Serum-Free Medium Enhances the Therapeutic Effects of Umbilical Cord Mesenchymal Stromal Cells on a Murine Model for Acute Colitis
Serum-Free Medium Enhances the Therapeutic Effects of Umbilical Cord Mesenchymal Stromal Cells on a Murine Model for Acute Colitis
复制标题
无血清培养基增强脐带间充质基质细胞对急性结肠炎小鼠模型的治疗效果。
DOI：
10.3389/fbioe.2020.00586
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发表时间：
2020-06-26
影响因子：
5.7
通讯作者：
Ma, Zhijie
中科院分区：
文献类型：
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作者：
Wu, Xiaoyun;Wu, Daocheng;Ma, Zhijie
由于安全性问题和批次间的差异性，动物血清的使用可能最终阻止体外培养间充质基质细胞（MSC）在临床环境中的应用。越来越多的监管压力限制了动物血清的使用，鼓励无血清、无异种和化学成分确定的培养基（S&XFM-CD）在干细胞制备过程中取代含血清培养基（SCM）。我们先前开发了用于扩增脐带来源的MSC（UCMSC）的S&XFM-CD。不同的培养条件会影响MSCs的功能，进而影响治疗效果和作用机制。本研究比较了S&XFM-CD（UCMSCS&XFM-CD）和SCM（UCMSCSCM）中的UCMSCs对实验性结肠炎的治疗作用及其机制。UCMSC（S&XFM-CD）在体重、疾病活动指数和组织学结肠炎评分方面均优于UCMSC（SCM）。UCMSC（S&XFM-CD）或UCMSC（SCM）迁移到损伤结肠的炎症部位，但表现出低水平的募集和持久性。内源性巨噬细胞的全身消耗损害了UCMSC（SCM）和UCMSCS&XFM-CD的治疗效果。此外，UCMSC（S&XFM-CD）比UCMSCSCM更显著地促进肠巨噬细胞从M1表型极化为M2表型，从而在结肠组织中产生更高水平的IL-10和更低水平的TNF-α，而在UCMSCSCM处理组中产生更高水平的IL-4。与RAW264.7细胞共培养的UCMSC（S&XFM-CD）可促进TSG-6和IL-6的释放，而UCMSC（SCM）可增加PGE（2）水平。总之，我们证明了S&XFM-CD中的UCMSC在实验性急性结肠炎模型中表现出改善的治疗效果，细胞因子分泌改变。
The usage of animal serum may ultimately prevent the application ofex vivocultured mesenchymal stromal cells (MSCs) in a clinical setting due to safety concerns and batch-to-batch variability. Increasing regulatory pressure to limit use of animal serum has been issued and serum-free, xeno-free, and chemically defined media (S&XFM-CD) is encouraged to replace serum-containing media (SCM) in the stem cell preparation process. We previously developed a S&XFM-CD for the expansion of umbilical cord-derived MSCs (UCMSCs). Different culture conditions affect the function of MSCs, which may further affect the therapeutic efficiency and mechanisms of action. In this study, we compared the therapeutic effect and mechanism of UCMSCs in S&XFM-CD (UCMSCS&XFM-CD) in experimental colitis with those in SCM (UCMSCSCM). UCMSC(S&XFM-CD)exhibited better therapeutic effects than UCMSC(SCM)by body weight, disease activity index, and histological colitis score. UCMSC(S&XFM-CD)or UCMSC(SCM)migrated to the inflammation site of injured colon, but exhibited low levels of recruitment and persistence. Systemic depletion of endogenous macrophages impaired the therapeutic effects of UCMSC(SCM)and UCMSCS&XFM-CD. Furthermore, UCMSC(S&XFM-CD)more markedly promoted intestinal macrophage polarisation from M1 to M2 phenotype to produce higher levels of IL-10 and lower levels of TNF-alpha in colon tissue than UCMSCSCM, while a higher level of IL-4 was produced in UCMSCSCM-treated group. UCMSC(S&XFM-CD)cocultured with RAW264.7 cells in a transwell system promoted the release of TSG-6 and IL-6, whereas UCMSC(SCM)increased PGE(2)levels. Taken together, we demonstrated that UCMSCs in S&XFM-CD exhibited improved therapeutic effects with altered cytokine secretion in an experimental acute colitis model.