizing a stem-cell-derived pituitary gland.
Click thru to read the details.
Tissue engineering to create the most complex glands and organs requires presenting a dynamically changing 3-dimensional environment to the cells that make up the organ being grown. The cells need to get shifting gradients of chemical signals that attempt to replicate the chemical environment of a developing fetus. A very difficult challenge both because the changing local fetal chemical environment has to be identified and also then replicated.
Growth of organ replacements is one of the most radical forms of rejuvenation. Rather than try to send in repair cells or gene therapies to do, at best, partial fixes the complete replacement of an organ effectively turns the biological clock on it back to complete youthfulness. I expect some reading this will live to see the day when whole organ replacement with vat-grown organs becomes routine - at least for those who can afford the treatment.
Tissue engineering to fix hearts with muscle cell patches (which is already going into clinical trials) might be improved with gold nanowires to better coordinate the muscle cells that come in a patch.
A team of physicians, engineers and materials scientists at Children's Hospital Boston and the Massachusetts Institute of Technology have used nanotechnology and tiny gold wires to engineer cardiac patches, with cells all beating in time, that could someday help heart attack patients.
As reported online by Nature Nanotechnology on September 25, the addition of gold wires to the engineered heart tissue make it electrically conductive, potentially improving on existing cardiac patches. Such patches are starting to go into clinical trials for heart patients.
"If you don't have the gold nanowires, and you stimulate the cardiac patch with an electrode, the cells will beat only right where you're stimulating," says senior investigator Daniel Kohane, MD, PhD, of the Laboratory for Biomaterials and Drug Delivery at Children's Hospital Boston. "With the nanowires, you see a lot of cells contracting together, even when the stimulation is far away. That shows the tissue is conducting."
Tissue engineering is on the verge of becoming a huge field. The revenues from early entrant products will fund growth in development for new types of patches and eventually whole organs. 20 years from now the idea of having to live with a tennis elbow or a bad anterior cruciate ligament or a damaged part of your heart will seem so historical.
Patches of muscle cells grown with nanowires will probably be better organized as a result.
After incubation, the patches studded with the gold nanowires were thicker and their heart muscle cells better organized.
These scientists are now going to move on to implanting patches in animal models. Then come humans.
In the longer term gold nanowires might only get used when growing the tissue patches. For implantation the nanowires might be a transitional technology until it becomes possible to guide nerve cells into growing new connections to hook directly into implanted heart patch tissue.
WINSTON-SALEM, NC – March 7, 2011 – Researchers at the Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center and colleagues reported today on a new advance in tissue engineering. The team is the first in the world to use patients’ own cells to build tailor-made urinary tubes and successfully replace damaged tissue.
In an article published Online First by The Lancet, the research team reports replacing damaged segments of urinary tubes (urethras) in five boys. Tests to measure urine flow and tube diameter showed that the engineered tissue remained functional throughout the six-year (median) follow-up period.
“These findings suggest that engineered urethras can be used successfully in patients and may be an alternative to the current treatment, which has a high failure rate,” said Anthony Atala, M.D., senior author, director of the Wake Forest Institute for Regenerative Medicine and a pediatric urologic surgeon. “This is an example of how the strategies of tissue engineering can be applied to multiple tissues and organs.”
Humans differ from cars in that cars can have their parts replaced when the parts wear out. When crucial human parts wear out we get sick and eventually die. When scientists succeed to growing replacement parts for all of our bodies (except our brains) then death due to aging will become avoidable as long as brain rejuvenation techniques can be made to work.
Atala's team has previously succeeded in growing replacement bladders that work in humans. Atala's team is also working on development of tissue engineering techniques to repair the bodies of damaged soldiers. More successes from his team and other labs will keep getting reported. Many body parts will be replaceable in 10 years.
Maria Konovalenko points to an impressive feat of tissue engineering. Using the cartilage of a donor trachea to form a scaffolding the stem cells from the nose and bone marrow of a 19 year old girl were grown on the cartilage scaffolding and then the new windpipe was implanted as a replacement for a cancerous trachea.
A British teenager has been given a new windpipe grown from her own stem cells in a pioneering operation. The 19-year-old has now been discharged after having the procedure in Italy.
Curiously, this is not the first success at growing replacement tracheas. Whether the stem cells are first grown on the trachea for a while before implantation has differed in the few times trachea replacements have been installed. Click thru to read the details.
The use of donor organ non-cell scaffolding to grow replacement organs has also been done with rat livers. MIT researchers have created scaffolding for growing knee and other joint tissue. Other research shows promise for creating scaffolding to grow heart tissue replacements.
These days people usually don't die from a heart attack. But the damage to heart muscle is irreversible, and most patients eventually succumb to congestive heart failure, the most common cause of death in developed countries.
Stem cells now offer hope for achieving what the body can't do: mending broken hearts. Engineers and physicians at the University of Washington have built a scaffold that supports the growth and integration of stem cell-derived cardiac muscle cells. A description of the scaffold, which supports the growth of cardiac cells in the lab and encourages blood vessel growth in living animals, is published this week in the Proceedings of the National Academy of Sciences.
Tissue engineering is all about creating scaffolding that provides a structure for cells to organize to create new tissues.
Ratner and his colleagues built a tiny tubular porous scaffold that supports and stabilizes the fragile cardiac cells and can be injected into a damaged heart, where it will foster cell growth and eventually dissolve away. The new scaffold not only supports cardiac muscle growth, but potentially accelerates the body's ability to supply oxygen and nutrients to the transplanted tissue. Eventually, the idea is that doctors would seed the scaffold with stem cells from either the patient or a donor, then implant it when the patient is treated for a heart attack, before scar tissue has formed.
The scaffold material was tested in a living rat's heart.
Researchers also implanted a bare scaffold into a living rat's heart to verify the scaffold's biocompatibility. Results showed that after four weeks the heart had accepted the foreign body, and new blood vessels had penetrated into the scaffold.
Embryonic stem cell research gets a lot of press attention. But tissue engineering as a field seems more challenged by how to create 3-D scaffolding structures that will guide cells to form tissue to repair 3-D structures in existing organs.
