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成人人类间充质干细胞(Prochymal®)疗法的潜在临床应用。

Potential clinical applications of adult human mesenchymal stem cell (Prochymal®) therapy.

作者信息

Patel Amit N, Genovese Jorge

机构信息

University of Utah School of Medicine, Salt Lake City, UT, USA.

出版信息

Stem Cells Cloning. 2011 Nov 17;4:61-72. doi: 10.2147/SCCAA.S11991. eCollection 2011.

DOI:10.2147/SCCAA.S11991
PMID:24198531
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3781758/
Abstract

In vitro, in vivo animal, and human clinical data show a broad field of application for mesenchymal stem cells (MSCs). There is overwhelming evidence of the usefulness of MSCs in regenerative medicine, tissue engineering, and immune therapy. At present, there are a significant number of clinical trials exploring the use of MSCs for the treatment of various diseases, including myocardial infarction and stroke, in which oxygen suppression causes widespread cell death, and others with clear involvement of the immune system, such as graft-versus-host disease, Crohn's disease, and diabetes. With no less impact, MSCs have been used as cell therapy to treat defects in bone and cartilage and to help in wound healing, or in combination with biomaterials in tissue engineering development. Among the MSCs, allogeneic MSCs have been associated with a regenerative capacity due to their unique immune modulatory properties. Their immunosuppressive capability without evidence of immunosuppressive toxicity at a global level define their application in the treatment of diseases with a pathogenesis involving uncontrolled activity of the immune system. Until now, the limitation in the number of totally characterized autologous MSCs available represents a major obstacle to their use for adult stem cell therapy. The use of premanufactured allogeneic MSCs from controlled donors under optimal conditions and their application in highly standardized clinical trials would lead to a better understanding of their real applications and reduce the time to clinical translation.

摘要

体外、体内动物及人体临床数据表明,间充质干细胞(MSCs)具有广泛的应用领域。有压倒性的证据证明MSCs在再生医学、组织工程和免疫治疗中有用。目前,有大量临床试验在探索使用MSCs治疗各种疾病,包括心肌梗死和中风,在这些疾病中缺氧会导致广泛的细胞死亡,以及其他明显涉及免疫系统的疾病,如移植物抗宿主病、克罗恩病和糖尿病。同样具有重要影响的是,MSCs已被用作细胞疗法来治疗骨和软骨缺陷并促进伤口愈合,或在组织工程开发中与生物材料联合使用。在MSCs中,同种异体MSCs因其独特的免疫调节特性而与再生能力相关。它们的免疫抑制能力在整体水平上没有免疫抑制毒性的证据,这决定了它们在治疗发病机制涉及免疫系统不受控制活动的疾病中的应用。到目前为止,可用的完全表征的自体MSCs数量有限,这是其用于成人干细胞治疗的主要障碍。在最佳条件下使用来自受控供体的预制同种异体MSCs,并将其应用于高度标准化的临床试验,将有助于更好地了解它们的实际应用,并缩短临床转化时间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca1/3781758/d03d2382cb56/sccaa-4-061Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca1/3781758/d03d2382cb56/sccaa-4-061Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca1/3781758/d03d2382cb56/sccaa-4-061Fig1.jpg

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Human mesenchymal stem cells play a dual role on tumor cell growth in vitro and in vivo.人骨髓间充质干细胞在体外和体内对肿瘤细胞生长起双重作用。
J Cell Physiol. 2011 Jul;226(7):1860-7. doi: 10.1002/jcp.22511.
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Chromosomal variability of human mesenchymal stem cells cultured under hypoxic conditions.
Front Pharmacol. 2022 Oct 12;13:971541. doi: 10.3389/fphar.2022.971541. eCollection 2022.
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Standard toxicity study of clinical-grade allogeneic human bone marrow-derived clonal mesenchymal stromal cells.临床级同种异体人骨髓来源克隆间充质基质细胞的标准毒性研究。
Stem Cell Res Ther. 2022 May 26;13(1):213. doi: 10.1186/s13287-022-02899-9.
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Research-Based Product Innovation to Address Critical Unmet Needs of Patients with Inflammatory Bowel Diseases.基于研究的产品创新,以满足炎症性肠病患者的关键未满足需求。
Inflamm Bowel Dis. 2021 Nov 15;27(Suppl 2):S1-S16. doi: 10.1093/ibd/izab230.
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The tissue origin of human mesenchymal stem cells dictates their therapeutic efficacy on glucose and lipid metabolic disorders in type II diabetic mice.人骨髓间充质干细胞的组织来源决定了其在 II 型糖尿病小鼠糖脂代谢紊乱中的治疗效果。
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