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From Mesenchymal Stromal/Stem Cells to Insulin-Producing Cells: Progress and Challenges.
Stem Cell Reviews and Reports ( IF 4.5 ) Pub Date : 2020-09-03 , DOI: 10.1007/s12015-020-10036-3
Mohamed A Ghoneim 1 , Ayman F Refaie 1 , Batoul L Elbassiouny 1 , Mahmoud M Gabr 1 , Mahmoud M Zakaria 1
Affiliation  

Mesenchymal stromal cells (MSCs) are an attractive option for cell therapy for type 1 diabetes mellitus (DM). These cells can be obtained from many sources, but bone marrow and adipose tissue are the most studied. MSCs have distinct advantages since they are nonteratogenic, nonimmunogenic and have immunomodulatory functions. Insulin-producing cells (IPCs) can be generated from MSCs by gene transfection, gene editing or directed differentiation. For directed differentiation, MSCs are usually cultured in a glucose-rich medium with various growth and activation factors. The resulting IPCs can control chemically-induced diabetes in immune-deficient mice. These findings are comparable to those obtained from pluripotent cells. PD-L1 and PD-L2 expression by MSCs is upregulated under inflammatory conditions. Immunomodulation occurs due to the interaction between these ligands and PD-1 receptors on T lymphocytes. If this function is maintained after differentiation, life-long immunosuppression or encapsulation could be avoided. In the clinical setting, two sites can be used for transplantation of IPCs: the subcutaneous tissue and the omentum. A 2-stage procedure is required for the former and a laparoscopic procedure for the latter. For either site, cells should be transplanted within a scaffold, preferably one from fibrin. Several questions remain unanswered. Will the transplanted cells be affected by the antibodies involved in the pathogenesis of type 1 DM? What is the functional longevity of these cells following their transplantation? These issues have to be addressed before clinical translation is attempted.



中文翻译:


从间充质基质/干细胞到胰岛素产生细胞:进展与挑战。



间充质基质细胞 (MSC) 是 1 型糖尿病 (DM) 细胞治疗的一个有吸引力的选择。这些细胞可以从许多来源获得,但骨髓和脂肪组织是研究最多的。间充质干细胞具有独特的优势,因为它们不致畸、无免疫原性并且具有免疫调节功能。胰岛素生成细胞 (IPC) 可以通过基因转染、基因编辑或定向分化从 MSC 中产生。为了定向分化,MSC 通常在含有各种生长和激活因子的富含葡萄糖的培养基中培养。由此产生的 IPC 可以控制免疫缺陷小鼠中化学诱导的糖尿病。这些发现与从多能细胞获得的结果相当。 MSC 的 PD-L 1和 PD-L 2表达在炎症条件下上调。免疫调节是由于这些配体与 T 淋巴细胞上的 PD-1 受体之间的相互作用而发生的。如果分化后维持这种功能,则可以避免终生免疫抑制或封装。在临床环境中,有两个部位可用于IPC的移植:皮下组织和大网膜。前者需要进行两阶段手术,后者需要进行腹腔镜手术。对于任一部位,细胞都应移植到支架内,最好是来自纤维蛋白的支架。有几个问题仍未得到解答。移植的细胞会受到参与 1 型糖尿病发病机制的抗体的影响吗?这些细胞移植后的功能寿命是多少?在尝试临床转化之前必须解决这些问题。

更新日期:2020-09-03
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