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

Yasaman Aghazadeh; Frankie Poon; Farida Sarangi; Frances T M Wong; Safwat T Khan; Xuetao Sun; Rupal Hatkar; Brian J Cox; Sara S Nunes; M Cristina Nostro

doi:10.1016/j.stem.2021.08.001

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

Cell Stem Cell. 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diabetes Mellitus, Type 1* / therapy
Human Embryonic Stem Cells*
Humans
Islets of Langerhans Transplantation*
Islets of Langerhans*
Mice
Microvessels

Grants and funding

PJT153160/CIHR/Canada