Platelet Lysate Consisting of a Natural Repair Proteome Supports Human Mesenchymal Stem Cell Proliferation and Chromosomal Stability

被引:189
作者
Crespo-Diaz, Ruben [1 ,2 ]
Behfar, Atta [1 ,2 ]
Butler, Greg W. [3 ]
Padley, Douglas J. [3 ]
Sarr, Michael G. [4 ]
Bartunek, Jozef [5 ]
Dietz, Allan B. [3 ]
Terzic, Andre [1 ,2 ]
机构
[1] Mayo Clin, Marriott Heart Dis Res Program, Div Cardiovasc Dis, Dept Med, Rochester, MN 55905 USA
[2] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA
[3] Mayo Clin, Human Cellular Therapy Lab, Div Transfus Med, Dept Lab Med & Pathol, Rochester, MN USA
[4] Mayo Clin, Dept Gen Surg, Rochester, MN USA
[5] Cardiovasc Ctr, Aalst, Belgium
基金
美国国家卫生研究院;
关键词
Human mesenchymal stem cells (hMSCs); Human platelet lysate (hPL); Chromosomal stability; CLINICAL-GRADE PRODUCTION; FETAL CALF SERUM; BONE-MARROW; STROMAL CELLS; OCT4; EXPRESSION; GROWTH-FACTORS; CORD BLOOD; TGF-BETA; DIFFERENTIATION; EXPANSION;
D O I
10.3727/096368910X543376
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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-beta, 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.
引用
收藏
页码:797 / 811
页数:15
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