Aghazadeh Yasaman, Poon Frankie, Sarangi Farida, Wong Frances T M, Khan Safwat T, Sun Xuetao, Hatkar Rupal, Cox Brian J, Nunes Sara S, Nostro M Cristina
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.
McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Deparment of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Cell Stem Cell. 2021 Nov 4;28(11):1936-1949.e8. doi: 10.1016/j.stem.2021.08.001. Epub 2021 Sep 3.
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.
胰岛移植是1型糖尿病(T1D)一种很有前景的治疗方法,但供体库有限、胰岛植入不佳以及终身免疫抑制阻碍了它成为标准治疗方案。人胚胎干细胞(hESC)来源的胰腺细胞可以消除供体短缺问题,但仍需要采取干预措施来提高移植存活率。在此,我们采用了一种独特的血管化策略,即利用从脂肪组织中分离出的现成微血管(MVs),增强皮下植入效果。这使得人胰岛和hESC来源的胰腺细胞的细胞存活率提高,葡萄糖反应有效,改善了三种T1D小鼠模型中已有的糖尿病症状。