Technology Review has a good review article on various efforts to use cells grown in mechanical devices to create temporary organ replacements for kidneys, livers,
“Patients who are undergoing chronic dialysis become malnourished, and they sort of wither,” says Harmon. The solution, believes Humes, lies in harnessing kidney cells themselves—cells that can rapidly react to changes in the body’s environment in a way that machines simply can’t.
The kidney-in-a-cartridge, which is being developed by Lincoln, RI-based University of Michigan spinoff Nephros Therapeutics, could be ready for widespread use in as little as three years. And it’s only one example of the increasingly popular strategy of using living cells to do the heavy lifting in artificial organs. Several academic labs are developing similar devices packed with liver cells to chew up the toxins that accumulate in the blood when the liver suddenly fails. Already in human trials, these bioartificial livers could help patients in acute liver failure, whose only chance today is a rare organ transplant.
Nephros Therapeutics, Inc. announced today the successful completion of a Series C financing totaling $17 million to accelerate the clinical development of its lead product, the Renal Assist Device (RAD). Based on patented renal stem cell technology licensed from the University of Michigan and invented by Dr. H. David Humes, Nephros is developing the RAD for the potential treatment of Acute Renal Failure (ARF). Lurie Investments of Chicago, IL led the financing round. New investors participating in this round include CDP Capital of Montreal, QC, as well as Foster & Foster of Greenwich, CT. All of Nephros’ existing investors, including BD Ventures, Portage Venture Partners, North Coast Technology Investors, Palermo Group (an affiliate of the Apjohn Group), and the founding investor, Seaflower Ventures, also participated in this round.
Nephros’ Renal Assist Device (RAD) is a cellular replacement therapy system that leverages the Company’s proprietary Renal Proximal Tubule (RPT) cell technology for the potential treatment of ARF patients. RPT cells play a key role in the regulation of response to inflammation and stress and are critical to normal kidney function and the patient’s ability to fight infection. Nephros has established pioneering technologies to isolate and expand (ex vivo) kidney-derived stem cells and to then create delivery systems. In contrast to the limitations associated with current replacement therapy (e.g. hemodialysis), the RAD’s RPT therapy is being investigated for the potential to replace and maintain a full range of key functions of the kidney, including endocrine equilibrium, metabolic activity and immune surveillance. Nephros is currently supporting two Phase I/II physician-sponsored clinical trials for RAD, at the University of Michigan and the Cleveland Clinic, for the potential treatment of ARF.
David Humes, M.D., Professor of Internal Medicine at the University of Michigan has worked for a decade to develop the bioartificial kidney that is going thru clinical trials.
A bioartificial kidney device invented by Dr. Humes is being clinically evaluated for treatment of patients in acute renal failure. Phase II human trial of the device has been approved by FDA and is expected to commence in the Fall of 2003.
The same core technology using adult kidney stem cells will be soon be tested in a device designed to ameliorate hyperinflammation associated with End Stage Renal Disease. Hyperinflammation may lead to infections and cardiovascular problems, leading causes of early death in chronic renal failure patients.
No volunteers are needed for either of these studies.
Phase I trial recently concluded on the device for treating acute renal failure was led by principal investigator Robert Bartlett and co-investigators William (Rick) Weitzel and Fresca Swaniker in Ann Arbor and by Emil Paganini in Cleveland. The initial study demonstrated that the device is safe for further testing. The next investigations will measure the treatment's effectiveness. Published results, as they become available, will be added to the link at the bottom of this page.
Acute renal failure is a sudden onset of kidney failure brought on by accident or poisoning. Unlike chronic renal failure, acute renal failure is potentially reversible, if the patient can be sustained through the episode. Most cannot. The mortality rate of ARF is greater than 50%.
The poor survivability of ARF appears to be linked to the loss of certain functions of the kidney that reside in cells called renal proximal tubule (RPT) cells. The RAD conceived by Dr. Humes contains living human renal proximal tubule cells. In large animal studies [reported in the journal Nature Biotechnology (April 30 1999)], the Humes lab demonstrated that the cells in the RAD perform the metabolic and hormonal functions lost in ARF. Restoring these critical functions by use of the RAD may be key to helping patients survive acute renal failure.
Because the RAD contains living human tissue it is termed a bioartificial kidney.
Initial trials with patients suffering from acute kidney failure were more successful than expected probably because the bioartifiical kidney cells released chemical messengers that suppressed an immune response that was damaging the kidneys of the patients experiencing kidney failure.
In early clinical trials at the University of Michigan, a bioartificial kidney has been used in a handful of intensive-care patients who were deemed very likely to die because kidneys and other organs were failing. All but one recovered with normal kidney function.
Also see this previous post entitled Device Maintains External Liver Cells For Blood Filtration.
Current purely artificial kidney dialysis machines do only a subset of what a real kidney does and there is a clear need for functionally richer replacement devices. Bioartificial livers and kidneys which use living cells are going to reach the market well before fully functional purely artificial versions of those same organs are ready. In large part this is because we do not know all the functions that livers and kidneys carry out. Best to use cells that know how to do all the functions while scientists try to figure out how those organs work in greater detail.
Complete organs grown to replace diseased organs are also further into the future than bioartificial devices. The tissue engineering problems involved in growing complete organs are also a lot tougher to solve than problems involved in growing cells in artificial apparatuses. My guess is that for more complex organs such as the liver and the kidney the ability to grow replacement organs will be achieved many years before the ability is developed to build a totally artificial organ that carries out all the functions that the real organs do.
|Share |||Randall Parker, 2003 July 02 02:21 AM Biotech Organ Replacement|