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TISSUE-SPECIFIC STEM CELLS

Formation of Pancreatic Duct Epithelium from Bone Marrow During Neonatal Development

^a Division of Research Immunology/Bone Marrow Transplantation,
^b Department of Pathology,
^c Congressman Julian Dixon Cellular Imaging Core,
^d Division of Gastroenterology, Hepatology, and Nutrition, and
^e Developmental Biology Program, Childrens Hospital Los Angeles, Los Angeles, California, USA

Key Words. Bone marrow transplantation • Epithelial stem cells • Pancreas • Ducts • Neonate • Mice

Correspondence: Gay M. Crooks, M.D., Division of Research Immunology/BMT, Childrens Hospital Los Angeles, 4650 Sunset Blvd., M.S. #62, Los Angeles, CA 90027, USA. Telephone: 323-669-5690; Fax: 323-906-8193; e-mail: gcrooks{at}chla.usc.edu

Recent reports suggest that bone marrow–derived cells engraft and differentiate into pancreatic tissue at very low frequency after pancreatic injury. All such studies have used adult recipients. The aim of our studies was to investigate the potential of bone marrow to contribute to the exocrine and endocrine components of the pancreas during the normal rapid growth of the organ that occurs during the neonatal period. Five to ten million bone marrow cells from adult, male, transgenic, green fluorescent protein (GFP) mice were injected into neonatal nonobese diabetic/severely compromised immunodeficient/ß2microglobulin-null mice 24 hours after birth. Two months after bone marrow transplantation, pancreas tissue was analyzed with fluorescence immunohistochemistry and fluorescence in situ hybridization (FISH). Co-staining of GFP, with anticytokeratin antibody, and with FISH for the presence of donor Y chromosome indicated that up to 40% of ducts (median 4.6%) contained epithelial cells derived from donor bone marrow. In some of these donor-derived ducts, there were clusters of large and small ducts, all comprised of GFP⁺ epithelium, suggesting that whole branching structures were derived from donor bone marrow. In addition, rare cells that coexpressed GFP and insulin were found within islets. Unlike pancreatic damage models, no bone marrow–derived vascular endothelial cells were found. In contrast to the neonatal recipients, bone marrow transplanted into adult mice rarely generated ductal epithelium or islet cells (p < .05 difference between adult and neonate transplants). These findings demonstrate the existence in bone marrow of pluripotent stem cells or epithelial precursors that can migrate to the pancreas and differentiate into complex organ-specific structures during the neonatal period.

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