Why can cars be kept operational decades longer than they were originally designed to last? Because repair shops can replace worn out and broken parts. We humans can't replace our worn out parts because we have no way to make replacements for most of our parts. With that thought in mind check out how researchers at Massachusetts General Hospital have grown replacement livers by using the vasculature and other structure of a freshly dead liver to grow a new liver.
Scientists at Massachusetts General Hospital in Boston have taken the first steps toward building functional, transplantable livers. In a study in rats, published online today by Nature Medicine, the researchers took donor livers, gently stripped them of their cells while leaving other material intact, and then used the remaining structure as a scaffold on which to grow healthy liver cells. The result was a nearly complete organ that was transplanted into the rats and remained functional for up to eight hours.
The strip away the liver cells to retain the scaffolding, add new liver cells and, and then grow a new liver in a nutrient bath.
One obvious problem with this approach is that it requires an existing organ to use as a starting point. Given that someone with a failing organ still typically needs the remaining functionality of their organ they can't use their own organ's blood vessels as a scaffolding to grow a replacement organ in a culture. The development of better artificial organs could enable the removal of more types of diseased organs without immediate death. Then a patient could be kept alive (albeit connected to machines) while a new replacement part is grown.
Of course, lots of people die every day who leave behind livers. If their liver cells could be removed and a person with a sick liver could donate their own cells to grow a new liver then the immune rejection problem would be much smaller even though the scaffolding used to grow the liver would be from a different person than the one who gets the new liver.
Click thru and read all the details. This approach still has some unsolved problems. But the scientists working on it are optimistic they can solve all these problems within 10 years. Then humans will become more like cars: able to be kept on the road with replacement parts.
UC Irvine scientists have created an eight-layer, early stage retina from human embryonic stem cells, the first three-dimensional tissue structure to be made from stem cells.
It also marks the first step toward the development of transplant-ready retinas to treat eye disorders such as retinitis pigmentosa and macular degeneration that affect millions.
"We made a complex structure consisting of many cell types," said study leader Hans Keirstead of the Reeve-Irvine Research Center and the Sue and Bill Gross Stem Cell Research Center at UCI. "This is a major advance in our quest to treat retinal disease."
One of the things I wonder about future rejuvenation therapies is how much of the repair and replacement will be done by swapping out bigger parts like, say, a retina or a whole organ. Will stem cells and gene therapy be able to repair most existing parts in place? Or will we need to have replacements for most of our organs grown in vats and then swapped into our bodies with surgery? I'd prefer repair in place in order to avoid large numbers of risky surgeries. But replacement of whole organs will be called for due to either urgency of the need or because it will be hard to get stem cells to correctly fill in gaps in structure that are too large and complex for cell therapies to target.
The reason cars can keep running indefinitely is because their worn out parts can be replaced. By contrast, we have very limited abilities to replace worn out human parts. The development of tissue engineering techniques for growing an implanting replacement parts holds the promise of making humans as repairable as cars. Some University of Washington researchers have developed human heart muscle patches that include blood vessels that allow larger patches to be grown.
University of Washington (UW) researchers have succeeded in engineering human tissue patches free of some problems that have stymied stem-cell repair for damaged hearts.
The disk-shaped patches can be fabricated in sizes ranging from less than a millimeter to a half-inch in diameter. Until now, engineering tissue for heart repair has been hampered by cells dying at the transplant core, because nutrients and oxygen reached the edges of the patch but not the center. To make matters worse, the scaffolding materials to position the cells often proved to be harmful.
The researchers were able to grow blood vessels along with the muscle. Then when they transplanted the tissue patches into rats the blood vessels in the patches formed connections with the blood vessels in the rats.
Stevens and her fellow researchers added two other types of cells to the heart muscle cell mixture. These were cells similar to those that line the inside of blood vessels and cells that provide the vessel's muscular support. All of the heart muscle cells were derived from embryonic stem cells, while the vascular cells were derived from embryonic stem cells or a variety of more mature sources such as the umbilical cord. The resulting cell mixture began forming a tissue containing tiny blood vessels.
Better techniques for tissue engineering are key to the development of human replacement parts. Replacement parts are key to human rejuvenation and the reversal of the aging process. Tissue engineering is more than just stem cell research (as important as that is). Tissue engineering involves the development of the ability to grow organized complex 3 dimensional groupings of cells that form a part equivalent to some existing part in our bodies.
Traditional gum grafting surgery requires surgically excising tissue from the roof of the mouth (the palate) to replace the gum tissue lost around the teeth. Unfortunately, removing tissue from the roof of the mouth extends recovery time and is a major source of patients’ discomfort or pain. According to the American Academy of Periodontology, periodontal disease is the primary cause of tooth loss in adults aged 35 and older. Periodontal disease includes gum recession, also called gingival recession, which can result in tooth root decay and tooth loss.The new tissue regeneration application from Tufts uses platelet concentrate gel applied to a collagen membrane as the graft instead of using tissue from the roof of the mouth. The graft is soaked in the patient’s platelets, using blood drawn in the same visit. Placed over the receding tooth root, the graft is then surgically secured.In order to examine three-year efficacy of the treatment, measurements were taken from six patients in the gum recession area at baseline, 6, and 36 months after surgery. At six months, 24 out of 37 teeth from the six patients had complete root coverage (65 percent). At 36 months, 21 out of 37 teeth from the six patients had complete root coverage (57 percent). The authors said that the recession over three years was minimal and that the results are comparable to traditional gum grafting surgery.
We need methods for engineering tissue to get it to grow where we want and to become the types of tissue we need for repair. Success stories like the one above demonstrate that guided tissue growth isn't only in our distant science fiction future. It is in our short term future as well.
We need ways to grow replacements for worn out body parts. Then we can become as repairable as cars. While embryonic and pluripotent stem cells get the lion's share of press attention the scientists who labor away at solving tissue engineering problems are making contributions every bit as important. I expect tissue engineering problems to be the long pole in the tent for developing replacement body parts. With this thought in mind, some researchers at MIT have developed implantable materials that stimulate mesenchymal stem cells to produce bone and cartilage. Their technique works in goats.
