Posted on 07/21/2009 2:28:31 PM PDT by neverdem
In a proof-of-concept study, Mayo Clinic investigators have demonstrated that induced pluripotent stem (iPS) cells can be used to treat heart disease. iPS cells are stem cells converted from adult cells. In this study, the researchers reprogrammed ordinary fibroblasts, cells that contribute to scars such as those resulting from a heart attack, converting them into stem cells that fix heart damage caused by infarction. The findings appear in the current online issue of the journal Circulation.
"This study establishes the real potential for using iPS cells in cardiac treatment," says Timothy Nelson, M.D., Ph.D., first author on the Mayo Clinic study. "Bioengineered fibroblasts acquired the capacity to repair and regenerate infarcted hearts."
This is the first application of iPS-based technology for heart disease therapy. Previously iPS cells have been used on only three other disease models: Parkinson's disease, sickle cell anemia and hemophilia A. The ultimate goal is to use iPS cells derived from patients to repair injury. Using a person's own cells in the process eliminates the risk of rejection and the need for anti-rejection drugs. One day this regenerative medicine strategy may alleviate the demand for organ transplantation limited by donor shortage, the researchers say.
"This iPS innovation lays the groundwork for translational applications," comments Andre Terzic, M.D., Ph.D., Mayo Clinic physician-scientist and senior author. "Through advances in nuclear reprogramming, we should be able to reverse the fate of adult cells and customize 'on demand' cardiovascular regenerative medicine."
From Damage to Repair
The Mayo Clinic team genetically reprogrammed fibroblasts via a "stemness-related" human gene set to dedifferentiate into an iPS cell capable of then redifferentiating into new heart muscle. When transplanted into damaged mouse hearts, iPS cells engrafted after two weeks, and after four weeks significantly contributed to improved structure and function of the damaged heart, in contrast to ineffective ordinary fibroblasts.
Compared to non-engineered fibroblasts, the iPS cells:
-- Restored heart muscle performance lost after the heart attack
-- Stopped progression of structural damage in the damaged heart
-- Regenerated tissue at the site of heart damage
The Mayo research team included Almudena Martinez-Fernandez, Pharm.D.; Satsuki Yamada, M.D., Ph.D.; Carmen Perez-Terzic, M.D., Ph.D.; and Yasuhiro Ikeda, D.V.M., Ph.D.; along with Lois Rowe and Jonathan Nesbitt. The research was supported by the National Institutes of Health, American Heart Association, American Society for Clinical Pharmacology and Therapeutics, National Hemophilia Foundation, La Caixa Foundation Graduate Program, Marriott Individualized Medicine Program, Marriott Heart Disease Research Program, and Mayo Clinic.
About Mayo Clinic
Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. Doctors from every medical specialty work together to care for patients, joined by common systems and a philosophy of "the needs of the patient come first." More than 3,300 physicians, scientists and researchers and 46,000 allied health staff work at Mayo Clinic, which has sites in Rochester, Minn.; Jacksonville, Fla.; and Scottsdale/Phoenix, Ariz. Collectively, the three locations treat more than half a million people each year.
Source: Mayo Clinic
Article URL: http://www.medicalnewstoday.com/articles/158152.php
Main News Category: Heart Disease
Also Appears In: Cardiovascular / Cardiology, Stem Cell Research,
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It looks like someone change the title.
regenerative medicine ping
Another point for adult stem cells (even adult induced pluripotent cells).
Embryonic stem cells still zero.
Have you looked into the methods by which iPS are “induced”? The method involves introducing a retrovirus-based vector containing the “human stemness factors”. Besides the retrovirus (HIV is a retrovirus, the strain of retrovirus used for these vectors is not derived from HIV, but some of the features that make HIV such a difficult disease to eradicate remain), one of the “human stemness factors” is a gene known to be activated and to participate in the evolution of cancer.
Adult stem cells that are currently in use in FDA-approved clinical trials are not genetically manipulated. The range of cell types that adult stem cells can produce is also limited - often to just a single cell type. This provides a safety factor for recipient patients that neither iPS nor ESC can achieve today.
A few excerpts from the whole article that are interesting when considering the product development potential of iPS.
1) These studies were done in MICE, not humans
2) HIV sequences were in fact used in the vector to generate iPS, “The packaging plasmid, pCMVR8.91, was engineered with H87Q mutation in the HIV-1 capsid region for increased transduction efficiency of purified infectious supernatants.” Would you want yourself or a loved one treated with cells containing portions of the HIV that facilitate the stable integration (i.e., copies of the virus DNA are made every time any recipient cell divides) of virus DNA with cellular DNA?
3)Discrepancy between the timing of treatment and the time required to make product. The iPS took a minimum of 4 weeks to produce. The mice were injected with iPS within 30 minutes of a surgically-induced state of myocardial ischemia. How could a human be treated with autologous (made from the person’s own cells, which is one of the big selling points of iPS) iPS within 30 minutes if it takes more than 4 weeks to produce them?
4)Discrepancy between the disease MODEL treated and real human disease. These mice were perfectly healthy just before the short surgery used to generate the ischemia in the heart. Human disease occurs over long periods of time and patients who might qualify for such treatments have damage from long-term ischemia. Acute conditions such as those being “treated” in these studies on iPS will often self-correct over time. The iPS may shorten the healing timeframe by a few days or weeks, but is that a sufficient incentive to pay the cost of iPS vs. standard of care?
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