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      Differentiation of human umbilical cord blood-derived mononuclear cells to endocrine pancreatic lineage

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      Differentiation
      Elsevier BV

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          Abstract

          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 (immuno-competent) mice to check their ability to differentiate into insulin-producing cells. We observe that after 9 weeks of transplantation, approximately 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 in vivo. 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.

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          Author and article information

          Journal
          Differentiation
          Differentiation
          Elsevier BV
          03014681
          November 2009
          November 2009
          : 78
          : 4
          : 232-240
          Article
          10.1016/j.diff.2009.07.004
          19664871
          2e8e0508-be47-4541-988c-b2982b735db7
          © 2009

          https://www.elsevier.com/tdm/userlicense/1.0/

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