CAMBRIDGE, Mass.--MIT engineers and colleagues have built a new tissue scaffold that can stimulate bone and cartilage growth when transplanted into the knees and other joints.
The scaffold could offer a potential new treatment for sports injuries and other cartilage damage, such as arthritis, says Lorna Gibson, the Matoula S. Salapatas Professor of Materials Science and Engineering and co-leader of the research team with Professor William Bonfield of Cambridge University.
"If someone had a damaged region in the cartilage, you could remove the cartilage and the bone below it and put our scaffold in the hole," said Gibson. The researchers describe their scaffold in a recent series of articles in the Journal of Biomedical Materials Research.
The technology has been licensed to Orthomimetics, a British company launched by one of Gibson's collaborators, Andrew Lynn of Cambridge University. The company recently started clinical trials in Europe.
The scaffold has two layers, one that mimics bone and one that mimics cartilage. When implanted into a joint, the scaffold can stimulate mesenchymal stem cells in the bone marrow to produce new bone and cartilage. The technology is currently limited to small defects, using scaffolds roughly 8 mm in diameter.
You can bet that goats who suffer joint injuries while scampering along steep hillsides and down rocky landscapes will be happy to hear that scientists have finally listened to their complaints.
BERKELEY, CA – Scientists at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory can now control how cells connect with one another in vitro and assemble themselves into three-dimensional, multicellular microtissues. The researchers demonstrated their method by constructing a tailor-made artificial cell-signaling system, analogous to natural cell systems that communicate via growth factors.
Their method of attaching the DNA uses artificial sugars. They are working on other ways to attach the DNA.
The researchers enabled cells to react with other cells in a controlled way by coating the cell surfaces with DNA (not where DNA is normally found!). First they induced the cells to express artificial sugars bearing special chemical groups. Lengths of synthetic DNA, introduced into the cell-growth medium, were equipped to recognize these synthetic sugars on the cell surfaces and chemically bind to them.
They were able to combine two cell types where one cell type needed the other cell type.
Bertozzi and Gartner applied these methods to build a signaling network where one kind of cell controls the growth of a second kind of cell. They maintained the survival and replication of hematopoietic progenitor cells (a kind of stem cell for blood cells), which depend on the presence of the growth factor interleukin-3, by combining them in microtissues with CHO cells (Chinese hamster ovary cells) that were engineered to secrete interleukin-3.
When the two cell types were randomly mixed, the stem cells didn’t grow. But structured microtissues built from the two cell types stimulated their own growth, forming a simple artificial signaling network that behaved much like the natural networks that control immune-cell expansion or tumor proliferation.
Tissue engineering to create organs outside of the body is a difficult problem. We need ways to grow or build replacement organs. One way is to genetically engineer pigs to grow human-compatible organs. Another way might be to create a really complex chemical environment that'll act like an artificial womb that only grows part of the body. But some researchers such as the Lawrence Berkeley folks are just trying to build up organs with methods for laying down cells in 3 dimensions. My guess is all these approaches have a future with each suited better to particular organs.
Why make complex chemical plants to produce pharmaceuticals when you can genetically engineer some animals to do it in their own internal chemical factories? The US Food and Drug Administration will soon approve the first genetically engineered animals created for commercial use. For some applications the milk must be processed to extract the drug. But you can easily imagine cows and goats who produce a milk that you drink to get the drug.
In a surprise move, it seems likely the first genetically engineered animal approved for commercial use won't be a fast-growing salmon, as was expected, but a goat that produces an anti-clotting drug in its milk.
We've already got genetically engineered plants working for us. We'll have many genetically engineered animals working as chemical factories in the future. We'll also eventually have genetically engineered service animals to help us in daily tasks. Genetic engineering will speed up the breeding of animals that humans have been doing for thousands of years.
Rather than continue to have large numbers of people donate blood to isolate needed platelets a group at Ohio State University is producing platelets using stem cells in laboratory bioreactors.
COLUMBUS, Ohio – It might be possible to grow human blood platelets in the laboratory for transfusion, according to a new study at The Ohio State University Medical Center.
The findings, published in the January 1, 2009 issue of the journal Experimental Hematology, might one day enable blood banks to grow platelets continuously and in quantities that can ease the chronically tight supply of these critical blood components.
About 13 million platelet concentrates are collected annually in the United States at a cost of about $1 billion. They are needed by people who lack platelets or whose platelets function improperly, such as certain cancer chemotherapy patients, bone marrow transplant patients, trauma patients given massive blood transfusions and people with aplastic anemia.
Reports about stem cells getting manipulated to produce useful products are great news. An industry built up around getting people to donate blood won't produce all that much in the way of biotechnological innovations since the most important part of the process happens in a person's body before they donate the blood. A movement of that process into bioreactors creates an industry that will improve the state of the art in tissue engineering. The more types of tissues that get grown in bioreactors the sooner we'll get to full internal organs getting grown outside the body to serve as needed replacement parts as we age.
Stem cells isolated from umbilical cord blood were combined with growth factors to stimulate production of megakarocyte cells which shed platelets. This is all good.
For this study, Lasky and his colleagues isolated hematopoietic stem cells, which produce blood cells, from blood taken from umbilical cords following normal, full-term deliveries. The stem cells were grown to greater numbers, then added to the bioreactors – chambers with several layers for gas and growth-media control. Control cells were grown in culture flasks. Other attempts to grow platelets have usually used culture flasks or similar two-dimensional systems.
After a few days of growth, a solution of growth factors was added to both groups to stimulate the cells to form large, bone-marrow cells called megakaryocytes, which shed bits of themselves as platelets.
The three-dimensional bioreactor produced up to 1.2 million platelets per day, with production continuing for more than 32 days, while the two-dimensional system generated a maximum of about 350,000 platelets per day over a ten-day period.
This research team is working on ways to increase yields. They are at an early enough stage that many process improvements lie ahead.
A new biomaterial developed by Cartilix, a biotech startup based in Foster City, CA, could dramatically improve the success rate of knee-cartilage repair surgery, making the procedure more accessible to patients with bad knees. The new material, called ChonDux, consists of a polymer hydrogel that, when injected into the knee during surgery, guides the regeneration of cartilage by stimulating repair cells in the body.
