Hao E et al. (2006) Beta-cell differentiation from nonendocrine epithelial cells of the adult human pancreas. Nat Med 12: 310–316

Therapies for diabetes that aim to correct the endocrine deficit rely on transplanted pancreatic islets to replenish the insulin-producing β cells. Unfortunately, this strategy is limited by a shortage of suitable tissue and loss of function of transplanted islets over time. An alternative approach might be to stimulate production of the patient's own β cells, possibly by differentiation of endogenous stem cells or progenitor cells. Although such cells have been described in the fetal pancreas, the existence of adult pancreatic stem cells or progenitor cells is contested.

Hao et al. describe a novel method to enrich heterogeneous cultures of adult human nonendocrine pancreatic cells for cytokeratin-19-positive, duct-epithelial cells, representing a putative endocrine stem cell or progenitor cell population. When mixed with isolated fetal human pancreatic tissue—a rich source of endocrine precursor cells and inductive factors that promote β-cell differentiation from these precursors—and transplanted beneath the kidney capsules of immunodeficient mice, the purified nonendocrine pancreatic epithelial cells (NEPECs) differentiated into insulin-expressing, cytokeratin-19-negative cells. These differentiated NEPECs also expressed other β-cell markers, including C-peptide, glucokinase, NKX6.1, and PDX1. Importantly, the authors established that differentiation was not a consequence of fusion with fetal cells or replication of contaminating residual β cells.

Although many questions remain unanswered, including the nature of the inductive signal provided by the fetal cells, this study clearly demonstrates the endocrine potential of NEPECs and, therefore, the existence of endocrine stem cells or progenitor cells in the adult human. The authors speculate that NEPECs might support future regenerative treatments for diabetes.