The term stem cell refers to the pluripotential nature of the cell. These amazing cells have the ability to transform into one of the 220 different phenotypic cell types found in humans. They also possess great regenerative power and can multiply infinitely in addition to their phenotypic capabilities. Three stem cell types exist: embryonic, adult, and induced pluripotent stem (iPS) cells.
Embryonic stem cells are pluripotent—having the ability to become any phenotypic cell type in the body. Once cells begin to divide, they differentiate several times into one particular phenotype by expressing genes specific to this cell type. Most cells in our body can be described as adult cells and have a specific phenotype. However, some cells maintain their ability to multiply and change phenotypes. Termed adult stem cells, these special cells exist within small regions of certain tissues that require regenerative capabilities to respond to damage or excessive use. Adult stem cells have been isolated from skin, bone, fat, muscle, intestine, vascular, and brain tissues.1-3 Unlike the pluripotential abilities of embryonic stem cells, adult stem cells are multipotential and can be changed into several different phenotypes but cannot differentiate into all 220 phenotypes that exist in nature. Initially, researchers believed that bone marrow aspirates were a good source of mesenchymal stem cells, but their harvest required the use of a trocar to obtain a bone specimen and further steps to isolate the small number of stem cells present.4-6
Using an in vitro model, I was able to demonstrate the presence of multipotential stem cells in the periosteum, the tissue that covers the surface of the bone.7 The cambium, or inner layer of the periosteum, contains mesenchymal stem cells. Clinically, we use this periosteum to cover articular cartilage defects during the CARTICEL autologous chondrocyte implantation procedure (Genzyme, Cambridge, MA).8 The inner layer of the periosteum is placed toward the articular cartilage defect on the surface of the knee joint. However, our in vitro study revealed a gradual senescence of the stem cells with periosteal age.7 As a result, we currently use a young patient's own perisoteum because the multipotential stem cells present within the periosteum may contribute to successful outcomes. In middle-aged and older individuals, senescence leads to a more limited contribution by the individual's periosteum in healing the defect. As a result, a replacement graft (cadaveric or xenographic) is recommended for these individuals to avoid excessive surgical time and increased incision size.
Recently, through genetic induction, cells have been pushed backward through their development, creating a pluripotential state.3,9-11 These induced cells from numerous sources are in a pliable condition and can be used to regenerate tissues and potentially treat clinical disease processes. In 1962, Dr Gurdon at the University of Cambridge produced living tadpoles by transferring the adult nucleus from an intestinal cell into a frog egg from which the nucleus had been removed.12-15 In 1997, his technique was repeated in a sheep model, producing the cloned sheep named Dolly and broadening public awareness surrounding genetic modification and its future applications.16-19 In 2007, Dr Yamanaka demonstrated the ability to add 4 key transcription factors to adult cells through viral transmission, creating the iPS cells.20,21 Drs Gurdon and Yamanaka won the 2012 Nobel Prize in Physiology or Medicine for their contributions to stem cell research.22
Dr Huard and his associates at the University of Pittsburgh Stem Cell Research Center have used muscle-derived cells to change the phenotypic character of these cells.3 Numerous basic science studies have demonstrated the potential clinical use of these cells to treat a variety of conditions, including ligament injuries, acute and chronic articular cartilage injuries, bone defects, meniscus tears, macular degeneration, spinal cord injuries, and chronic neural conditions such as Duchenne muscular dystrophy, Alzheimer disease, and Parkinson syndrome.5,11,23-27
The public debate surrounding stem cells heightened during the George W. Bush administration.28 When public access to this technology was limited in the United States during the second Bush presidency, other countries seized the opportunity and began developing their own research techniques and clinical treatments, opening the door for stem cell tourism.28 With increasing public awareness regarding stem cells and increased use in the clinical setting, the opportunity for misuse increased.
The typical patient inquiring about stem cell therapy has a chronic, debilitating, and incurable condition. These vulnerable individuals will pay large sums for unproven treatments. Einsiedel and Adamson examined 23 stem cell tourism websites; among them, only one website contained a brief mention of one clinical study.28 Despite the unproven nature of these therapies, clinicians providing them charge prices as high as $39,500. Several investigative articles surrounding the use of adult stem cells recently appeared in Nature29-31 and other journals.32,33 A Houston, Texas, company named Celltex Therapeutics Corp. currently pays physicians a fee for administering stem cells to patients and charges patients for the treatment of numerous conditions through intravenous infusion techniques. At the same time, Celltex conducts research on these treatments. The Nature articles raised the question of whether the research should be performed to determine efficacy prior to implementation of standard use of these treatments. Apparently, Celltex executives are aware of the ethical issues raised by these activities. The company recently hired the current editor-in-chief of the American Journal of Bioethics, Glenn McGee, as president for ethics and strategic initiatives.31 This move raised further questions about conflict of interest, and some in academics have asked McGee to step down from his editorial position.
Certainly, some individuals with chronic degenerative conditions such as multiple sclerosis will desire and have begun to use stem cells to treat their conditions prior to proven efficacy. Placebo-controlled, blinded clinical trials may be able to answer the question of clinical efficacy, but some patients will not wait because their conditions are progressive. Once again, technology has advanced more rapidly than our ethical considerations, and some patients may suffer harm as a result.
Case reports of complications in patients treated with stem cells are beginning to trickle in to the literature.34,35 Israeli doctors recently reported the development of a brain tumor in a young boy who had received fetal neural stem cells in Russia. This individual had a rare degenerative neural condition, and the Israeli doctors linked the tumor to cells introduced during stem cell therapy.34 A medical report from China implicated stem cell therapy in several cases of meningitis following treatment for spinal cord injuries.35
As is the case in all fields of medicine, physicians serve as a safety net for desperate individuals seeking stem cell treatment, weighing the risks of treatment with stem cells against the expected outcomes. Similarly, clinicians must understand and communicate the benefits of stem cell therapy to patients while remaining honest about the potential complications. In the end, the physician must follow the Hippocratic Oath: “Do no harm.”
- © Academic Division of Ochsner Clinic Foundation