So far the technique has been tested on animals and on a small human group in Europe. So you can't get this treatment unless you can get yourself enrolled in a coming US clinical trial.
This hydrogel enhances an existing knee surgery repair technique called microfracture. The microfracture approach involves drilling lots of small holes in bone where the cartilage is missing. A blood clot formed in that area signals stem cells to rush in and do repair. This new enhancement of that approach reduces the amount of scar tissue that forms and increases cartilage formation.
ChonDux consists of a hydrogel made of polyethylene glycol--a polymer commonly used in a variety of medical products--and a bioadhesive to keep the hydrogel in place after injection. First, the surgeon coats the inside of the cavity where the cartilage is missing with the bioadhesive and then, as in microfracture, drills tiny holes into the bone next to the cavity. Then the surgeon fills the empty space with the hydrogel and shines UVA light on the material, which causes the polymer to harden from a viscous liquid into a gel.The blood clot that forms from the microfracture then gets trapped in the hydrogel.
The bioadhesive in this case is chondroitin sulfate which many people take as a supplement to reduce joint pain.
One of the biggest problems with transplanting biomaterials is getting the mostly aqueous material to stick in a very slippery space, says Jennifer Elisseeff, a biomedical engineer at Johns Hopkins University, who developed ChonDux and cofounded Cartilix. The adhesive in this case consists of chondroitin sulfate--a natural component of cartilage that is chemically modified to bind to the healthy cartilage surrounding the defect, as well as to the hydrogel. "It acts like a primer that helps paint stick to the wall," Elisseeff said at a panel at the recent EmTech conference in Cambridge, MA. The adhesive prevents scar formation between the new and old cartilage.
This approach is fairly low tech. The researchers didn't grow up stem cells for injection into the knee. They also didn't use gene therapy to instruct cells to do repair. Yet those higher tech methods are needed. The existing microfracture technique has a much lower success rate in older people - probably because their stem cells are less vigorous. Younger stem cells or stem cells primed up to do repair could boost success rates.
The drilling of holes in bone as a way to stimulate repair seems crude. We need ways to coat a surface with repair stimulating materials without causing damage. Simulate the damage biochemically rather than cause real damage. Those techniques will come as the compounds that stimulate repair become better understood and more manipulable.
Scientists in a laboratory at Georgia Tech have developed a way to grow tendons that merge into bone. Previous lab-grown tendons lacked the ability to attach to bone.
Tissue engineering can produce tendons, cartilage, and even bladders. But only now have researchers managed to make different tissues blend into one another, as they do naturally in the body.
Such gradients are necessary for some structures and organs to function properly, says bioengineer Andrés García, who with colleagues at the Georgia Institute of Technology demonstrated a way to grow tendons that gradually "fade" to bone at one end.
We need the ability to grow replacement parts as our parts wear out from age. Given the ability to grow replacement parts we can replace old parts of our body with more youthful parts and make ourselves young again.
An engineered material that can be injected into damaged spinal cords could help prevent scars and encourage damaged nerve fibers to grow. The liquid material, developed by Northwestern University materials science professor Samuel Stupp, contains molecules that self-assemble into nanofibers, which act as a scaffold on which nerve fibers grow.
Stupp and his colleagues described in a recent paper in the Journal of Neuroscience that treatment with the material restores function to the hind legs of paralyzed mice. Previously, researchers have restored function in the paralyzed hind legs of mice, but those experiments involved surgically implanting various types of material, while the new substance can simply be injected into the animals. The nanofibers break down into nutrients in three to eight weeks, says Stupp.
I hope researchers are able to pretty quickly try this treatment in other animals and that human trials aren't too far off.
Most of us are going to live to see the day when people with severed spinal cords regain the ability to feel and walk again.
Researchers at Johns Hopkins have discovered that blood vessels in the head can guide growing facial nerve cells with blood pressure controlling proteins. The findings, which suggest that blood vessels throughout the body might have the same power of persuasion over many nerves, are published this week in Nature.
“We’re excited to have stumbled across another family of proteins that can tell a growing nerve which way to grow,” says David Ginty, Ph.D., a professor of neuroscience at Hopkins and investigator of the Howard Hughes Medical Institute. “But the really interesting thing is that the nerves appear to use blood vessels as guideposts to direct their growth in one of several possible directions.”
The research team studied in mice a group of about 15,000 nerve cells known as the superior cervical ganglia, or SCG, which extend projections that innervate various structures in the head including the eyes, mouth and salivary glands. The SCG sits in a Y-like branching point of the blood vessel in the neck that supplies the head with blood, the carotid artery. In the developing embryo, nerve projections grow out of the SCG and grow along one of the two branches of the carotid artery; the nerves that grow along the internal carotid innervate the eyes and mouth among other head structures, and those that grow along the external carotid innervate the salivary glands.
These researchers are trying to figure out why the nerves follow the blood vessels. That knowledge will be useful in figuring out how to guide nerve growth for therapeutic reasons.
Cells taken from a person can be grown into blood vessels and reimplanted into the same person. This avoids immune rejection problems.
From a snippet of a patient’s skin, researchers have grown blood vessels in a laboratory and then implanted them to restore blood flow around the patient’s damaged arteries and veins.
It is the first time blood vessels created entirely from a patient’s own tissues have been used for this purpose, the researchers report in the current issue of The New England Journal of Medicine.Cytograft Tissue Engineering of Novato, Calif., made the vessels, in a process that takes six to nine months.
The repair and replacement of worn out and broken parts is the future of medicine. The accumulation of techniques for replacing old parts will eventually lead to the halting and reversal of the aging process. This report is one step down the road toward full body rejuvenation.
If you read the full article above you'll learn that the first experimental subjects for a Novato California company were in Argentina - not exactly close by. I suspect this says something about medical regulation in America today. The Argentines were on hemodialysis for kidney failure and had what the report below characterized as "typical risk factors for end-stage renal disease". You might expect regulatory agencies to grant greater freedom of action to try out new treatments on people who are looking death in face. But this company used subjects from another country. I fear excessive regulatory obstacles in the way of new treatment development are costing lots of lives.
