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血小板裂解液包含天然修复蛋白质组,支持人骨髓间充质干细胞的增殖和染色体稳定性。

Platelet lysate consisting of a natural repair proteome supports human mesenchymal stem cell proliferation and chromosomal stability.

机构信息

Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.

出版信息

Cell Transplant. 2011;20(6):797-811. doi: 10.3727/096368910X543376. Epub 2010 Nov 19.

Abstract

With favorable regenerative and immunotolerant profiles, patient-derived human mesenchymal stem cells (hMSCs) are increasingly considered in cell therapy. Derived from bone marrow (BM) and standardized with culture in fetal bovine serum (FBS), translation of hMSC-based approaches is impeded by protracted expansion times, risk of xenogenic response, and exposure to zoonoses. Here, human platelet lysate adherent to good manufacturing practices (GMP-hPL) provided a nonzoonotic adjuvant that enhanced the capacity of BM-hMSC to proliferate. The nurturing benefit of GMP-hPL was generalized to hMSC from adipose tissue evaluated as an alternative to bone marrow. Long-term culture in GMP-hPL maintained the multipotency of hMSC, while protecting against clonal chromosomal instability detected in the FBS milieu. Proteomic dissection identified TGF-β, VEGF, PDGF, FGF, and EGF as highly ranked effectors of hPL activity, revealing a paradigm of healing that underlies platelet lysate adjuvancy. Thus, GMP-adherent human platelet lysate accelerates hMSC proliferation with no chromosomal aberrancy, through an innate repair paradigm.

摘要

具有有利的再生和免疫耐受特性,患者来源的人骨髓间充质干细胞(hMSCs)在细胞治疗中越来越受到关注。来源于骨髓(BM),并在胎牛血清(FBS)中标准化培养,基于 hMSC 的方法的转化受到延长的扩增时间、异种反应风险和接触人畜共患病的阻碍。在这里,符合良好生产规范(GMP-hPL)的人血小板裂解物提供了一种非人畜共患病的佐剂,增强了 BM-hMSC 的增殖能力。GMP-hPL 的培育益处被推广到脂肪组织来源的 hMSC,作为骨髓的替代物进行评估。在 GMP-hPL 中长期培养维持了 hMSC 的多能性,同时防止了在 FBS 环境中检测到的克隆染色体不稳定性。蛋白质组学分析鉴定出 TGF-β、VEGF、PDGF、FGF 和 EGF 是 hPL 活性的高排名效应物,揭示了血小板裂解物佐剂所基于的愈合范例。因此,GMP 粘附的人血小板裂解物通过先天修复范例加速 hMSC 增殖,而不会导致染色体异常。

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