Stem cell therapy has the potential to transform medicine from mostly just treating symptoms to restoration of healthy, youthful tissue following every injury, disease, and age-associated degeneration. Unfortunately, along with such great hope has come scientific fraud,1,2 ethical questions,3 and a host of other controversies. The federal ban placed on stem cell research in 2001 has markedly delayed the introduction of this breakthrough therapy into clinical practice application.
Stem cells vary in their potency to become different tissue types. Adult stem cells and cord blood stem cells have less capacity to become different tissues than pluripotent or embryonic stem cells.4 Embryonic stem cells can potentially generate any tissue in the body and carry a reduced risk for being rejected by the immune system.4,5 Although embryonic stem cells are derived from an embryo consisting of less than a couple hundred cells, there has been much ethical and religious controversy over whether such an embryo should be considered human.
In August 2001, President George W. Bush attempted to compromise by limiting federal research funding to a few dozen embryonic cell lines. In March 2009, President Barack Obama removed some of the restrictions. Nonetheless, a study published in 2011 indicated that nearly half of stem cell scientists surveyed reported that the political uncertainty had substantially affected their research or desire to continue working in the field.6
Science does not work like a light switch. Once research is mostly “turned off” (as occurred in 2001), it isn’t instantly “turned on” in response to changed government policy.
World Stem Cell Summit
The World Stem Cell Summit 2012, held December 3-5, 2012, in West Palm Beach, Florida, was organized to not simply be a scientific conference, but to be a conference on all issues related to stem cells. Many of those in attendance were patients in wheelchairs who were eager for research and available therapies. When there were parallel sessions (as there often are), I opted to attend the scientific sessions rather than the ones dealing with law, ethics, industry, or patient advocacy. With so much hype about the potentials of stem cell therapy, my prime interest at the World Stem Cell Summit was to learn what medicine has actually accomplished with stem cells. Nonetheless, there were plenary (general) sessions on all topics which I attended along with most of the others attending the conference.
Decades of Stem Cell Therapy
Stem cells have been used in medicine for decades, primarily for the treatment of certain cancers and blood disorders,7,8 but those have been adult stem cells rather than the embryonic stem cells that have caused so much controversy. More recently, umbilical cord blood stem cells have been used because the immature immune system in cord blood results in fewer immune incompatibilities,9 and because stem cells from cord blood have greater potency than adult stem cells.10 As noted above, ethical, political, and legal controversies3,6 have greatly reduced the development and application of embryonic stem cell therapies. Shinya Yamanaka won a 2012 Nobel Prize for his 2006 discovery that four proteins could stimulate four genes to convert connective tissue cells into pluripotent stem cells.11,12 Whether these induced pluripotent stem cells are equivalent in potency and safety to embryonic stem cells is an unresolved scientific question.13
Stem Cell Clinical Trials
Chris Mason, PhD, (Professor of Regenerative Medicine Bioprocessing, University College London, London, England) moderated a panel at which he discussed current clinical trials of stem cell treatments. Thousands of clinical trials are currently in progress for stem cell therapies, but at least half of them are only in Phase I.14
Artificial Organs from Stem Cells
Paolo Macchiarini, MD, PhD, (Professor of Regen-erative Medicine, Karolinska Institute, Stockholm, Sweden) was a keynote speaker who reported on his breakthroughs in transplantation using stem cells. In 2008, he achieved the world’s first successful tissue-engineered bronchial transplant.15 He started with the trachea of a donor which would serve as a biological scaffold for the stem cells, he colonized the trachea with epithelial and stem cell-derived chondrocytes (cells found in cartilage) cultured from cells taken from the recipient (a 30-year-old woman), and successfully transplanted the bronchus into the recipient. He performed a similar tracheal transplant into a 36-year-old cancer victim in 2011.16 Dr. Macchiarini spoke of the difficulties of getting the stem cells to integrate into the biological scaffold, not just colonize on the surface of the scaffold.
