Making the Switch: Alternatives to Fetal Bovine Serum for Adipose-Derived Stromal Cell Expansion.

Making the Switch: Alternatives to Fetal Bovine Serum for Adipose-Derived Stromal Cell Expansion.
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DOI:
10.3389/fcell.2016.00115
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发表时间:
2016
影响因子:
5.5
通讯作者:
Pepper MS
Pepper MS
中科院分区:
生物学2区
文献类型:
--
作者:
Dessels C;Potgieter M;Pepper MS

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脂肪来源的基质细胞(ASC)正在广泛用于临床试验。这些试验要求ASC使用良好生产规范(GMP)制备,并且可安全用于人类。大多数扩展ASC的临床试验都使用胎牛血清(FBS)。虽然FBS传统上用于体外扩增的研究环境中,但当用于扩增用于治疗目的的细胞时,它确实存在异种免疫和人畜共患病传播的风险。为了确保用于细胞治疗的GMP质量产品,已经使用无异种(XF)、化学定义的和人血来源的替代品进行ASC的体外扩增。这些研究通常包括国际细胞治疗学会(ISCT)和国际脂肪应用技术学会(IFATS)提出的标准。大多数研究使用这些标准来比较不同培养基补充条件下ASCs的塑料粘附、形态学、免疫表型和三系分化。基于这些研究,FBS的所有替代品似乎都是合适的替代品;然而,每种替代品都有自己的优点和缺点。很少有研究调查补充剂对ASC的免疫调节的影响;转录组,蛋白质组和分泌组;以及在适当的动物模型中的最终效果。培养基补充的选择将取决于ASC的下游应用及其在临床前研究中的功效和安全性。
Adipose-derived stromal cells (ASCs) are being used extensively in clinical trials. These trials require that ASCs are prepared using good manufacturing practices (GMPs) and are safe for use in humans. The majority of clinical trials in which ASCs are expanded make use of fetal bovine serum (FBS). While FBS is used traditionally in the research setting for in vitro expansion, it does carry the risk of xenoimmunization and zoonotic transmission when used for expanding cells destined for therapeutic purposes. In order to ensure a GMP quality product for cellular therapy, in vitro expansion of ASCs has been undertaken using xeno-free (XF), chemically-defined, and human blood-derived alternatives. These investigations usually include the criteria proposed by the International Society of Cellular Therapy (ISCT) and International Fat Applied Technology Society (IFATS). The majority of studies use these criteria to compare plastic-adherence, morphology, the immunophenotype and the trilineage differentiation of ASCs under the different medium supplemented conditions. Based on these studies, all of the alternatives to FBS seem to be suitable replacements; however, each has its own advantages and drawbacks. Very few studies have investigated the effects of the supplements on the immunomodulation of ASCs; the transcriptome, proteome and secretome; and the ultimate effects in appropriate animal models. The selection of medium supplementation will depend on the downstream application of the ASCs and their efficacy and safety in preclinical studies.
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