See the correspondence the experimenters sent to The New England Journal of Medicine entitled Tissue-Engineered Blood Vessel for Adult Arterial Revascularization.
British scientist Simon Hoeurstrup and heart surgeon Magdi Yacoub claim that in 3 to 5 years they will be able to grow replacement heart valves from a patient's own bone marrow stem cells.
In the tissue engineering approach favored by Yacoub and Hoerstrup, the patient's own stem cells -- taken from bone marrow -- are isolated and expanded in the laboratory using standard cell culture techniques.
They are then "seeded" onto a special matrix in the shape of a heart valve that is positioned in a device called a "bioreactor" that tricks the cells into growing in the right shape.
They've already tested this technique with sheep cells.
One problem with extracting bone marrow stem cells comes with age. Potential leukemia replacement cell donors are screened for age. People in their 60s aren't considered good bone marrow cell donors. Well, stem cells extracted from older people to grow heart valves might grow poorly. But given that the extracted cells won't be reimplanted the development of techniques to stimulate those cells (e.g. lengthen their telomeres) more rapidly would pose few risks.
As biogerontologist Aubrey de Grey points out once we can grow replacement parts we can keep our bodies youthful for many centuries.
As long time readers know, a recurring theme on FuturePundit is that the use of computer industry technologies to perform biological manipulations will make biotechnology increasingly advance at the rate of computer technology. We all know that's a really fast rate of advancement. Thomas Boland has further refined and improved his technique for laying down cells using a commercial inkjet printer.
Research from Clemson University shows that producing cardiac tissue with off-the-shelf inkjet technology can be improved significantly with precise cell placement. Tom Boland, associate professor in Clemson’s bioengineering department, along with Catalin Baicu of the Medical University of South Carolina, present their findings today (2-18) at the American Association for the Advancement of Science (AAAS) Conference in San Francisco.
Since Boland’s discovery in 2004, “printing” tissue using 3-D printers has focused on printing materials for hard tissue applications, such as in the jawbone. The study presented at AAAS focused on precise placement of cells, which is essential to achieving function in soft tissue, such as the heart. In this study, live, beating heart cells were achieved more efficiently.
How about printing out a new organ?
The latest advance: lay down the scaffolding and cells at the same time using different nozzles. Color printers have 3 nozzles for 3 colors and so this advance builds upon that capability.
“The breakthrough with this technology is that cells now can be precision-placed virtually instantaneously with the materials that make up a scaffold to hold the cells in place,” Boland said. Precision placement of the cells is achieved by filling an empty inkjet cartridge with a hydrogel solution (a material that has properties similar to tissue) and another inkjet cartridge with cells. The printing is accomplished much in the way that color photographs are made, activating alternatively the hydrogel and cell nozzles.
Computer technology is mass-produced and cheap. Some day biotechnology will be cheap as well. Production of internal organs and other body parts will become very cheap. Microfluidic chips and robotic devices will build replacement parts and gene therapies.
Also see my previous post Modified Printers Used For Tissue Engineering. Also, inkjet printers are not the only commonplace cheap computer accessory getting used in novel ways to work with biological materials. CD players have uses in biology as well. See my posts CD Player Turned Into Bioassay Molecule Detection Instrument and CD Will Simultaneously Test Concentrations Of Thousands Of Proteins.
The process used to make the scaffold is based on a technique called electrospinning, which produces polymer fibres down to nano-scale by applying an electric field. However, the team has developed a new method of making aligned-fibre 'mats' from the same biodegradable polymers. These promote the growth of nerves, tendons and cartilage.
Prof Tony Ryan, who leads the research at Sheffield University, said: 'Normal electrospinning leaves the fibres running in random directions. We have developed a method to control the orientation of the fibres by controlling the electric field. This is now being patented.'
Ryan said the breakthrough was as much about understanding cell behaviour as the scaffold. 'What we have shown is that cells know the order in which they need to build, so you get the same strata in the new skin as you had in your own. '
The researchers see human trials as still at least 2 years off.
Knee cartilage injuries can be effectively repaired by tissue engineering and osteoarthritis does not stop the regeneration process concludes research led by scientists at the University of Bristol.
The study, "Maturation of tissue engineered cartilage implanted in injured and osteoarthritic human knees", published in the July 2006 (Volume 12, Number 7) issue of Tissue Engineering, demonstrates that engineered cartilage tissue can grow and mature when implanted into patients with a knee injury. The novel tissue engineering approach can lead to cartilage regeneration even in knees affected by osteoarthritis.
They grew cells extracted from the same persons they implanted cells back into. This approach avoids immune rejection problems.
The tissue engineering method used in this study involved isolating cells from healthy cartilage removed during surgery from 23 patients with an average age of 36 years. After growing the cells in culture for 14 days, the researchers seeded them onto scaffolds made of esterified hyaluronic acid, grew them for another 14 days on the scaffolds, and then implanted them into the injured knees of the study patients.
Cartilage regeneration was seen in ten of 23 patients, including in some patients with pre-existing early osteoarthritis of the knee secondary to traumatic injury. Maturation of the implanted, tissue-engineered cartilage was evident as early as 11 months after implantation.
Antony Hollander, ARC Professor of Rheumatology & Tissue Engineering at Bristol University who led the study, said: "This is the first time we have shown that tissue-engineered cartilage implanted into knees can mature within 12 months after implantation, even in joints showing signs of osteoarthritis.
Initial tissue engineering successes will accelerate the rate of advance of tissue engineering and stem cell therapies. Experience gained from scaling up and automating cell therapy delivery will lead to discoveries for how to refine and improve processes for handling cells. The revenue from stem cell therapy delivery will fund more development.
Although the researchers did not carry out physical tests of the patient’s mobility, these testing techniques have previously been shown to provide a good indicator of the cartilage's function, suggesting movement should be improved too. The reason why not all patients benefited from the engineered cartilage is not yet clear, although Hollander says giving the engineered tissue longer to settle in may help.
