【原】SMAD信号通路抑制剂：Noggin & SB-431542

 Inducible pluripotent stem cells for the treatment of ischemic stroke: Current status and problems

诱导多能干细胞治疗缺血性脑卒中：研究现状及问题

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|核心内容：

摘要：尽管在医疗和外科护理方面取得了巨大的进步，但对缺血性中风的有效临床治疗方法有限。干细胞移植已成为缺血性脑损伤细胞替代的一种潜在的治疗方法。诱导多能干细胞(iPSCs)已成为移植的替代细胞来源。它们具有有效的神经分化能力，而没有伦理和免疫排斥的问题。诱导多能干细胞在缺血性脑损伤的临床前模型中已被观察到重要的功能。然而，关于使用诱导多能干细胞治疗缺血性中风仍存在几个问题：致瘤性、诱导多能干细胞衍生方法差和未定义的传递变量。随着诱导多能干细胞研究的发展，缺血性脑卒中的高效、无瘤细胞治疗将达到更安全、更有效的策略。

Figure   1  Mechanisms for increased differentiation of neural cells by inhibition of the SMAD pathway.    (A) Noggin can bind bone morphogenetic protein (BMP)-2,4,7 with high affinity to prevent their ligation with BMP-2, BMP-4, and BMP-7  receptors. (B) Dorsomorphin can selectively inhibit the BMP type I receptors (ALK2, ALK3, ALK6) and further blocks BMP-mediated SMAD- 1,5,8 phosphorylation. (C) SB-431542 can selectively inhibit transforming growth factor-beta (TGF β ) type I receptor (ALK-5), activin type I  receptor (ALK-4) and nodal type I receptor (ALK-7) and thus blocks phosphorylation of SMAD-2 and SMAD-3 (Inman et al., 2002; Pera et al.,  2004; Chiba et al., 2008; Yu et al., 2008; Chambers et al., 2009; Wada et al., 2009; Morizane et al., 2011).

原文摘要：

 Abstract: Despite dramatic advancements in medical and  surgical care, effective clinical therapies for ischemic  stroke are limited. Stem-cell transplantation has emerged  as a potential therapeutic approach for cell replacement in  ischemic brain injuries. Inducible pluripotent stem cells  (iPSCs) have become an alternative cell source for transplantation. They possess efficient capacities for neural  differentiation without ethical and immune-rejection  concerns. Substantial function of iPSCs in pre-clinical  models of ischemic brain injury has been observed.  However, several problems remain regarding the treatment of ischemic stroke with iPSCs: tumorigenicity,  poor iPSC derivation methods, and undefined delivery  variables. With the development of iPSC research, safer  and more effective strategies will be achieved for highly  effective and tumor-free cell treatment of ischemic stroke.

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参考文献：https://www./publication/232610181_Inducible_pluripotent_stem_cells_for_the_treatment_of_ischemic_stroke_Current_status_and_problems

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