Cell Replacement Therapy for Type 1 Diabetes Patients: Potential Mechanisms Leading to Stem-Cell-Derived Pancreatic β-Cell Loss upon Transplant.
Cell Replacement Therapy for Type 1 Diabetes Patients: Potential Mechanisms Leading to Stem-Cell-Derived Pancreatic β-Cell Loss upon Transplant.
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作者：
使用干细胞衍生的产生胰岛素的β样细胞（sBC）的细胞替代疗法已被提议作为1型糖尿病（T1 D）患者的实际治疗。sBC可以在临床前动物模型中纠正糖尿病，证明了这种基于干细胞的方法的前景。然而，体内研究已经证明，与尸体人胰岛类似，大多数sBC在移植时由于缺血和其他未知机制而丢失。因此，在当前领域中关于sBC在移植后的命运存在关键的知识缺口。在这里，我们审查，讨论的影响，并提出其他潜在的机制，可能有助于β细胞损失在体内。我们总结并强调了一些关于稳定、应激和患病糖尿病条件下β细胞表型丢失的文献。具体而言，我们专注于β细胞死亡，去分化为祖细胞，转分化为其他表达β细胞的细胞，和/或相互转化为功能较低的β细胞亚型作为潜在的机制。虽然目前采用sBC的细胞替代疗法作为丰富的细胞来源具有很大的前景，但解决体内β细胞损失的一些被忽视的方面将进一步加速sBC移植作为一种有前途的治疗方式，可以显着提高T1 D患者的生活质量。
Cell replacement therapy using stem-cell-derived insulin-producing β-like cells (sBCs) has been proposed as a practical cure for patients with type one diabetes (T1D). sBCs can correct diabetes in preclinical animal models, demonstrating the promise of this stem cell-based approach. However, in vivo studies have demonstrated that most sBCs, similarly to cadaveric human islets, are lost upon transplantation due to ischemia and other unknown mechanisms. Hence, there is a critical knowledge gap in the current field concerning the fate of sBCs upon engraftment. Here we review, discuss effects, and propose additional potential mechanisms that could contribute toward β-cell loss in vivo. We summarize and highlight some of the literature on phenotypic loss in β-cells under both steady, stressed, and diseased diabetic conditions. Specifically, we focus on β-cell death, dedifferentiation into progenitors, trans-differentiation into other hormone-expressing cells, and/or interconversion into less functional β-cell subtypes as potential mechanisms. While current cell replacement therapy efforts employing sBCs carry great promise as an abundant cell source, addressing the somewhat neglected aspect of β-cell loss in vivo will further accelerate sBC transplantation as a promising therapeutic modality that could significantly enhance the life quality of T1D patients.
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影响因子：
5.8
作者：
Carlsson, PO;Palm, F;Mattsson, G
通讯作者：
Mattsson, G
影响因子：
8.2
作者：
Carobbio, S;Ishihara, H;Maechler, P
通讯作者：
Maechler, P
影响因子：
46.9
作者：
Balboa, Diego;Barsby, Tom;Lithovius, Vaino;Saarimaki-Vire, Jonna;Omar-Hmeadi, Muhmmad;Dyachok, Oleg;Montaser, Hossam;Lund, Per-Eric;Yang, Mingyu;Ibrahim, Hazem;Naatanen, Anna;Chandra, Vikash;Vihinen, Helena;Jokitalo, Eija;Kvist, Jouni;Ustinov, Jarkko;Nieminen, Anni I.;Kuuluvainen, Emilia;Hietakangas, Ville;Katajisto, Pekka;Lau, Joey;Carlsson, Per-Ola;Barg, Sebastian;Tengholm, Anders;Otonkoski, Timo
通讯作者：
Otonkoski, Timo
影响因子：
3.7
作者：
do Amaral AS;Pawlick RL;Rodrigues E;Costal F;Pepper A;Galvão FH;Correa-Giannella ML;Shapiro AM
通讯作者：
Shapiro AM
影响因子：
3.3
作者：
Beattie, GM;Leibowitz, G;Hayek, A
通讯作者：
Hayek, A