Abstract

Background: Murine boundary cap-derived neural crest stem cells (NCSCs) are capable of enhancing islet function by stimulating beta cell proliferation as well as increasing the neural and vascular density in the islets both in vitro and in vivo. This study aimed to isolate NCSC-like cells from human bone marrow.Methods: CD271 magnetic cell separation and culture techniques were used to purify a NCSC-enriched population of human bone marrow. Analyses of the CD271+ and CD271- fractions in terms of protein expression were performed, and the capacity of the CD271+ bone marrow cells to form 3-dimensional spheres when grown under non-adherent conditions was also investigated. Moreover, the NCSC characteristics of the CD271+ cells were evaluated by their ability to migrate toward human islets as well as human islet-like cell clusters (ICC) derived from pluripotent stem cells.Results: The CD271+ bone marrow population fulfilled the criterion of being multipotent stem cells, having the potential to differentiate into glial cells, neurons as well as myofibroblasts in vitro. They had the capacity to form 3-dimensional spheres as well as an ability to migrate toward human islets, further supporting their NCSC identity. Additionally, we demonstrated similar migration features toward stem cell-derived ICC.Conclusion: The results support the NCSC identity of the CD271-enriched human bone marrow population. It remains to investigate whether the human bone marrow-derived NCSCs have the ability to improve transplantation efficacy of not only human islets but stem cell-derived ICC as well.

Highlights

  • Clinical islet transplantation is an alternative treatment for a subgroup of type 1 diabetes patients suffering from severe hypoglycemic attacks and can temporarily cure the disease

  • We have previously shown that neural crest stem cells (NCSCs) from murine boundary cap have positive effects on islets after co-culture and transplantation

  • We investigated the potential of using magnetic cell separation with CD271 microbeads to label adult bone marrow NCSCs with high purity, suggesting that a positive selection would result in a more NCSC-like population of human bone marrow stromal cells

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Summary

Introduction

Clinical islet transplantation is an alternative treatment for a subgroup of type 1 diabetes patients suffering from severe hypoglycemic attacks and can temporarily cure the disease. Murine boundary cap-derived neural crest stem cells (NCSCs) are capable of enhancing islet function by stimulating beta cell proliferation as well as increasing the neural and vascular density in the islets both in vitro and in vivo. Results: The CD271þ bone marrow population fulfilled the criterion of being multipotent stem cells, having the potential to differentiate into glial cells, neurons as well as myofibroblasts in vitro They had the capacity to form 3-dimensional spheres as well as an ability to migrate toward human islets, further supporting their NCSC identity. Conclusion: The results support the NCSC identity of the CD271-enriched human bone marrow population It remains to investigate whether the human bone marrow-derived NCSCs have the ability to improve transplantation efficacy of human islets but stem cell-derived ICC as well

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