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从三种组织来源分离的间充质基质细胞(MSCs)的分泌组研究揭示了效力上的细微差异。

Secretome studies of mesenchymal stromal cells (MSCs) isolated from three tissue sources reveal subtle differences in potency.

机构信息

Department of Marine-Biotechnology, AMET University, Kanathur, Chennai, 600040, India.

Genes & Life Health Care Pvt. Ltd., Punjagutta, Hyderabad, 500082, India.

出版信息

In Vitro Cell Dev Biol Anim. 2020 Oct;56(9):689-700. doi: 10.1007/s11626-020-00501-1. Epub 2020 Oct 2.

Abstract

Human mesenchymal stromal cells (MSCs) are currently the leading candidate for cell-based therapeutics. While the use of MSCs in transplantation therapies is widely expanding, still, there is a lot of scope for better understanding of the mechanisms underlying their effects. We have generated MSCs from pre- and post-natal human tissue sources such as Wharton's jelly (WJ), stem cells from human exfoliated deciduous teeth (SHED), and bone marrow (BM). We then expanded, banked, and characterized them based on morphology, growth kinetics, senescence, immunophenotype, gene expression, and secretion of growth factors. Although the immunophenotype was very similar across MSCs from the three types of donor tissues, they showed minor variations in their growth kinetics. Further, a higher percentage of senescent cells were observed in BM-MSCs than in WJ-MSCs and SHED. Gene expression analysis showed the increased expression of INF-γ, PDGFA, VEGF, IL10, and SDF in SHED over WJ-MSC and BM-MSC. Comparative secretome profiling by ELISA demonstrated the presence of FGF-2, IL-10, PDGF, SDF-1, Ang-1, TGF-β3, HGF, INF-γ, VEGF, and IL-6 in cell culture supernatants. Based on our findings, WJ-MSC and SHED appear more potent than BM-MSC for managing inflammation, immunomodulation, angiogenesis, fibrosis, and scarring. Due to widespread application of MSCs in cell replacement therapy, these subtle differences need to be taken into consideration while designing stem cell-based clinical trials.

摘要

人骨髓间充质干细胞(MSCs)目前是细胞治疗的主要候选者。尽管 MSCs 在移植治疗中的应用正在广泛扩展,但仍有很多机会更好地了解其作用的机制。我们已经从产前和产后的人组织来源(如 Wharton 胶)、人脱落乳牙(SHED)和骨髓(BM)中生成了 MSCs。然后,我们根据形态、生长动力学、衰老、免疫表型、基因表达和生长因子分泌对它们进行了扩增、储存和特征分析。尽管三种供体组织来源的 MSCs 的免疫表型非常相似,但它们的生长动力学存在细微差异。此外,BM-MSCs 中的衰老细胞比例高于 WJ-MSCs 和 SHED。基因表达分析显示,SHED 中 INF-γ、PDGFA、VEGF、IL10 和 SDF 的表达增加,而 WJ-MSC 和 BM-MSC 则减少。通过 ELISA 进行的比较分泌组分析表明,细胞培养上清液中存在 FGF-2、IL-10、PDGF、SDF-1、Ang-1、TGF-β3、HGF、INF-γ、VEGF 和 IL-6。根据我们的发现,WJ-MSC 和 SHED 似乎比 BM-MSC 更能有效地治疗炎症、免疫调节、血管生成、纤维化和瘢痕形成。由于 MSCs 在细胞替代治疗中的广泛应用,在设计基于干细胞的临床试验时,需要考虑这些细微差异。

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