Rationale for Determining the Functional Potency of Mesenchymal Stem Cells in Preventing Regulated Cell Death for Therapeutic Use.
Rationale for Determining the Functional Potency of Mesenchymal Stem Cells in Preventing Regulated Cell Death for Therapeutic Use.
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DOI：
10.5966/sctm.2016-0289
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发表时间：
2017-03
影响因子：
6
通讯作者：
Deschaseaux F
中科院分区：
文献类型：
--
作者：
Naji A;Suganuma N;Espagnolle N;Yagyu KI;Baba N;Sensebé L;Deschaseaux F
间充质干细胞（间质）细胞（MSC）正在研究用于治疗退行性和炎症性疾病，因为它们的修复和免疫调节特性。复杂的机制将细胞死亡过程与免疫反应联系起来，这对退行性和炎症性疾病有影响。我们综述了骨髓间充质干细胞在预防调节性细胞死亡（RCD）方面的治疗价值。当细胞识别损伤时，引起特定的细胞内途径用于执行RCD过程，例如凋亡、坏死性凋亡和焦亡。在某种程度上，恶化的RCD可以引起强烈的炎症反应，反之亦然。新兴的研究集中在MSC部署的分子机制，以改善不适合的免疫或非免疫细胞的生存，生物能量学和功能。鉴于这些方面，并在调节细胞死亡过程中的MSC的行动，我们建议使用新的功能性体外试验，以确保MSC预防RCD的效力。此类分析应与现有的体外测量MSC抗炎能力的功能测定相关联。基于两个体外功能标准（即，预防炎症和RCD）在体内具有最佳的治疗效果。此外，我们强调这些观点在MSC治疗的临床研究中的意义，特别关注急性呼吸窘迫综合征。干细胞转化医学2017;6：713-719
Mesenchymal stem (stromal) cells (MSCs) are being investigated for treating degenerative and inflammatory disorders because of their reparative and immunomodulatory properties. Intricate mechanisms relate cell death processes with immune responses, which have implications for degenerative and inflammatory conditions. We review the therapeutic value of MSCs in terms of preventing regulated cell death (RCD). When cells identify an insult, specific intracellular pathways are elicited for execution of RCD processes, such as apoptosis, necroptosis, and pyroptosis. To some extent, exacerbated RCD can provoke an intense inflammatory response and vice versa. Emerging studies are focusing on the molecular mechanisms deployed by MSCs to ameliorate the survival, bioenergetics, and functions of unfit immune or nonimmune cells. Given these aspects, and in light of MSC actions in modulating cell death processes, we suggest the use of novel functional in vitro assays to ensure the potency of MSCs for preventing RCD. Such analyses should be associated with existing functional assays measuring the anti‐inflammatory capabilities of MSCs in vitro. MSCs selected on the basis of two in vitro functional criteria (i.e., prevention of inflammation and RCD) could possess optimal therapeutic efficacy in vivo. In addition, we underline the implications of these perspectives in clinical studies of MSC therapy, with particular focus on acute respiratory distress syndrome. Stem Cells Translational Medicine 2017;6:713–719