Characterization of neural crest-derived stem cells isolated from human bone marrow for improvement of transplanted islet function

  • Anja Brboric Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
  • Svitlana Vasylovska Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
  • Jonna Saarimäki-Vire Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, Faculty of Medicine, University of Helsinki, Helsinki, Finland
  • Daniel Espes Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden; Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  • José Caballero-Corbalan Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  • Gunnar Larfors Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  • Timo Otonkoski Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, Faculty of Medicine, University of Helsinki, Helsinki, Finland
  • Joey Lau Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
Keywords: Adult bone marrow, diabetes, islet transplantation, neural crest stem cells, pluripotent stem cells

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.

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Published
2019-10-18
How to Cite
Brboric, A., Vasylovska, S., Saarimäki-Vire, J., Espes, D., Caballero-Corbalan, J., Larfors, G., Otonkoski, T., & Lau, J. (2019). Characterization of neural crest-derived stem cells isolated from human bone marrow for improvement of transplanted islet function. Upsala Journal of Medical Sciences, 124(4), 228-237. https://doi.org/10.1080/03009734.2019.1658661
Section
Original Articles

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