Joshua Hunsberger, PhD, (Research Fellow, NIH Center for Regenerative Medicine, Bethesda, Maryland) was also a keynote speaker. He talked about what the National Institutes of Health (NIH) has done to advance the field of regenerative medicine. Similar to the work Dr. Macchiarini reported with tracheas, Dr. Hunsberger spoke about clinical trials of bladder replacement using artificial bladder scaffolds seeded with stem cells from patients.17,18 He described the use of gene therapy on induced pluripotent stem cells from a patient suffering a rare genetic immune cell disease.19 Inherited defective genes were modified in the pluripotent stem cells from the patient, and after the corrective modification were reintroduced into the patient. (A similar combination of gene therapy and stem cell therapy may have cured an individual of HIV infection.)20 The NIH is also attempting to confer stemness to immune system cells to make those cells more effective at combating cancer.21
Stem Cells for Heart Disease
Carl Pepine, MD, (Professor, Division of Cardio-vascular Medicine, University of Florida, Gainesville, Florida) noted that for years, heart attack victims have been receiving into their hearts infusions of adult stem cells taken from their bone marrow. Those patients have shown improved heart function, reduced incidence of death, and reduced incidence of subsequent heart attack.22-24 Dr. Pepine has been developing a hydrogel for improved delivery of stem cells to heart tissue.25
Leslie Miller, MD, (Director, Heart Institute, University of South Florida, Tampa, Florida) questioned the use of bone marrow stem cells for heart treatment, especially for patients over age 60. Stem cells from fat tissue are at least a hundred times more plentiful than stem cells from bone marrow and are easily extracted by liposuction.26 Preclinical trials in Denmark indicate that fat-derived stem cells can promote new blood vessels and differentiate into cardiomyocytes to replace injured heart muscle.27 Dr. Miller said that stem cells from fat tissue would soon be available in Europe, but not in the USA because of the FDA.
Joseph Wu, MD, PhD, (Associate Professor, Cardiovascular Medicine & Radiology, Stanford University, Palo Alto, California) is also interested in treatment of cardiovascular disease with stem cells. But rather than use adult stem cells from bone marrow or fat, he wants to use induced pluripotent stem cells (iPSCs). He has successfully derived iPSCs from dogs and pigs28,29 and he has successfully transplanted porcine-derived iPSCs into mouse hearts to achieve improved heart function.29
Stem Cells for Nervous Tissue
Wado Akamatsu, MD, PhD, (Assistant Professor, School of Medicine, Keio University, Tokyo, Japan) reported on the use of iPSCs from humans that were used to treat spinal cord injury in mice.30 Dr. Akamatsu was also able to directly induce the formation of neural stem cells from mouse connective tissue cells without an intermediate step of iPSCs.31
Karen Abooty, MD, (Associate Professor of Neurosciences, City of Hope, Duarte, California) is an activist in the effort to accelerate the process of translating research results into clinical therapies (“from bench to bedside”).32 In her presentation she spoke of her efforts to use neural stem cells to treat brain cancer in rodents.33 Neural stem cells can cross the blood-brain barrier, migrate toward tumors in the brain, and are a non-toxic alternative to chemotherapy and radiation therapy.
Ovarian Stem Cells
Jonathan Tilly, PhD, (Director, Vincent Center for Reproductive Biology, Harvard Stem Cell Institute, Boston, Massachusetts) has been studying mouse ovaries for nearly a decade. It was long believed that female mammals are born with a fixed number of oocytes (egg cells) in their ovaries, but in 2004 Tilly demonstrated that mice have ovarian stem cells that can generate new oocytes.34 He later showed that sustaining ovarian function into advanced age prevented mouse menopause leading to a significant reduction in age-related health problems, but no increase in cancer.35
Most recently Tilly has found strong evidence for oocyte stem cells in women, but legal, ethical, and technical limitations prevented the same comprehensive validation as was done for mice.36 Tilly wants to convince doubters by attempting to fertilize the oocytes in the UK, which he is not permitted to do in the US with federal funding.37 Tilly is hopeful that delayed menopause by oocyte stem cell preservation can produce similar benefits for women as he achieved with mice.
