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

被引:69
作者
Aghazadeh, Yasaman [1 ,2 ]
Poon, Frankie [1 ,3 ]
Sarangi, Farida [1 ]
Wong, Frances T. M. [3 ]
Khan, Safwat T. [2 ,4 ]
Sun, Xuetao [2 ]
Hatkar, Rupal [2 ]
Cox, Brian J. [3 ,5 ]
Nunes, Sara S. [2 ,4 ,6 ,7 ]
Nostro, M. Cristina [1 ,3 ]
机构
[1] Univ Hlth Network, McEwen Stem Cell Inst, Toronto, ON M5G 1L7, Canada
[2] Univ Hlth Network, Toronto Gen Hosp Res Inst, Toronto, ON M5G IL7, Canada
[3] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
[4] Univ Toronto, Inst Biomed Engn, Toronto, ON M5S 3G9, Canada
[5] Univ Toronto, Dept Obstet & Gynecol, Toronto, ON M5G 1E2, Canada
[6] Univ Toronto, Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada
[7] Univ Toronto, Heart & Stroke Richard Lewar Ctr Excellence, Toronto, ON M5S 3H2, Canada
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
GROWTH-FACTOR; TRANSCRIPTION FACTOR; ENDOTHELIAL-CELLS; BETA-CELLS; IN-VITRO; STEM; VASCULARIZATION; FRAGMENTS; TISSUE; DIFFERENTIATION;
D O I
10.1016/j.stem.2021.08.001
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:1936 / +
页数:23
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