Stem Cell Banks Envisioned for Regenerative Medicine
News Nov 30, 2012
Stem cell “banks” could serve as a valuable resource for emerging treatments in the field of regenerative medicine, though challenges remain to making them a reality, according to a panel of international experts who gathered at UCSF for a stem cell conference last month.
Funding for the development of stem cell lines for research has long been subject to debate, especially before President Barack Obama lifted a Bush-era ban on federal funding in 2009, but now scientists are discussing how to best meet the anticipated need for stem cells for medicine as well as research.
Stem cell treatments developed from adult cells rather than from embryonic tissue are expected to enter clinical trials for macular degeneration in Japan next year, and early successes in such trials aimed at replacing damaged tissues would be expected to drive demand for such stem cells upward. Worldwide, stem cell scientists in academia, government and the private sector are gauging strategies for moving forward with stem cell banks to meet expected demand.
So far, countries have been taking different paths toward acquiring these resources, panelists said at an Oct. 25 discussion at the International Society for Stem Cell Research conference held at the UCSF Mission Bay campus.
Panelists for the discussion, titled “Challenges and Opportunities in Cellular Reprogramming,” included Shinya Yamanaka, MD, PhD, a UCSF professor of anatomy senior investigator with the UCSF-affiliated Gladstone Institutes who won the 2012 Nobel Prize for Physiology or Medicine for discoveries that are the groundwork for many of today’s regenerative medicine strategies.
Yamanaka, who is also director of the Center for iPS Cell Research and Application at Kyoto University, has advocated stem cell banking for medicine in his native Japan, where the government recently made a commitment to begin stem cell banking.
Yamanaka pioneered the use of induced pluripotent stem (iPS) cells, which are created when individuals provide skin cells or other easily obtained cells that scientists then reprogram in the lab to become virtually any cell type. One of primary advantages to iPS cells is that their use overcomes ethical objections to the use of embryonic stem cells, which are developed from leftover embryos obtained from in vitro fertilization clinics.
Because iPS cells can be created from the cells of individuals afflicted with specific diseases, they can be used to develop new disease models to learn more about how diseases arise and how they might be treated. But in addition, panelists emphasized, iPS cells can be reprogrammed to become long-lived stem cells specialized for particular organs and tissues and play a role in treatments now being developed for regenerative medicine.
“Our effort in Japan is to establish iPS stocks for regenerative medicine,” Yamanaka said.
Individualized Treatment vs. Stem Cell Banks
In principle, the capability to use a patient’s own cells to derive individualized treatment also would be expected to avoid the threat of immune rejection posed by tissue transplants from others. However, the cost and time required to produce individualized treatment may pose a practical barrier for medical practice.
An alternative strategy is to create a sufficient number of cell lines to provide a suitable match for the population to be served.
In the same way that organ transplant recipients are matched with living donors with compatible immune systems through a process known as human-leukocyte-antigen (HLA) matching, scientists are hopeful that cell lines needed to immunologically match all recipients can be created and maintained for use when needed.
A committee of the Japanese health ministry recently granted a go-ahead for the development of cell lines from thousands of fetal umbilical blood samples, as part of the iPS Cell Stock project that Yamanaka is promoting in that country. Yamanaka aims to maintain the cell lines for use in medicine.
“What we are now planning is to establish HLA-matched banks of iPS cells … but we don’t yet how beneficial it will be to match HLA,” Yamanaka said. “I believe that we will still need immunosuppressants, but I am hoping that by matching HLA, we can at least reduce the amount of immunosuppressants, so that we can reduce side effects and increase the survival rate.”
Transplant Rejection Advances
In the United States, the National Institutes for Health (NIH) Center for Regenerative Medicine and NIH Clinical Center have developed guidelines for obtaining informed consent for iPS cell-based research and therapies, and aim to establish standards for creating cell lines for medicine.
However, stem cell banks aren’t yet being developed in this country, according to panelist Mahendra Rao, MD, PhD, the head of the NIH Center for Regenerative Medicine. “Currently the NIH is not looking at therapeutic banks of the kind that people have proposed in Japan or Europe,” Rao said.
HLA matching is unlikely to solve all of the immune rejection issues that may arise with stem cell transplantation, Rao explained, but new strategies being developed to prevent transplant rejection may prove applicable to cells derived through iPS techniques. “There are lots of other technologies that people are considering that could be an important complement,” he said.
Panelist Irving Weissman, MD, from the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University School of Medicine, said that he has been able to demonstrate a promising strategy for preventing transplant rejection in his own work.
Weissman, a leading expert on hematopoietic stem cells – the cells responsible for regenerating the blood and immune system in bone marrow transplants – said that by temporarily disabling the immune system of the transplant recipient and transplanting hematopoietic stem cells along with the needed organ, it is possible to eliminate immune cells from the recipient that, if present, would cause transplant rejection. The strategy should work with tissue stem cells as well as with organ transplants, he said.
“The stem cells give rise to the cells that delete reactive immune cells [made by the recipient’s immune system] against any tissue or organ from that donor,” and can be used to avoid the need for lifelong immunosuppression, according to Weissman.
Stem Cell Donor Selection
Moderator Bruce Conklin, MD, a Gladstone senior investigator and a UCSF professor of medicine, asked panelists how feasible it was to develop a panel of iPS cell lines could serve the needs of such an ethnically and genetically diverse U.S. population.
Weissman noted that clients of in vitro fertilization clinics who provide the cells used to derive embryonic stem cell lines tend to be much less ethnically diverse than the general population.
But to develop iPS cells, “You can go get a check swab, make the cell line, and now start to set up what you need,” he said. “I think it’s the real future of regenerative medicine when we get to that stage.”
Conklin posed another donor question: Who would be the healthiest donors of cells to create cell lines for banking?
“When I get my stem cell transplant, I want it from cells and a genome that has been road tested,” he said. “I would prefer to have someone who is in the senior Olympics – someone who is 95 years old and completely healthy.”
Alternatively, Conklin wondered, would it be better to select young donors whose health histories had not yet been written. Panelists acknowledged that this remains an open question.
Conklin also suggested that as donors had their genomes sequenced, it would reveal dozens of defective genes, as all humans possess genetic imperfections. So what criteria would result in donors being turned away because of mutations in their genomes?
Weissman countered that the many questions slowing the decision-making about stem cell banking could be coming at a high cost.
“If you don’t start, you’ll never get there,” he said. “It’s good to be conservative, and it’s good to be cost-effective, but just think of the cost of these devastating diseases for which there are no cures.”
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