Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University, Chongqing, People's Republic of China.
Center for Joint Surgery, Southwest Hospital, Army Medical University, Chongqing, People's Republic of China.
Stem Cell Res Ther. 2023 Nov 19;14(1):334. doi: 10.1186/s13287-023-03532-z.
Mesenchymal stem cells (MSCs) are adult stem cells with self-renewal and multi-directional differentiation potential and possess the functions of immunomodulation, regulation of cell growth, and repair of damage. Over recent years, MSCs have been found to regulate the secretion of inflammatory factors and to exert regulatory effects on various lymphocytes in inflammatory states, and on the subsequent repair of tissue damage caused by inflammation. In the present study, we analyzed the effects of tissue inflammation on the characteristics of MSCs.
Human fat derived from the infrapatellar fat pad (IPFP) of knees with differing degrees of inflammation was extracted from specimens derived from total knee arthroplasties. HE and immunohistochemical staining was performed to directly observe the evidence and degree of inflammation in human infrapatellar fat pad tissue in order to classify MSCs cells, by their origin, into highly inflamed and lowly inflamed groups, and to study the effect of tissue inflammation on cell acquisition rates via cellular counting data. Flow cytometry assays were performed to investigate the effect of tissue inflammation on MSC surface marker expression. Trilineage differentiation, including osteogenesis, adipogenesis, and chondrogenesis, was performed to assess the effect of tissue inflammation on the ability of MSCs to undergo directed differentiation. The effect of tissue inflammation on the ability of MSCs to proliferate was investigated via clone formation studies. RNA-sequencing was performed to evaluate the transcriptomes of MSCs derived from different areas of inflammation. The effect of tissue inflammation on tissue repair capacity and safety of MSCs was investigated via a murine model of acute liver injury.
The results of cell count data indicate that a high degree of tissue inflammation significantly decreases the acquisition rate of MSCs, and the proportion of CD34 and CD146 cells. The results of our trilineage differentiation assay show that a higher degree of inflammation decreases osteogenic differentiation and enhances adipogenic and chondrogenic differentiation of MSCs. However, these differences were not statistically significant. Clone formation assays indicate that the degree of tissue inflammation at the MSC source does not significantly affect the proliferative capacity of MSCs. The transcriptomes of MSCs remain relatively stable in fat pad tissues derived from both highly and lowly inflamed samples. The results of acute liver injury investigations in mice indicate that MSCs of high and low inflammatory tissue origin have no significant difference in their tissue repair capability.
High tissue inflammation at the source of MSCs reduces the acquisition rate of MSCs and the percentage of CD34 and CD146 cells acquisition. However, source tissue inflammation may not significantly affect trilineage differentiation potential and proliferative capacity of MSCs. Also, MSCs obtained from differing source degrees of inflammation retain stable and similar transcriptomic profile and are both safe and efficacious for tissue repair/regeneration without detectable differences.
间充质干细胞（MSCs）是具有自我更新和多向分化潜能的成体干细胞，具有免疫调节、细胞生长调节和损伤修复功能。近年来，人们发现 MSCs 可调节炎症因子的分泌，并对炎症状态下的各种淋巴细胞发挥调节作用，随后对炎症引起的组织损伤进行修复。本研究分析了组织炎症对 MSCs 特征的影响。
从全膝关节置换术获得的膝关节髌下脂肪垫（IPFP）中提取出不同程度炎症的人脂肪。通过 HE 和免疫组织化学染色直接观察人髌下脂肪垫组织中的炎症证据和程度，根据来源将 MSC 细胞分类为高度炎症和低度炎症组，并通过细胞计数数据研究组织炎症对细胞获取率的影响。通过流式细胞术检测组织炎症对 MSC 表面标志物表达的影响。进行三系分化，包括成骨、成脂和成软骨，以评估组织炎症对 MSC 定向分化能力的影响。通过克隆形成研究评估组织炎症对 MSC 增殖能力的影响。通过 RNA 测序评估来自不同炎症区域的 MSC 的转录组。通过急性肝损伤小鼠模型研究组织炎症对 MSC 组织修复能力和安全性的影响。
细胞计数数据结果表明，高度组织炎症显著降低 MSC 的获取率和 CD34 和 CD146 细胞的比例。三系分化试验结果表明，较高程度的炎症降低了 MSC 的成骨分化能力，并增强了 MSC 的成脂和成软骨分化能力。然而，这些差异没有统计学意义。克隆形成试验表明，MSC 来源组织的炎症程度对 MSC 的增殖能力没有显著影响。来自高度和低度炎症样本的脂肪垫组织中的 MSC 转录组相对稳定。急性肝损伤研究结果表明，来自高和低度炎症组织的 MSC 在组织修复能力方面没有显著差异。
MSC 来源组织的高度炎症会降低 MSC 的获取率和 CD34 和 CD146 细胞的获取比例。然而，组织炎症来源可能不会显著影响 MSC 的三系分化潜能和增殖能力。此外，从不同来源炎症程度获得的 MSC 保持稳定且相似的转录组谱，并且在组织修复/再生方面都是安全有效的，没有可检测到的差异。
