Human platelet lysate can replace fetal bovine serum for clinical-scale expansion of functional mesenchymal stromal cells

Human platelet lysate can replace fetal bovine serum for clinical-scale expansion of functional mesenchymal stromal cells
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DOI:
10.1111/j.1537-2995.2007.01220.x
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发表时间:
2007-08-01
期刊:
影响因子:
2.9
通讯作者:
Strunk, Dirk
Strunk, Dirk
中科院分区:
医学3区
文献类型:
--
作者:
Schallmoser, Katharina;Bartmann, Christina;Strunk, Dirk

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背景技术背景:人多能间充质基质细胞(MSC)是越来越多的再生和免疫调节细胞疗法的有前途的候选人。由于MSC增殖依赖于胎牛血清(FBS),因此将良好的实验结果转化为临床应用受到了限制。研究设计和方法:分析了人血小板溶解物(HPL)替代FBS进行临床规模MSC增殖的能力。结果:HPL可以从血沉棕黄层中有效产生。多重分析允许一个独特的HPL生长因子的轮廓被描绘。通过先前建立的两步临床规模的程序,HPL在支持MSC生长方面比FBS可重复地更有效。仅用3 × 10(5)个原代培养物衍生的MSC,在单个第二次11- 13天培养步骤中获得平均4.36 × 10(8)个HPL-MSC(范围,3.01 × 10(8)-5.40 × 10(8))。虽然形态上不同,HPL-MSCs和FBS-MSCs没有显着不同的免疫表型,分化潜力在体外,并缺乏在裸鼠体内的致瘤性invivo.CONCLUSIONS:替换FBS与HPL防止牛朊病毒,病毒和动物源性污染的干细胞产品。这种用于临床规模MSC增殖的新的有效的无FBS两步法可能代表了挑战新干细胞疗法的重要一步。
BACKGROUND: Human multipotent mesenchymal stromal cells (MSCs) are promising candidates for a growing spectrum of regenerative and immunomodulatory cellular therapies. Translation of auspicious experimental results into clinical applications has been limited by the dependence of MSC propagation from fetal bovine serum (FBS).STUDY DESIGN AND METHODS: The capacity of human platelet lysate (HPL) to replace FBS for clinicalscale MSC propagation was analyzed.RESULTS: HPL could be efficiently produced from buffy coats. Multiplex analyses allowed a distinct HPL growth factor profile to be delineated. With a previously established two-step clinical-scale procedure, HPL was reproducibly more efficient than FBS in supporting MSC outgrowth. With only 3 x 10(5) primary culture-derived MSCs, a mean of 4.36 x 10(8) HPL-MSCs (range, 3.01 x 10(8)-5.40 x 10(8)) was obtained within a single secondary 11- to 13-day culture step. Although morphologically distinct, HPL-MSCs and FBS-MSCs did not differ significantly in terms of immunophenotype, differentiation potential in vitro, and lack of tumorigenicity in nude mice in vivo.CONCLUSIONS: Replacing FBS with HPL prevents bovine prion, viral, and zoonose contamination of the stem cell product. This new efficient FBS-free two-step procedure for clinical-scale MSC propagation may represent a major step toward challenging new stem cell therapies.