Journal
DIFFERENTIATION
Volume 78, Issue 4, Pages 232-240Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.diff.2009.07.004
Keywords
Human umbilical cord blood; Transplantation; Differentiation; Insulin; Diabetes
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Funding
- National Center for Cell Science [BT/PR7975/MED/14/1211/2006]
- Department of Biotechnology (DBT), Government of India
- Council of Scientific and Industrial Research (CSIR), Government of India
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Generation of insulin-producing cells remains a major limitation for cellular replacement therapy in treatment of diabetes. To understand the potential of human umbilical cord blood (hUCB)-derived mononuclear cells (MNCs) in cell replacement therapy for diabetes, we studied MNCs isolated from 270 human umbilical cord blood samples. We characterized these by immunostaining and real-time PCR and studied their ability to differentiate into insulin-producing cells. We observe that freshly isolated MNCs as well as mesenchymal-like cells grown out by in vitro culture of isolated MNCs express key pancreatic transcription factors: pdx1, ngn3, isl1, brn4 and pax6. However, after 32- fold expansion, MNCs show decreased abundance of pdx1 and ngn3, indicating that islet/pancreatic progenitors detected in freshly isolated MNCs die or are diluted out during in vitro expansion. We therefore transplanted freshly isolated MNCs in NOD/SCID (immuno-incompetent) or FVB/NJ (immunocompetent) mice to check their ability to differentiate into insulin-producing cells. We observe that after 9 weeks of transplantation, similar to 25% grafts exhibit human insulin-producing (16% immunopositive) cells. The number and abundance of pro-insulin transcript-containing cells increased when the animals underwent partial pancreatectomy, 15 days after transplantation. Our results indicate that such hUCB-derived MNC population contains a subset of pancreas-committed cells that have the potential to differentiate into insulin-producing cells invivo. Further studies in understanding the differentiation potential of this subset of pancreas-committed hUCB-derived MNCs will provide us with an autologous source of lineage-committed'' progenitors for cell replacement therapy in diabetes. (C) 2009 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.
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