Microvessels support engraftment and functionality of human islets and hESC-derived pancreatic progenitors in diabetes models

Affiliations

¹ McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada.
² McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Deparment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
³ McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada.
⁴ Deparment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
⁵ Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
⁶ Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada.
⁷ Deparment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON M5G 1E2, Canada.
⁸ Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Laboratory of Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Heart & Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, ON M5S 3H2, Canada. Electronic address: sara.vasconcelos@utoronto.ca.
⁹ McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Deparment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: cnostro@uhnresearch.ca.

PMID: 34480863
DOI: 10.1016/j.stem.2021.08.001

Free article

Microvessels support engraftment and functionality of human islets and hESC-derived pancreatic progenitors in diabetes models

Yasaman Aghazadeh et al. Cell Stem Cell. 2021.

Free article

. 2021 Nov 4;28(11):1936-1949.e8.

doi: 10.1016/j.stem.2021.08.001. Epub 2021 Sep 3.

Authors

Affiliations

¹ McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada.
² McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Deparment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
³ McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada.
⁴ Deparment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
⁵ Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
⁶ Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada.
⁷ Deparment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON M5G 1E2, Canada.
⁸ Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Laboratory of Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Heart & Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, ON M5S 3H2, Canada. Electronic address: sara.vasconcelos@utoronto.ca.
⁹ McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Deparment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: cnostro@uhnresearch.ca.

PMID: 34480863
DOI: 10.1016/j.stem.2021.08.001

Abstract

Islet transplantation is a promising treatment for type 1 diabetes (T1D), yet the low donor pool, poor islet engraftment, and life-long immunosuppression prevent it from becoming the standard of care. Human embryonic stem cell (hESC)-derived pancreatic cells could eliminate donor shortages, but interventions to improve graft survival are needed. Here, we enhanced subcutaneous engraftment by employing a unique vascularization strategy based on ready-made microvessels (MVs) isolated from the adipose tissue. This resulted in improved cell survival and effective glucose response of both human islets and hESC-derived pancreatic cells, which ameliorated preexisting diabetes in three mouse models of T1D.

Keywords: beta cells; embryonic stem cells; endothelial cells; islet transplantation; microvessels; pancreatic progenitors; regenerative medicine; subcutaneous; type 1 diabetes; vascularization.

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Conflict of interest statement

Declaration of interests M.C.N. has a patent licensed to Sernova Inc. and is a scientific consultant for Sigilon Therapeutics.

Comment in

Microvessels enhance vascularization and function of transplanted insulin-producing cells.
Powers AC, Brissova M. Powers AC, et al. Cell Metab. 2021 Nov 2;33(11):2103-2105. doi: 10.1016/j.cmet.2021.10.013. Cell Metab. 2021. PMID: 34731653
Pancreatic islets in bed with microvasculature-companions for life.
Hoesli CA, Kieffer TJ. Hoesli CA, et al. Cell Rep Med. 2021 Nov 16;2(11):100454. doi: 10.1016/j.xcrm.2021.100454. eCollection 2021 Nov 16. Cell Rep Med. 2021. PMID: 34841297 Free PMC article.

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Microvessels support engraftment and functionality of human islets and hESC-derived pancreatic progenitors in diabetes models

Affiliations

Microvessels support engraftment and functionality of human islets and hESC-derived pancreatic progenitors in diabetes models

Authors

Affiliations

Abstract

Conflict of interest statement

Comment in

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Molecular Biology Databases