Phenotypic Determination and Characterization of Nestin-Positive Precursors Derived from Human Fetal Pancreas

Abstract

Demand for donations to meet the requirements of pancreas or islet transplantation has prompted the search for alternative sources of β-cell replacement therapy. Earlier studies identified nestin-positive islet-derived progenitor cells (NIPs) residing in human pancreas. In the present study, we isolated and cultured human fetal NIPs that express stem cell marker ABCG2/BCRP1. In confluent cultures, NIPs formed three-dimensional islet-like cell clusters (ICCs). During differentiation, NIP-derived ICCs showed numerous pancreatic lineage transcripts including insulin, whereas ABCG2 and nestin expression fell concomitantly. In addition, ICCs displayed the ability to reverse hyperglycemia in diabetic NOD-SCID mice, as well as infiltrate and form well-differentiated structures in normal mice. These cells can be cloned repeatedly and maintained in long-term culture. Our studies are the first to show NIPs derived from human fetal pancreas, which may have significant implications for future applications in stem cell therapy of diabetes.