Studies of Stem Cells

Stem cells derived from adult tissues are endowed with the unique capacity to regenerate functional organs. Multipotent stem cells not only undergo self-renewal but also differentiate under permissive conditions into lineage-specific progenitors that could potentially revitalize every organ. Adult organs-including bone marrow, myocardium, vascular system, liver, and lung-harbor renewal sources of endogenous stem cells that could contribute to the regeneration of damaged tissue. Adult bone marrow is also a rich reservoir of hematopoietic and vascular stem and progenitor cells.

As the stem cell reservoir in the adult organs is scant, it may be difficult, using current technology, to obtain sufficient numbers of transplantable stem cells that could be used clinically. Alternatively, embryonic and fetal stem cells, as well as reprogrammable germline stem cells, are a rich source of stem cells that can be used for therapeutic organ regeneration and revascularization. Furthermore, because stem cells can support tumor growth and metastasis, understanding how tumor tissue recruits tumor stem cells and vascular progenitors will make it possible to design new strategies to block tumor growth and inhibit tumor neo-angiogenesis.

Despite the tremendous potential for the use of adult or embryonic stem cells for organ regeneration or to target tumor tissue, the molecular and cellular pathways that support recruitment and differentiation of stem cells into functional organs remain unknown. Furthermore, recent setbacks with stem cell therapy for myocardial regeneration suggest that breakthroughs are necessary to take advantage of stem cells and their progeny for organ regeneration and repair.

Significant hurdles must be overcome, however, to facilitate the introduction of stem cells into the clinic for organ regeneration and revascularization: Adult stem cells are scarce and thus their use for generation of large tissues is not practical. Adult stem cells are primarily programmed to generate a very specific set of tissues, and thus have limited multipotentiality. Culture conditions that will promote differentiation of stem cells into functional tissues must be identified.

Rafii's lab has developed a number of strategies to circumvent these obstacles.