Stem Cell Biology Department, ICMR-National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai, 400012, India.
Stem Cell Res Ther. 2020 Jun 3;11(1):211. doi: 10.1186/s13287-020-01718-3.
Human embryonic stem (hES) cells have been around for more than two decades now. It was expected that hES/iPS (induced pluripotent stem) cells will quickly translate to the clinics to treat diabetic patients and to obtain gametes in vitro for infertile couples. However, there is no breakthrough yet in either of the fields although considerable progress has been made. Research efforts are ongoing to obtain an insight into the gene expression changes associated with directed differentiation of hES/iPS cells. Autologous bone marrow/cord blood mononuclear cells' therapy has also failed to show any regenerative potential and only remains as a standard method of care for blood diseases. Only mesenchymal stem cells (MSCs) have shown promise in the clinics to alleviate diabetic symptoms. But MSCs are stromal cells with no regenerative properties; rather "paracrine providers", pericytes/stromal cells, better known for their trophic, immuno-modulatory, and anti-inflammatory properties and thus best termed as mesenchymal stromal cells (MSCs). Autologus bone marrow cells enriched for hematopoietic stem cells have no potential to cross boundaries and transdifferentiate into other lineages including endodermal pancreatic cells. Endogenous, pluripotent, very small embryonic-like stem cells (VSELs) emerge as the most likely endogenous stem cell candidates to regenerate adult diabetic pancreas. Transplanted MSCs provide a healthy paracrine support required for endogenous/ resident VSELs to differentiate into acinar cells and islets in a diabetic pancreas to enable restoration of homeostasis. Our recently published study shows that VSELs exist and can be enriched from intact mouse pancreas as well as from the islets and increase in numbers in diabetic pancreas. Providing "regenerative pressure" by subjecting diabetic mice to partial pancreatectomy stimulated the VSELs to undergo differentiation into various cell types in an attempt to restore homeostasis. Double-blinded, placebo controlled clinical trials need to be undertaken to evaluate the efficacy of transplanting MSCs in diabetic patients with conviction since now underlying fine play of endogenous VSELs and niche providing MSCs has emerged.
人类胚胎干细胞（hES）已经存在了二十多年。人们曾期望 hES/iPS（诱导多能干细胞）细胞能迅速转化为临床，用于治疗糖尿病患者，并在体外获得配子，以帮助不孕夫妇。然而，这两个领域都没有取得突破，尽管已经取得了相当大的进展。研究人员正在努力深入了解与 hES/iPS 细胞定向分化相关的基因表达变化。自体骨髓/脐血单个核细胞治疗也未能显示出任何再生潜力，仅作为血液疾病的标准治疗方法。只有间充质干细胞（MSCs）在临床上显示出缓解糖尿病症状的潜力。但是，MSCs 只是基质细胞，没有再生特性；而是“旁分泌提供者”，即周细胞/基质细胞，以其营养、免疫调节和抗炎特性而闻名，因此最好被称为间充质基质细胞（MSCs）。富含造血干细胞的自体骨髓细胞没有跨越边界并转分化为其他谱系的潜力，包括内胚层胰腺细胞。内源性、多能、非常小的胚胎样干细胞（VSELs）作为最有可能的内源性干细胞候选物，可用于再生成年糖尿病胰腺。移植的 MSCs 提供了健康的旁分泌支持，使内源性/驻留的 VSELs 能够在糖尿病胰腺中分化为腺泡细胞和胰岛，从而恢复内稳态。我们最近发表的研究表明，VSELs 存在并可从完整的小鼠胰腺以及胰岛中富集，并在糖尿病胰腺中数量增加。通过对糖尿病小鼠进行部分胰腺切除术来施加“再生压力”，刺激 VSELs 分化为各种细胞类型，试图恢复内稳态。需要进行双盲、安慰剂对照的临床试验，以评估在糖尿病患者中移植 MSCs 的疗效，因为现在内源性 VSELs 的细微作用和提供 MSC 的小生境已经显现出来。