The new study is a "textbook example" of how tissue engineering should work, says Julian Chaudhuri, a tissue engineer working on cartilage at Bath University, UK. "Every step is in place from growing the tissue to implanting in patients, and it's been shown to work," he says. "It looks very exciting."
Professor Anthony Hollander and his team at Southmead Hospital have successfully grown human cartilage from a patient's own stem cells for the first time ever.
This means people suffering from the severe form of the bone disease osteoarthritis, which leaves them unable to walk, could in the future have cartilage transplant operations.
Scientists took stem cells from the bone marrow of pensioners undergoing NHS replacement operations because they have arthritis.
They took just over a month to grow the cells into a half-inch length of cartilage.
Stem cell therapy — a technique that relies on the idea that stem cells can be prompted to turn into cartilage cells that will grow and repair damage — is another possible avenue for future treatment. Johns Hopkins researcher Jennifer Elisseeff has used the method in rats, finding that stem cells can fill in holes in the cartilage.
"These cells have the amazing ability to repair parts of the body," says Thomas Vangsness, an orthopedic surgeon at the University of Southern California in Los Angeles.
Vangsness and his colleagues are testing a stem cell therapy developed by Osiris Therapeutics. The Baltimore company has developed a solution of stem cells taken from a single adult donor. Vangsness and his colleagues injected the stem cell solution into the knees of 55 patients with a torn meniscus, cartilage-like tissue in the knee. They're hoping the stem cells will turn into cartilage cells and repair the injury, but the data are just now being analyzed, Vangsness says.
With multiple teams doing human clinical trials the development of successful joint repair using cell therapies no longer seems a distant prospect.
David Gobel, one of the folks behind the Methuselah Mouse Prize, points me to news of an experiment where regular muscle tissue was isolated from rats, shaped into heart tissue that can conduct electric impulses.
Patients with complete heart block, or disrupted electrical conduction in their hearts, are at risk for life-threatening rhythm disturbances and heart failure. The condition is currently treated by implanting a pacemaker in the patient's chest or abdomen, but these devices often fail over time, particularly in infants and small children who must undergo many re-operations. Researchers at Children's Hospital Boston have now taken preliminary steps toward using a patient's own cells instead of a pacemaker, marking the first time tissue-engineering methods have been used to create electrically conductive tissue for the heart. Results appear in the July issue of the American Journal of Pathology (published online on June 19).
The goal of this research is to develop living replacements for artificial pacemakers.
The scienitsts isolated myoblasts, a type of stem cells, from muscles. Then they grew up those cells on a structure made from collagen. The resulting tissue formed a structure implantable on hearts.
Cowan's team, including first author Yeong-Hoon Choi in Children's Department of Cardiac Surgery, obtained skeletal muscle from rats and isolated muscle precursor cells called myoblasts. They "seeded" the myoblasts onto a flexible scaffolding material made of collagen, creating a 3-dimensional bit of living tissue that could be surgically implanted in the heart.
The cells distributed themselves evenly in the tissue and oriented themselves in the same direction. Tested in the laboratory, the engineered tissue started beating when stimulated electrically, and its muscle cells produced proteins called connexins that channel ions from cell to cell, connecting the cells electrically.
The bioengineered tissue created pathways for conducting electricity.
When the engineered tissue was implanted into rats, between the right atrium and right ventricle, the implanted cells integrated with the surrounding heart tissue and electrically coupled to neighboring heart cells. Optical mapping of the heart showed that in nearly a third of the hearts, the engineered tissue had established an electrical conduction pathway, which disappeared when the implants were destroyed. The implants remained functional through the animals' lifespan (about 3 years).
"The advantage of using myoblasts is that they can be taken from skeletal muscle rather than the heart itself--which will be important for newborns whose hearts are so tiny they cannot spare any tissue for the biopsy--and that they're resistant to ischemia, meaning they can go without a good blood supply for a relatively long period of time," Cowan says.
The researchers are now working toward experiments with larger animals.
I like tissue engineering experiments that try to take existing tissue and rearrange it to solve problems. We certainly need advances in understanding of how embryonic stem cells go through series of steps to become much more specialized. However, as demonstrated by this report, not all applications of stem cells require the development of an enormous amount of understanding of how to control the differentiation (specialization) of stem cells through many steps. Existing non-embryonic cells have the potential to be rearranged and grown up into cells needed to solve many medical problems.
MIT bioengineers have devised a new technique that makes it possible to learn more about how cells are organized in tissues and potentially even to regrow cells for repairing areas of the body damaged by disease, accidents or aging.
The method gives them unprecedented control over organizing cells outside the body in three dimensions, which is how they exist inside the body. It uses electricity to move cells into a desired position, followed by light to lock them into place within a gel that resembles living tissue.
Cells traditionally have been studied in two dimensions in a Petri dish, but certain cells behave differently in two dimensions than in three.
"We have shown that the behavior of cartilage cells is affected significantly when they are organized in 3-D," as is the behavior of other types of cells like stem cells, said MIT Associate Professor Sangeeta Bhatia of the Harvard-MIT Division of Health Sciences and Technology (HST), one author of a paper on the technique due to appear in the May issue of Nature Methods.
The new technique is orders of magnitude faster than previous methods used and allows very precise positioning.
The new technique allows for precise control of cell organization, and takes minutes to perform compared to hours or days for the other method.Albrecht and his colleagues have been using a micropatterning technique to carefully position the cells within about 10 microns of each other. That's nearly the diameter of a cell and about one-fifth the diameter of a human hair. The technique uses a device made with photolithography, the same process used to create circuit patterns on electronic microchips.
In the paper, the MIT researchers said they have formed more than 20,000 cell clusters with precise sizes and shapes within a single gel. They have since scaled that up several-fold. They also have created layers of different cells, attempting to mimic the structure of tissue inside the body.
While the technique may one day be applied to engineer tissues for medical applications, its first use will be for basic research on how cells are organized, how they function and communicate in tissues, and how they develop into organs or tumors. The 3-D organization of cells also may help researchers understand how cells respond to drugs when they are in a normal state compared to a diseased state like cancer.