Medical Tourism for Stem Cell Therapy
James Guest, MD, PhD, (Associate Professor of Neurological Surgery, University of Miami, Miami, Florida) did not speak of his research, but instead warned against the dangers of stem cell medical tourism, both to patients and to the field of stem cell medicine. The field of gene therapy had been paralyzed by the death of a single gene therapy patient.38 Many foreign stem cell clinics are exaggerating therapeutic benefits and down-playing the risks.
Dr. Guest said there is a widespread perception that the US government is blocking access to stem cell therapies for Americans, and this perception is driving desperate patients abroad into the hands of charlatans. He hastened to acknowledge, however, that many medical innovations are occurring outside the US that could not occur within the US.39 He said that the role of physicians should be to influence or warn against dangers, rather than to stop their patients from seeking stem cell therapies abroad.
Stem Cell Therapy and the FDA
My concentration on attending scientific sessions caused me to miss many sessions dealing with patient advocacy and regulatory issues, but in the general sessions I would have expected to see much more about the role of the FDA in blocking rapid translation of stem cell research into therapy. It is believed that the biotech giant Geron halted its massive clinical trial program to use stem cells for treatment of spinal cord injuries partly because of the onerous requirements imposed by the FDA.40,41 One study described the FDA as a political organization that is more concerned with protecting its reputation than in protecting public health.42
If the stem cell advocacy groups are to be effective, in hastening application of new therapies they should be calling for the repeal of the 1962 Kefauver-Harris Amendment that added a proof-of-efficacy requirement to the proof-of-safety requirements for FDA drug approval. Requiring efficacy in addition to safety in the wake of the 1962 thalidomide scare was pure politics; thalidomide was entirely a safety issue.
The effect of the Kefauver-Harris Amendment was to reduce the availability of new drugs to the public. The average number of new drugs introduced dropped from 40 per year before 1962 to 16 per year soon after 1962.43 Average time from filing to approval for new drugs rose from 7 months before 1962 to 7.8 years by 1998.40 A 2006 study estimated the cost to bring a new drug to market at between $500 million to $2 billion.44
After FDA approval, safety rather than efficacy is mainly what matters because physicians are free to prescribe the drug “off label” for any indication they please. And FDA-approved drugs are not very safe, anyway. The American Medical Association has reported that adverse reactions to FDA-approved drugs in American hospitals is a leading cause of death.45
For those who want to see greatly accelerated availability of safe stem cell therapies, the Kefauver-Harris Amendment should be repealed.
Stem cell therapy has the potential to transform medicine from mostly just treating symptoms to restoration of healthy, youthful tissue following every injury, disease, and age-associated degeneration. Unfortunately, the federal ban placed on stem cell research in 2001 has markedly delayed the introduction of this breakthrough therapy into clinical practice application. Stem cells vary in their potency to become different tissue types. Adult stem cells and cord blood stem cells have less capacity to become different tissues than pluripotent or embryonic stem cells.4 Embryonic stem cells can potentially generate any tissue in the body and carry a reduced risk for being rejected by the immune system.4,5 Stem cells have been used in medicine for decades, primarily for the treatment of certain cancers and blood disorders.7,8 Currently, thousands of clinical trials are underway to evaluate the use of stem cell therapies for a variety of anti-aging and clinical applications.
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- Karanes C, Nelson GO, Chitphakdithai P, et al. Twenty years of unrelated donor hematopoietic cell transplantation for adult recipients facilitated by the National Marrow Donor Program. Biol Blood Marrow Transplant. 2008 Sep;14(9 Suppl):8-15.
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- Macchiarini P, Jungebluth P, Go T,et al. Clinical transplantation of a tissue-engineered airway. Lancet. 2008 Dec 13;372(9655): 2023-30.
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