October 28, 2005
Cytokines Stimulate Stem Cells To Heal Heart Attack Patients?
Heart specialist Sebastiano Marra at Turin University in Italy found that injection of cytokine hormones into the body after a heart attack marshals stem cells to repair the heart and leads to better outcomes.
In the new technique, hormones called cytochines are injected into the body during the 24 hours after emergency heart surgery and immediately spur the production of stem cells in spinal fluid.
The stem cells race to rescue the damaged heart, Marra said.
"The acute inflammation of the heart attracts the stem cells whose role in the body is to repair cardiac tissue," said Marra, who operated on the patients at Turin's Molinette Hospital.
Tests on eight patients who were operated on immediately after a heart attack have produced "amazing" results, he said.
"They were soon back on their bicycles or going to swimming pools." Compared to experimental methods used so far, the Turin technique is far less invasive, Marra continued.
Mind you, this is a news report on only 8 patients and not a journal article with a larger number of patients with controls and a detailed comparison of outcomes. Still, the approach is at least plausible. Stimulation of the production of stem cells is already used to make stem cells from donors to treat leukemia. But Marra is trying to stimulate stem cells within the same body that needs them for heart muscle repair.
The technique might work less well in the really old because stem cell reservoirs in older people are aged and do not divide as quickly. However, one study found that elements in the blood of the old mice caused their stem cells to grow less rapidly. So it isn't so much that the stem cells are old but that they are getting signals telling them not to grow. Perhaps cytokines or other compounds can override those suppressor signals. So Marra's approach might work even for old folks.
Thanks to Brock Cusick for the pointer.
Interesting study - I wonder which cytokine(s) they used, whether they also tried growth factors, and what studies in mice (or other animal models) they based this human study on.
So what happens to those stem cells if they arenít attracted to wound sites? Do they just continue to circulate in the blood? Are they attracted to sites with old damage? Would they go to the lesser wounds that occur as part of the normal wear and tear of life?
What would happen if we continually stimulated increased stem cell production? Would our tissues grow younger? Would our stem cell reservoirs age faster? Would we increase our cancer rates?
What if we periodically stimulated stem cell increases?
Do we need to provide the correct growth factors so that the stem cells will be partially differentiated to target the tissues that we desire repaired?
Surely someone is doing these experiments in mice.
I do not know the answer to all your questions. However, a couple of points about cytokines:
1) Something called a "cytokine storm" is suspected of contributing to death from some infections. For example, the 1918 influenza might have triggered a "cytokine storm" and caused an excess inflammation reaction that helped cause the lungs to fill with fluid. Scientists fear the current H5N1 avian flu might be doing the same.
2) Chronic inflammation (partly due to infection and partly due to other causes) can cause disease and bodily decay. Cytokine administration over the long term would probably cause the chronic inflammation and disease.
3) Chronic inflammation is correlated with more worn down telomeres. I think I have done a post or two about this.
Therefore continual dosing with cytokines is probably a bad idea.
To the subject of the post: What we really need are treatments that prevent the heart attack in the first place. But that is harder to do with cytokines because there is not as loud of a damage signal coming from the heart before the heart attack.
For anyone wanting more details on cytokine action, the link below will help. Cytokines tend to interact with each other and can inhibit or augment the other's action. Critical care medicine specialists have much to gain from understanding this topic, as do all clinicians and medical researchers.
This is the source for the paragraph below.
The central role in inflammatory responses have IL-1 and TNF-, because the administration of their antagonists, such as IL-1ra (IL-1 receptor antagonist), soluble fragment of IL-1 receptor, or monoclonal antibodies to TNF- and soluble TNF receptor, all block various acute and chronic responses in animal models of inflammatory diseases. Some of these antagonists are beginning to utilize as anti-inflammatory agents in diseases such as sepsis and rheumatoid arthritis. IL-1 and TNF- together with IL-6 serve as endogenous pyrogens. The up-regulation of inflammatory reaction is also performed by IL-11, IFN- , IFN- , and especially by the members of chemokine superfamily. On the other hand, anti-inflammatory cytokines (IL-4, IL-10, IL-13) are responsible for the down-regulation of inflammatory responses. They are able to suppress the production of proinflammatory cytokines. Their strong anti-inflammatory activity suggest possible utilization in management of many inflammatory diseases, including sepsis, rheumatoid arthritis, inflammatory bowel disease, psoriasis, T cell-mediated autoimmune diseases such as type I diabetes, as well as in acute graft-versus-host disease. IL-10 is capable of effectively protecting mice from endotoxin-induced shock, a lethal inflammatory reaction mediated by TNF- and IL-1. The production of most lymphokines and monokines such as IL-1, IL-6 and TNF- is also inhibited by transforming growth factor (TGF- ). But, on the other hand, TGF- has a number of proinflammatory activities including chemoattractant effects on neutrophils, T lymphocytes, and unactivated monocytes. TGF- has been demonstrated to have in vivo immunosupressive and anti-inflammatory effects as well as proinflammatory and selected immunoenhacing activities. When administered systemically, TGF- acts as an inhibitor, but if given locally can promote inflammation.
Imagine you have had a heart attack, and your doctor tells you to take it easy, take all the meds, you can't fully function and you are afraid of another heart attack.
Now, imagine your doctor tells you that you can bring your dead heart tissue back to life or grow new heart tissue. Wow. That is the import of this work.
Direct cytokine administration to the heart for cardiac regeneration is the wave of the future. G-CSF is a cytokine used to mobilize progenitor cells from bone marrow, and has been used to mobilize stem cells for cardiac regeneration. Stem cells aren't necessary, although a number of companies would like to sell complicated equipment for isolating stem cells and infusing them into the heart.