Cars can last much longer than their original design lives because their parts can be replaced repeatedly. Tissue engineering is really all about the development and installation of replacement parts for humans and other animals. Given sufficiently advanced tissue engineering technologies we would not need to die from age-related internal organ failure or suffer from worn out joints or tendons or ligaments. Tissue engineering advances will provide key pieces of the puzzle for how to do full body rejuvenation.
Weekend athletes who overexert themselves running or playing basketball may one day reap the benefits of research at the Hebrew University of Jerusalem that shows that adult stem cells can be used to make new tendon or ligament tissue.
Tendon and ligament injuries present a major clinical challenge to orthopedic medicine. In the United States, at least 200,000 patients undergo tendon or ligament repair each year. Moreover, the intervertebral disc, which is composed in part of tendon-like tissue, tends to degenerate with age, leading to the very common phenomenon of low-back pain affecting a major part of the population.
Until the present time, therapeutic options used to repair torn ligaments and tendons have consisted of tissue grafting and synthetic prostheses, but as yet, none of these alternatives has provided a successful long-term solution.
A novel approach for tendon regeneration is reported in the April issue of the Journal of Clinical Investigation. Researchers Prof. Dan Gazit and colleagues at the Skeletal Biotechnology Laboratory at the Hebrew University Faculty of Dental Medicine engineered mesenchymal stem cells (MSCs), which reside in the bone marrow and fat tissues, to express a protein called Smad8 and another called BMP2.
When the researchers implanted these cells into torn Achilles tendons of rats they found that the cells not only survived the implantation process, but also were recruited to the site of the injury and were able to repair the tendon. The cells changed their appearance to look more like tendon cells (tenocytes), and significantly increased production of collagen, a protein critical for creating strong yet flexible tendons and ligaments.
An advance in imaging technology made it possible to measure and confirm the tendon repair.
Lots of technologies are advancing in ways that support more rapid development of stem cell therapies, gene therapies, and other newer kinds of therapies. The rate of advance of biotechnology will continue to accelerate.
WINSTON-SALEM, N.C. -- The first human recipients of laboratory-grown organs were reported today by Anthony Atala, M.D., director of the Institute for Regenerative Medicine at Wake Forest University School of Medicine. In The Lancet, Atala describes long-term success in children and teenagers who received bladders grown from their own cells.
“This is one small step in our ability to go forward in replacing damaged tissues and organs,” said Atala, who is now working to grow 20 different tissues and organs, including blood vessels and hearts, in the laboratory.
The engineered bladders were grown from the patients’ own cells, so there is no risk of rejection. Scientists hope that laboratory-grown organs can one day help solve the shortage of donated organs available for transplantation. Atala reported that the bladders showed improved function over time -- with some patients being followed for more than seven years.
The study involved patients from 4 to 19 years old who had poor bladder function because of a congenital birth defect that causes incomplete closure of the spine. Their bladders were not pliable and the high pressures could be transmitted to their kidneys, possibly leading to kidney damage. They had urinary leakage, as frequently as every 30 minutes.
The success is the culmination of an idea that the team began exploring 16 years ago. Atala adds that they are also working on growing bio-engineered hearts and pancreases in the lab.
Why can old cars run for decades longer than their original design? Because when their parts break they can be replaced. Same will be true for humans. This isn't a distant science fiction fantasy. Growth of replacement organs will become very commonplace in the first half of the 21st century.
Update: The cost of growing the bladder is $4000 per patient (though the New York Times quotes an even higher figure of $7000). That doesn't include the cost of the surgery to implant it or other fees for doctors. The bladder grows on a scaffold.
To grow new bladder tissue, his team biopsied cells from the muscle and lining of the bladder walls in individual patients. These cells were cultured in the lab, then seeded onto a specially constructed, biodegradable mould, or scaffold, shaped like a bladder.
Over the next two months, the cells continued to grow into the mould, which was then sutured to the patient's original bladder. (The mould degrades as the bladder tissue integrates with the body.)
Cost is a big problem, especially since all the organs age and will need either replacement or rejuvenation in place. The ability to grow replacement organs in pigs genetically engineered to have many human genes will some day greatly lower the costs of making replacement organs..The work of genetically engineering pigs for this purpose ought to receive much higher levels of funding.
Stem cell therapies, gene therapies,and assorted nanotech devices will eventually provide the means to repair and rejuvenate organs in place.
Dr. Atala added that 80 researchers in his regenerative medicine institute at Wake Forest were trying to apply the scaffolding techniques to build new hearts, livers, kidneys, pancreases, nerves and other tissues.
The huge historical turning point where human bodies become repairable is within sight.
Rodents blinded by a severed tract in their brains' visual system had their sight partially restored within weeks, thanks to a tiny biodegradable scaffold invented by MIT bioengineers and neuroscientists.
This technique, which involves giving brain cells an internal matrix on which to regrow, just as ivy grows on a trellis, may one day help patients with traumatic brain injuries, spinal cord injuries and stroke.
The study, which will appear in the online early edition of the Proceedings of the National Academy of Sciences (PNAS) the week of March 13-17, is the first that uses nanotechnology to repair and heal the brain and restore function of a damaged brain region.
"If we can reconnect parts of the brain that were disconnected by a stroke, then we may be able to restore speech to an individual who is able to understand what is said but has lost the ability to speak," said co-author Rutledge G. Ellis-Behnke, research scientist in the MIT Department of Brain and Cognitive Sciences. "This is not about restoring 100 percent of damaged brain cells, but 20 percent or even less may be enough to restore function, and that is our goal."
Spinal cord injuries, serious stroke and severe traumatic brain injuries affect more than 5 million Americans at a total cost of $65 billion a year in treatment.
Biotech will eventually lead to massive savings aind increased productivity as many disabling diseases and disorders become curable.
Self-assembling peptides (amino acids in polymers) were key to this achievement.
Shuguang Zhang, associate director of the CBE and one of the study's co-authors, has been working on self-assembling peptides for a variety of applications since he discovered them by accident in 1991. Zhang found that placing certain peptides in a salt solution causes them to assemble into thin sheets of 99 percent water and 1 percent peptides. These sheets form a mesh or scaffold of tiny interwoven fibers. Neurons are able to grow through the nanofiber mesh, which is similar to that which normally exists in the extracellular space that holds tissues together.
