Ariyachet Chaiyaboot, Tovaglieri Alessio, Xiang Guanjue, Lu Jiaqi, Shah Manasvi S, Richmond Camilla A, Verbeke Catia, Melton Douglas A, Stanger Ben Z, Mooney David, Shivdasani Ramesh A, Mahony Shaun, Xia Qing, Breault David T, Zhou Qiao
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA.
Cell Stem Cell. 2016 Mar 3;18(3):410-21. doi: 10.1016/j.stem.2016.01.003. Epub 2016 Feb 18.
The gastrointestinal (GI) epithelium is a highly regenerative tissue with the potential to provide a renewable source of insulin(+) cells after undergoing cellular reprogramming. Here, we show that cells of the antral stomach have a previously unappreciated propensity for conversion into functional insulin-secreting cells. Native antral endocrine cells share a surprising degree of transcriptional similarity with pancreatic β cells, and expression of β cell reprogramming factors in vivo converts antral cells efficiently into insulin(+) cells with close molecular and functional similarity to β cells. Induced GI insulin(+) cells can suppress hyperglycemia in a diabetic mouse model for at least 6 months and regenerate rapidly after ablation. Reprogramming of antral stomach cells assembled into bioengineered mini-organs in vitro yielded transplantable units that also suppressed hyperglycemia in diabetic mice, highlighting the potential for development of engineered stomach tissues as a renewable source of functional β cells for glycemic control.
胃肠道（GI）上皮是一种高度再生的组织，在经历细胞重编程后，有潜力提供可再生的胰岛素阳性细胞来源。在此，我们表明胃窦细胞具有一种此前未被认识到的转化为功能性胰岛素分泌细胞的倾向。天然胃窦内分泌细胞与胰腺β细胞在转录上具有惊人程度的相似性，并且在体内β细胞重编程因子的表达能有效地将胃窦细胞转化为胰岛素阳性细胞，这些细胞在分子和功能上与β细胞非常相似。诱导产生的胃肠道胰岛素阳性细胞能够在糖尿病小鼠模型中至少6个月抑制高血糖，并且在消融后能迅速再生。体外将胃窦细胞组装成生物工程化微型器官进行重编程，产生了可移植单元，这些单元同样能抑制糖尿病小鼠的高血糖，这凸显了将工程化胃组织开发为用于血糖控制的功能性β细胞可再生来源的潜力。