Apparently cardiac stem cells exist in pockets in the heart already. http://physrev.physiology.org/cgi/content/abstract/85/4/1373 So mobilization isn't necessary, apparently --just drum up the stem cells in the pockets in the heart already.
A new study reports a protein released by damaged or dead cells High-mobility group box 1 protein (HMGB1)appears to be the key to local stem cells in the heart. http://circres.ahajournals.org/cgi/content/abstract/97/8/e73 This produces new cells having the c-kit (stem cell factor) receptor. Likely stem cell factor or granulocyte colony stimulating factor will promote growth once the local stem cells start expressing those receptors.
It looks like the signal protein (HMGB1) in combination with SCF or G-CSF will result in myocardial regeneration.
This may be one of the grand payoffs from biotech research stimulated by discoveries in genetic engineering in the 1970s further boosted by big money research into AIDS immunology in the 80s and 90s. The really big payoffs are coming.
Circulation. 2005 Aug 30;112(9 Suppl):I73-80.
BACKGROUND: Experimental and clinical evidence has recently shown that pluripotent stem cells can be mobilized by granulocyte colony-stimulating factor (G-CSF) and may enhance myocardial regeneration early after primary percutaneous coronary intervention (PCI) management of acute myocardial infarction. Sustained or long-term effects of mobilized CD34-positive mononuclear stem cells, however, are unknown. METHODS AND RESULTS: Thirty consecutive patients with ST-elevation myocardial infarction undergoing primary PCI with stenting and abciximab were selected for the study 85+/-30 minutes after PCI; 15 patients were randomly assigned to receive subcutaneous G-CSF at 10 microg/kg body weight for 6 days in addition to standard care including aspirin, clopidogrel, an angiotensin-converting enzyme inhibitor, beta-blocking agents, and statins. In patients with comparable demographics and clinical and infarct-related characteristics, G-CSF stimulation led to sustained mobilization of CD34 positive mononuclear cells (MNC(CD34+)), with a 20-fold increase (from 3+/-2 at baseline to 66+/-54 MNC(CD34+)/microL on day 6; P
I have been taking Granocyte injections for my heart for several years now. I can tell you from blood tests that it boosts white cells including stem cells many fold. It does have some flu like side effects and some bone pain, but it is short lived and usually very mild.
My condition has improved but the best time to get this treatment is directly after a heart attack when the homing chemicals are being sent out by the heart as the previous email discribes. Dr. Sibia in India can set you up with the injections like he did me. My first experience was in Moscow with a immunology professor who introduced me to Granocyte and said it was worth a try as I was going downhill quick. They first offered bypass but as I told them my distal ends and mid vessels are occluded all over the heart so a bypass was not feasible.
I review in detail all my angiograms and don't leave a hospital without the disk or tape. Granocyte has no known long term adverse side effects as it is naturally produced in the body in much smaller quantities. It is used to boost the immune system after chemotherapy and radiation for cancer so you should know it doesn't cause cancer. I could go on and on but there is a vast amount of information on the net like has been presented by others here. The trick is to put all the pieces together to stimulate not only the production of stem cells but the effective division of those in circulation and those already in the heart.
I think ECP and EECP effectively does the same thing by increased blood flow in the marrow as well as the heart. Dr. Sibia in India also has a superior Ecp machine that was designed in China which also incorporates arm cuffs to keep the blood in the central body. It would be nice if they had a neck cuff as well but that would be rather hard on the patient.
Also of interest is that fact that a doctor and electronic engineer in India has invented a Magnetic Resonate Machine which works on the MRI principle to change the cell membrane potential to cause cell division. They are curing knee joint and bypassing surgery and knee replacements with this machine and he designed it for hearts. Dr. Sibia has one on the way to him at this time. The doctor chose knee joints first because it turned out to be a easy task and it worked. I read the book and the theory upon which it works while in Ludihana doing ECP, Granocyte and other therapies. I believe this machine and those latent stem cells in the heart can resonated to divide. The cell membrane research reveals that a healthy stable cell exhibits a membrane potential of -60 to -100mv. To get the cell to divide that membrane potitential is raised to -15mv. After cell division the cell will return to resting potentional.
Cytoplasmic Membrane Potentials
Healthy cells -70mv
Infected -40 to -60mv
Cancer -20 to -30mv
You will find the above cell voltage documented on the internet but I haven't found anything yet on the machine which is relatively new and to my knowlege only found in India.
Rotational Field Quantum Nuclear Magnetic Resonanace by Dr. R V Kumar
Dr. Sibia is located in Ludihana, India and has a web page on the net which you can find with a search. His email address is sssibia.com and he is a member of my ECP group as well. Tell him Clyde sent you. If you are a interested in the above book, he may be able to obtain a copy for you or have his book scanned or OCR scanned for you. That is something I should have done while I was there and if I go again, I will do it, although most of the theory has been known for years and is on the net. The information relevant to the machine itself is not available except from India. It looks like a big wheel with a movable bed running through the center of the ring. The ring contains the magnetic guns which focus magnetic resonate fields to the target area.
Just don't go there in the Summer like I did, it is hotter than hell. 42-45C is not my temperature and I don't run with elephants in that heat.
Interesting post. Nowadays he hear more and more info every day about the use of stem cells. One such I read in "The washington Times" about Stem Cells Can Aid Spinal Disc Repair
This is going to be a real hope, of an effective new treatment for the many sufferers of low back pain.