Accelerated Maturation of Human Stem Cell-Derived Pancreatic Progenitor Cells into Insulin-Secreting Cells in Immunodeficient Rats Relative to Mice.
Accelerated Maturation of Human Stem Cell-Derived Pancreatic Progenitor Cells into Insulin-Secreting Cells in Immunodeficient Rats Relative to Mice.
复制标题
DOI：
10.1016/j.stemcr.2015.10.013
复制
发表时间：
2015-12-08
影响因子：
5.9
通讯作者：
Kieffer TJ
中科院分区：
文献类型：
--
作者：
Bruin JE;Asadi A;Fox JK;Erener S;Rezania A;Kieffer TJ
多能性人类胚胎干细胞（hESC）是治疗糖尿病患者的可移植细胞的潜在来源。为了研究宿主受体对hESC衍生的胰腺祖细胞成熟的影响，将细胞移植到免疫缺陷的SCID-beige小鼠或裸大鼠中。移植后，小鼠的基础人类C肽水平始终高于大鼠，但只有大鼠在19-21周时显示出强劲的膳食和葡萄糖反应性人类C肽分泌。与小鼠相比，大鼠移植物含有较高比例的胰岛素：胰高血糖素免疫反应性，外分泌细胞较少，成熟β细胞标志物表达改善。此外，ECM相关基因丰富，胶原网络更密集，血管更复杂地整合到移植的内分泌组织中。总体而言，与SCID-米色小鼠相比，hESC衍生的胰腺祖细胞在裸大鼠中成熟得更快，表明宿主受体可以极大地影响移植后未成熟胰腺祖细胞的命运。人胚胎干细胞来源的胰腺祖细胞在裸鼠中比在SCID-bg小鼠中成熟得更快。在19周时，人C肽分泌在大鼠中受膳食调节，但在小鼠中不受膳食调节。与小鼠相比，来自大鼠的移植物表达更成熟的β细胞标志物。胰腺祖细胞的来源尚不清楚。在这篇文章中，Kieffer及其同事证明，与小鼠相比，免疫缺陷大鼠中hESC衍生的祖细胞更快地成熟为葡萄糖响应性胰岛素分泌细胞，这表明移植受体环境可以显著影响未成熟胰腺祖细胞的命运。
Pluripotent human embryonic stem cells (hESCs) are a potential source of transplantable cells for treating patients with diabetes. To investigate the impact of the host recipient on hESC-derived pancreatic progenitor cell maturation, cells were transplanted into immunodeficient SCID-beige mice or nude rats. Following the transplant, basal human C-peptide levels were consistently higher in mice compared with rats, but only rats showed robust meal- and glucose-responsive human C-peptide secretion by 19–21 weeks. Grafts from rats contained a higher proportion of insulin:glucagon immunoreactivity, fewer exocrine cells, and improved expression of mature β cell markers compared with mice. Moreover, ECM-related genes were enriched, the collagen network was denser, and blood vessels were more intricately integrated into the engrafted endocrine tissue in rats relative to mice. Overall, hESC-derived pancreatic progenitor cells matured faster in nude rats compared with SCID-beige mice, indicating that the host recipient can greatly influence the fate of immature pancreatic progenitor cells post-transplantation. hESC-derived pancreatic progenitor cells matured faster in nude rats than in SCID-bg mice Human C-peptide secretion was meal-regulated in rats but not in mice at 19 weeks Grafts from rats expressed more mature β cell markers compared with mice Grafts from rats had a denser ECM and greater vasculature than grafts from mice The potential influence of the in vivo environment on development of endocrine cells from hESC-derived pancreatic progenitor cells is unclear. In this article, Kieffer and colleagues demonstrate that hESC-derived progenitor cells mature significantly faster into glucose-responsive, insulin-secreting cells in immunodeficient rats compared with mice, indicating that the transplant recipient milieu can substantially affect the fate of immature pancreatic progenitor cells.