Participation of Adult Bone Marrow-Derived Stem Cells in Pancreatic Regeneration: Neogenesis Versus Endogenesis

Regenerative medicine opens new avenues and promises towards more effective therapies for autoimmune disorders. Current therapeutic strategies for type I diabetes focus on three major directions, with distinct advantages and disadvantages: arrest of autoimmunity, islet transplantation and generation of neoislets. There is mounting evidence that candidate stem cells residing in the hematopoietic compartments participate in regeneration of pancreatic islets following chemical and autoimmune injury in vivo. The apparent major mechanisms include immunomodulation, revascularization, support of endogenous β-cell regeneration and differentiation into insulin-producing cells. Review of the current evidence suggests that some divergent observations depend primarily on the experimental design, which both limits and accentuates developmental events. The flood of publications reporting negative results appears to reflect primarily suboptimal experimental conditions for differentiation of putative stem cells, rather than limited developmental plasticity. Stem cells modulate the course of autoimmune diabetes through multiple mechanisms, including de novo generation of units capable to sense, produce and secrete insulin. Therefore, the charged debate over controversies surrounding developmental plasticity should not impede attempts to design curative therapies for this disease.