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人诱导多能干细胞衍生的诱导间充质干细胞:作为再生医学中一种先进的具有治疗活性的细胞资源的新一代间充质干细胞。

hiPSC-derived iMSCs: NextGen MSCs as an advanced therapeutically active cell resource for regenerative medicine.

作者信息

Sabapathy Vikram, Kumar Sanjay

机构信息

Center for Stem Cell Research, A Unit of inStem Bengaluru, Christian Medical College, Vellore, Tamil Nadu, India.

出版信息

J Cell Mol Med. 2016 Aug;20(8):1571-88. doi: 10.1111/jcmm.12839. Epub 2016 Apr 21.

Abstract

Mesenchymal stem cells (MSCs) are being assessed for ameliorating the severity of graft-versus-host disease, autoimmune conditions, musculoskeletal injuries and cardiovascular diseases. While most of these clinical therapeutic applications require substantial cell quantities, the number of MSCs that can be obtained initially from a single donor remains limited. The utility of MSCs derived from human-induced pluripotent stem cells (hiPSCs) has been shown in recent pre-clinical studies. Since adult MSCs have limited capability regarding proliferation, the quantum of bioactive factor secretion and immunomodulation ability may be constrained. Hence, the alternate source of MSCs is being considered to replace the commonly used adult tissue-derived MSCs. The MSCs have been obtained from various adult and foetal tissues. The hiPSC-derived MSCs (iMSCs) are transpiring as an attractive source of MSCs because during reprogramming process, cells undergo rejuvination, exhibiting better cellular vitality such as survival, proliferation and differentiations potentials. The autologous iMSCs could be considered as an inexhaustible source of MSCs that could be used to meet the unmet clinical needs. Human-induced PSC-derived MSCs are reported to be superior when compared to the adult MSCs regarding cell proliferation, immunomodulation, cytokines profiles, microenvironment modulating exosomes and bioactive paracrine factors secretion. Strategies such as derivation and propagation of iMSCs in chemically defined culture conditions and use of footprint-free safer reprogramming strategies have contributed towards the development of clinically relevant cell types. In this review, the role of iPSC-derived mesenchymal stromal cells (iMSCs) as an alternate source of therapeutically active MSCs has been described. Additionally, we also describe the role of iMSCs in regenerative medical applications, the necessary strategies, and the regulatory policies that have to be enforced to render iMSC's effectiveness in translational medicine.

摘要

间充质干细胞(MSCs)正在被评估用于减轻移植物抗宿主病、自身免疫性疾病、肌肉骨骼损伤和心血管疾病的严重程度。虽然这些临床治疗应用大多需要大量细胞,但最初从单个供体获得的MSCs数量仍然有限。来自人诱导多能干细胞(hiPSCs)的MSCs的效用已在最近的临床前研究中得到证实。由于成体MSCs在增殖、生物活性因子分泌量和免疫调节能力方面的能力有限,因此正在考虑使用MSCs的替代来源来取代常用的成人组织来源的MSCs。MSCs已从各种成人和胎儿组织中获得。hiPSC来源的MSCs(iMSCs)正成为一种有吸引力的MSCs来源,因为在重编程过程中,细胞会经历年轻化,表现出更好的细胞活力,如存活、增殖和分化潜力。自体iMSCs可被视为一种取之不尽的MSCs来源,可用于满足未满足的临床需求。据报道,与成体MSCs相比,人诱导PSC来源的MSCs在细胞增殖、免疫调节、细胞因子谱、调节外泌体的微环境和生物活性旁分泌因子分泌方面更具优势。在化学成分确定的培养条件下衍生和扩增iMSCs以及使用无足迹更安全的重编程策略等方法,有助于开发临床相关的细胞类型。在这篇综述中,描述了iPSC来源的间充质基质细胞(iMSCs)作为治疗活性MSCs替代来源的作用。此外,我们还描述了iMSCs在再生医学应用中的作用、必要的策略以及为使iMSCs在转化医学中发挥作用而必须实施的监管政策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb2b/4956943/3f1a085a9b29/JCMM-20-1571-g001.jpg

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