The State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Stem Cell Res Ther. 2019 Jan 11;10(1):19. doi: 10.1186/s13287-018-1104-x.
Mesenchymal stem cells (MSCs) have emerged as a promising regenerative tool, owing mainly to their multi-differentiation potential and immunosuppressive capacity. When compared with MSCs classically derived from the adult bone marrow (BM), MSCs of neonatal origins exhibit superior proliferation ability, lower immunogenicity, and possible lower incorporated mutation; hence, they are considered as an alternative source for clinical use. Several researches have focused on the biological differences among some neonatal MSCs cultured in serum-containing medium (SCM). However, since it has been reported that MSCs possess different biological characteristics when cultured in serum-free medium (SFM), these comparative studies in SCM cannot exactly represent the results under the serum-free Good Manufacturing Practice (GMP) standard.
Here, MSCs were isolated from three neonatal tissues, namely amniotic membrane (AM), umbilical cord (UC), and chorionic plate (CP), from the same donor, and their morphologies, immunophenotypes, trilineage differentiation potentials, global gene expression patterns, and proliferation abilities were systematically compared under chemical-defined SFM.
Our study demonstrated that these three neonatal MSCs exhibited a similar morphology and immunophenotypic pattern but various mesodermal differentiation potentials under SFM: amniotic membrane-derived MSCs showed a higher rate for osteogenic differentiation; chorionic plate-derived MSCs presented better adipogenic induction efficiency; and all these three neonatal MSCs exhibited similar chondrogenic potential. Moreover, by the analysis of global gene expression patterns, we speculated a possible higher proliferation ability of CP-MSCs in SFM, and we subsequently validated this conjecture.
Collectively, these results suggest that MSCs of different neonatal origins possess different biological features in SFM and thus may represent an optimal choice for different clinical applications.
间充质干细胞(MSCs)因其多向分化潜能和免疫抑制能力而成为一种有前途的再生工具。与经典的源自成人骨髓(BM)的 MSCs 相比,新生儿来源的 MSCs 表现出更强的增殖能力、更低的免疫原性和可能更低的整合突变率;因此,它们被认为是临床应用的替代来源。一些研究集中在含血清培养基(SCM)中培养的一些新生儿 MSCs 之间的生物学差异上。然而,由于已有报道称 MSCs 在无血清培养基(SFM)中具有不同的生物学特性,因此这些在 SCM 中的比较研究不能完全代表无血清良好生产规范(GMP)标准下的结果。
在这里,我们从同一位供体的三种新生儿组织(羊膜、脐带和胎盘)中分离出 MSCs,并在化学成分确定的 SFM 中系统比较它们的形态、免疫表型、三系分化潜能、全基因组表达模式和增殖能力。
我们的研究表明,这三种新生儿 MSCs 在 SFM 下表现出相似的形态和免疫表型模式,但具有不同的中胚层分化潜能:羊膜来源的 MSCs 具有更高的成骨分化率;胎盘来源的 MSCs 具有更好的成脂诱导效率;所有这三种新生儿 MSCs 均表现出相似的软骨形成潜力。此外,通过全基因组表达模式分析,我们推测 CP-MSCs 在 SFM 中可能具有更高的增殖能力,随后我们验证了这一推测。
综上所述,这些结果表明,不同来源的新生儿 MSCs 在 SFM 中具有不同的生物学特征,因此可能是不同临床应用的最佳选择。