Division of Cardiovascular Diseases, Departments of Medicine and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Cell Transplant. 2011;20(6):797-811. doi: 10.3727/096368910X543376. Epub 2010 Nov 19.
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.
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。