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利用心脏干细胞或重编程干细胞治疗心力衰竭。

Stemming heart failure with cardiac- or reprogrammed-stem cells.

作者信息

Tateishi Kento, Takehara Naofumi, Matsubara Hiroaki, Oh Hidemasa

机构信息

Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, and Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

出版信息

J Cell Mol Med. 2008 Dec;12(6A):2217-32. doi: 10.1111/j.1582-4934.2008.00487.x. Epub 2008 Aug 27.

Abstract

Despite extensive efforts to control myocyte growth by genetic targeting of the cell cycle machinery and small molecules for cardiac repair, adult myocytes themselves appeared to divide a limited number of times in response to a variety of cardiac muscle stresses. Rare tissue-resident stem cells are thought to exist in many adult organs that are capable of self-renewal and differentiation and possess a range of actions that are potentially therapeutic. Recent studies suggest that a population of cardiac stem cells (CSCs) is maintained after cardiac development in the adult heart in mammals including human beings; however, homeostatic cardiomyocyte replacement might be stem cell-dependent, and functional myocardial regeneration after cardiac muscle damage is not yet considered as sufficient to fully maintain or reconstitute the cardiovascular system and function. Although it is clear that adult CSCs have limitations in their capabilities to proliferate extensively and differentiate in response to injury in vivo for replenishing mature car-diomyocytes and potentially function as resident stem cells. Transplantation of CSCs expanded ex vivo seems to require an integrated strategy of cell growth-enhancing factor(s) and tissue engineering technologies to support the donor cell survival and subsequent proliferation and differentiation in the host microenvironment. There has been substantial interest regarding the evidence that mammalian fibroblasts can be genetically reprogrammed to induced pluripotent stem (iPS) cells, which closely resemble embryonic stem (ES) cell properties capable of differentiating into functional cardiomyocytes, and these cells may provide an alternative cell source for generating patient-specific CSCs for therapeutic applications.

摘要

尽管人们通过对细胞周期机制进行基因靶向调控以及利用小分子药物来控制心肌细胞生长以实现心脏修复付出了巨大努力,但成年心肌细胞在应对各种心肌应激时,自身似乎只能分裂有限次数。人们认为,许多成年器官中存在稀少的组织驻留干细胞,它们能够自我更新和分化,并具有一系列潜在的治疗作用。最近的研究表明,在包括人类在内的哺乳动物的成年心脏中,心脏发育后会保留一群心脏干细胞(CSCs);然而,稳态心肌细胞替代可能依赖于干细胞,并且心肌损伤后的功能性心肌再生尚未被认为足以完全维持或重建心血管系统及其功能。尽管很明显,成年CSCs在体内对损伤做出反应以补充成熟心肌细胞并潜在地作为驻留干细胞发挥作用时,其广泛增殖和分化的能力存在局限性。将体外扩增的CSCs进行移植似乎需要细胞生长增强因子和组织工程技术的综合策略,以支持供体细胞在宿主微环境中的存活以及随后的增殖和分化。关于哺乳动物成纤维细胞可以被基因重编程为诱导多能干细胞(iPS)细胞这一证据,已经引起了广泛关注,这些细胞与能够分化为功能性心肌细胞的胚胎干细胞(ES)细胞特性非常相似,并且这些细胞可能为生成用于治疗应用的患者特异性CSCs提供替代细胞来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e63/4514101/7dc934c237e5/jcmm0012-2217-f1.jpg

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