Scientific Retreats 2009

April 6, 2009 (historical)

Stem Cell


Stem cells are characterized by both the ability to renew themselves, as well as to generate progeny that differentiate into more specialized cells. They play critical roles in the development of an organism. In adult tissues, somatic stem cells are essential for normal homeostasis and tissue repair.

The NIAMS has made a significant investment in stem cell research, as it pertains to NIAMS relevant tissues. Much of the NIAMS investment in stem cells has focused on the biology and application of adult stem cells, including bone marrow derived mesenchymal stem cells (MSC), stem cells and satellite cells obtained from skeletal muscle, and keratinocyte and other multipotent stem cells obtained from skin. A session at the 2006 NIAMS Scientific Retreat focused on the biology of stem cells in muscle and skin, with an emphasis on identification and characterization of the stem cell populations, regulation of stem cell maintenance within the stem cell niche, control of differentiation of stem cell progeny to more mature cell types, and the roles that the stem cells play in tissue homeostasis and the repair of tissue injury.

There have been rapid advances in the biology and understanding of stem cells in the last three years. There is currently considerable enthusiasm for the potential use of stem cells for tissue engineering and regenerative medicine. Stem cells for therapeutic use can be categorized as embryonic stem cells (ESC), adult (and fetal or neonatal)-derived stem cells (ASC), or induced pluripotent stem cells (iPSC). ASCs from bone marrow, skeletal muscle, and skin have the potential to regenerate tissues of interest to NIAMS. For example, keratinocyte stem cells can be expanded in culture and used to create human skin equivalents to treat burn patients. MSCs can be differentiated into multiple cell lineages that resemble osteoblasts, chondrocytes, myoblasts, adipocytes, and other cells. MSCs are often utilized for cell transplantation directly into tissues, or seeded in biomaterial scaffolds to repair tissues, such as bone or cartilage defects. Previous clinical trials of muscle progenitor cell transplantation for the treatment of muscular dystrophy were not successful, due to the poor survival of the transplanted cells. However, there have been significant advances in animal models using improved stem cell preparations, vascular delivery, and strategies to suppress the immune response or to induce tolerance to the transplanted cells. The accomplishments have sparked renewed interest in exploring cell therapy clinical trials for the dystrophies.

In theory, pluripotent embryonic stem cells (ESCs) might have scientific advantages for tissue engineering and regenerative medicine applications. For example, ESCs may prove less immunogenic or longer-lived than ASCs. Public policy has prevented the study of all hESCs except for a few approved cell lines (however, anticipated changes in regulations may allow broader use of hESCs in the near future). In 2006, Japanese researchers made the landmark discovery that pluripotent stem cells (now referred to as iPSCs) could be generated by the introduction of four transcription factors (Oct4, Sox2, Klf4, and c-Myc) into adult mouse skin fibroblasts; in 2007 these findings were extended to the generation of human iPSCs. However, the creation of iPSCs is still a very inefficient process, and considerable international effort is underway to find more efficient and safer ways to generate these cells. Patient-specific iPS cell lines have now been reported for several diseases, providing the tools for studies of disease pathogenesis, for screening of drugs, and for the combined gene and cell-based therapies for genetic defects. The NIAMS investment in human iPSCs is currently limited to a very small number of projects studying the reprogramming process, creating safer and more efficient ways to generate patient-specific iPSCs for gene and cell-based therapies, investigating disease pathogenesis and studying differentiation of stem cell progeny.

Goals of the Session

This session will discuss the current state of the science in stem cell research, including the biology of ESCs, iPSCs, and ASCs (with the emphasis on MSCs), their potential applications, as well as advantages and disadvantages, and opportunities for future NIAMS-funded research.