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Human Cord Blood–Derived Cells Generate Insulin-Producing Cells In Vivo

^a Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medicine, Fukuoka, Japan;
^b First Department of Internal Medicine, Ehime University School of Medicine, Toon, Japan;
^c Morphology Core, Kyushu University, Fukuoka, Japan;
^d Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Ohmura, Japan;
^e The Jackson Laboratory, Bar Harbor, Maine, USA

Key Words. Human cord blood • Neonate • Insulin • Pancreas

Correspondence: Fumihiko Ishikawa, M.D., Ph.D., Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medicine, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Telephone: 81-92-642-5230; Fax: 81-92-642-5247; e-mail: f_ishika{at}intmed1.med.kyushu-u.ac.jp; and Leonard D. Shultz, Ph.D., The Jackson Laboratory, Bar Harbor, Maine 04609, USA. Telephone: 207-288-6405; Fax: 207-288-6079; e-mail: lenny.shultz{at}jax.org

Here we report the capacity of human cord blood (CB)–derived cells to generate insulin-producing cells. To investigate in vivo capacity of human CB–derived cells, T cell–depleted mononuclear cells were intravenously transplanted into nonobese diabetic/severe combined immunodeficient/ß₂-microglobulin^null mice within 48 hours of birth. At 1–2 months post-transplantation, immunofluorescence staining for insulin and fluorescence in situ hybridization (FISH) analysis using a human chromosome probe indicated that human CB–derived cells generated insulin-producing cells at a frequency of 0.65% ± 0.64% in xenogeneic hosts. Reverse transcription–polymerase chain reaction analysis confirmed the transcription of human insulin in the pancreatic tissue of the recipient mice. To clarify the mechanism underlying CB-derived insulin-producing cells, double FISH analysis using species-specific probes was performed. Almost equal proportions of human chromosome⁺ murine chromosome^– insulin⁺ cells and human chromosome⁺ murine chromosome⁺ insulin⁺ cells were present in recipient pancreatic islets. Taken together, human CB contains progenitor cells, which can generate insulin-producing cells in recipient pancreatic tissues across a xenogeneic histocompatibility barrier by fusion-dependent and -independent mechanisms.