The process does not involve growing new neurons, but creates an environment conducive for existing cells to regrow their long branchlike projections called axons, through which neurons form synaptic connections to communicate with other neurons. These projections were able to bridge the gap created when the neural pathway was cut and restore enough communication among cells to give the animals back useful vision within around six weeks. The researchers were surprised to find that adult brains responded as robustly as the younger animals' brains, which typically are more adaptable.
The injected peptides self-assemble when they come into contact with fluid that bathes the brain.
When the clear fluid containing the self-assembling peptides is injected into the area of the cut, it flows into gaps and starts to work as soon as it comes into contact with the fluid that bathes the brain. After serving as a matrix for new cell growth, the peptides' nanofibers break down into harmless products that are eventually excreted in urine or used for tissue repair.
The MIT researchers' synthetic biological material is better than currently available biomaterials because it forms a network of nanofibers similar in scale to the brain's own matrix for cell growth; it can be broken down into natural amino acids that may even be beneficial to surrounding tissue; it is free of chemical and biological contaminants that may show up in animal-derived products such as collagen; and it appears to be immunologically inert, avoiding the problem of rejection by surrounding tissue, the authors wrote.
The researchers are testing the self-assembling peptides on spinal cord injuries and hope to launch trials in primates and eventually humans.
Some day severe spinal cord injuries will not condemn people to spend the remainder of their lives in wheelchairs.
Schneider estimates that 30,000 axons had reconnected, compared with only around 30 in previous experiments using other approaches, such as nerve growth factors. The team speculates that the similarity between the size of the fibres and the features on neural material is what encourages the axons to bridge the gap. The scaffold appears to eventually break down harmlessly.
Bioengineering is taking off. Some advances such as the one above are measured in orders of magnitude differences as compared to what was possible previously. This is why I'm optimistic that reversal of the aging process is within a few decades reach.
University College London researcher Robert Brown and his team have stumbled upon a cell free way to rapidly produce collagen protein polymers for surgical repair of collagen damage.
A research team from the UCL Tissue Repair and Engineering Centre (TREC), the UCL Eastman Dental Institute and the UCL Institute of Orthopaedics, have pioneered a novel technique for engineering tissues, which has the capacity to greatly reduce the time taken to fabricate implantable human tissue.
Tissue engineering is a method whereby the patient has cells extracted from his or her body and grown under laboratory conditions for a myriad of applications such as cartilage, skin grafts, heart valves and tendons, without the risk of rejection, infection or the ethical dilemma involved in transplanting a donated organ.
Current tissue engineering methods depend on the ability of the cultured cells themselves to grow new tissue around a cell scaffold, which is slow, expensive and has limited success. Professor Brown’s process is cell-independent, controlled engineering of scaffolds by rapidly removing fluid from hyper-hydrated collagen gels.
The fluid is removed by employing plastic compression, a process that the team found produces dense, cellular, mechanically strong collagen structures that can be controlled at nano and micro scales and which mimic biochemical processes.
Principal investigator Professor Robert Brown (UCL TREC) said: “The fluid removal dramatically shrinks the collagen by well over 100 times its original volume, which provides the ability to introduce controlled mechanical properties, and tissue-like microlayering, without cell participation. Crucially, this takes minutes instead of the conventional days and weeks without substantial harm to the embedded cells. The rapidity and biomimetic potential of the plastic compression fabrication process opens a new route for the production of biomaterials and patient-customised tissues and represents a new concept in ‘engineered’ tissues.”
A paper describing the process in detail will be published in the October edition of the ‘Advanced Functional Materials’ journal.
Cell-seeded collagen gel typically takes weeks to develop into weak, early-stage tissues. In the UCL study, published today in Advanced Functional Materials online, the team sucked most of the water out of the structure in a procedure known as plastic compression rather than waiting for the cells to do their job.
The result - following huge-scale shrinkage by a factor of at least 100 - was a simple collagen-based tissue created in 35 minutes. The shrinkage – a new approach to microfabrication – also gave the tissue an average break strength of 0.6 MPa (megapascals) compared with tissues conventionally grown over 1 to 12 weeks of around 0.3 MPa. Given that collagen sheets are fragile – in the study they were around 30 micrometres thick – the team rolled them up like swiss rolls to produce 3D rods which were easier to handle and manipulate.
Tissue engineering typically involves placing cells on a polymer scaffold and allowing them to grow into the desired tissues, which can then be used for surgical implantation. The process can take days or weeks and is difficult to control, cells may also fail to develop into the target material and at best, produce a tissue of less than 1 MPa break strength compared with natural collagen which can be up to 100 MPa strong in a human tendon.
Collagen makes up a quarter of the body.
Collagen is a protein which acts as a structural support for skin, bone, tendon, ligament, cartilage, blood vessels and nerves and as such it makes up 25 per cent of the human body.
Collagen accumulates damage with age and injury just like the rest of the body. So the ability to produce collagen quickly for implant is another step down the road toward full body rejuvenation. However, since collagen's arrangement in so many locations in the body is so microscopic in structure and in so many different locations surgery is not a practical method of replacing all or even most worn collagen. A lot of the damaged collagen in an aged body will need to be replaced by cells sent into the body as cell therapy programmed to do collagen repair. Still, this latest discovery has uses for repair of larger sized pieces of collagen.
The discovery was made accidentally.
Professor Robert Brown, of the UCL Institute of Orthopaedics, says: “We stumbled across this discovery while trying to measure the compression properties of collagen gel. Our method offers a simple and controllable means of quickly engineering tissue structures. The next stage is to test whether this method could help repair injured tissues.
“The speed and control it offers means that our method could one day be used to produce implant tissue at the bedside or in the operating theatre. We have a proof of concept grant from UCL BioMedica to produce a semi-automatic device for implant production. Ultimately, the goal is to design a rapid, inexpensive, automatic process for creating strong tissues which could supply hospital surgical units with a tool kit of spare parts for reconstructive surgery.”
This result fits a larger pattern of bioscientific and biotechnological advances where smarter manipulation of biological molecules allows processes to be speeded up by orders of magnitude.