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Bone marrow–derived stem cells initiate pancreatic regeneration

Nature Biotechnology volume 21, pages 763–770 (2003)Cite this article

Abstract

We show that transplantation of adult bone marrow–derived cells expressing c-kit reduces hyperglycemia in mice with streptozotocin-induced pancreatic damage. Although quantitative analysis of the pancreas revealed a low frequency of donor insulin-positive cells, these cells were not present at the onset of blood glucose reduction. Instead, the majority of transplanted cells were localized to ductal and islet structures, and their presence was accompanied by a proliferation of recipient pancreatic cells that resulted in insulin production. The capacity of transplanted bone marrow–derived stem cells to initiate endogenous pancreatic tissue regeneration represents a previously unrecognized means by which these cells can contribute to the restoration of organ function.

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Figure 1: Pancreatic damage and induction of hyperglycemia after STZ treatment in NOD/SCID mice.
Figure 2: Reduction of elevated blood glucose in STZ-treated NOD/SCID mice after transplantation with functional whole bone marrow (BM) or purified c-kit-expressing BM cells.
Figure 3: Transplanted donor bone marrow (BM) cells engraft ductal and islet regions in recipient pancreas and produce a low frequency of donor insulin-positive (insulin+) cells devoid of PDX-1 expression.
Figure 4: Donor bone marrow–derived stem cells rapidly engraft the pancreas of recipient mice and induce endogenous pancreatic insulin production.
Figure 5: GFP+ donor cells in the pancreas of transplanted recipient mice promote the proliferation of cells in the ductal and pancreatic islet regions.
Figure 6: Pancreatic engraftment of donor-derived PECAM-1+ endothelial cells correlates with the rapid reduction of hyperglycemia after transplant.

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Acknowledgements

Funding for this research project was provided by the Canadian Institutes of Health Research, Asahi Kasei Corporation, and a fellowship award from the CIHR for D.H., and a Canadian Research Chair in Stem Cell Biology and Regenerative Medicine to M.B. Special thanks to Krysta Levac, Lisheng Wang, Francis Karanu, Julie McBride and Kristin Chadwick for their insights and assistance towards this work.

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  1. David Hess and Li Li: These authors contributed equally to this work.

Authors and Affiliations

  1. Robarts Research Institute, Stem Cell Biology and Regenerative Medicine, 100 Perth Drive, London, N6A 5K8, Ontario, Canada

    David Hess, Li Li, Matthew Martin & Mickie Bhatia

  2. The University of Western Ontario, 1151 Richmond Street, London, N6A 4B8, Ontario, Canada

    Matthew Martin, David Hill & Mickie Bhatia

  3. Asahi Kasei Corporation, Central R&D and Central Research Laboratory, 2-1 Samajima, Fuji, 416-8501, Shizuoka, Japan

    Seiji Sakano

  4. Lawson Health Research Institute, 268 Grosvenor Street, London, N6A 4V2, Ontario, Canada

    David Hill, Brenda Strutt & Sandra Thyssen

  5. Centre For Cancer Therapeutics, 503 Smyth Road, Ottawa, K1H 1C4, Ontario, Canada

    Douglas A Gray

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Correspondence to Mickie Bhatia.

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Hess, D., Li, L., Martin, M. et al. Bone marrow–derived stem cells initiate pancreatic regeneration. Nat Biotechnol 21, 763–770 (2003). https://doi.org/10.1038/nbt841

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