Wang Meng, Yang Yuan, Yang Dongming, Luo Fei, Liang Wenjie, Guo Shuquan, Xu Jianzhong
Department of Orthopaedics, Southwest Hospital, Institute of Combined Injury of PLA, Third Millitary Medical University, Chongqing, China.
Immunology. 2009 Feb;126(2):220-32. doi: 10.1111/j.1365-2567.2008.02891.x. Epub 2008 Jun 24.
Bone marrow-derived mesenchymal stem cells (BM-MSC) are currently being investigated in preclinical and clinical settings because of their self-renewal and multipotent differentiative capacity or their immunosuppressive function. However, BM may be detrimental because of the highly invasive donation procedure and BM-MSC decline with age. Therefore, MSC derived from other sources have been considered as an alternative. However, there is only limited knowledge on their immunomodulatory properties. Human umbilical cord blood (UCB) cells are good substitutes for BM-MSC because of the immaturity of newborn cells. In this study, we successfully isolated MSC from UCB. The morphological phenotypes, cell cycle status, surface markers and differentiation potential of these clonally expanded cells are consistent with BM-MSC. Furthermore, UCB-MSC expanded in vitro retain low immunogenicity and an immunomodulatory effect. Flow cytometry analysis showed that UCB-MSC did not express CD40, CD40 ligand, CD80, CD86 and major histocompatibility complex class II molecules. We have demonstrated that UCB-MSC are incapable of inducing allogeneic peripheral blood mononuclear cell (PBMC) proliferation and have a dose-dependent inhibition of PBMC immune responses in mixed lymphocyte reactions (MLR) and phytohaemagglutinin activation assays, even after interferon-gamma treatment. Additionally, we have found that UCB-MSC can suppress the function of mature dendritic cells. Using transwell systems, we have demonstrated an inhibition mechanism that depends on both cell contact and soluble factors. Based on the findings we conclude that banked UCB could serve as a potential alternative source of MSC for allogeneic application in the future.
由于骨髓间充质干细胞（BM-MSC）具有自我更新和多能分化能力或免疫抑制功能，目前正在临床前和临床环境中进行研究。然而，由于骨髓捐赠过程具有高度侵入性，且BM-MSC会随着年龄增长而减少，因此骨髓可能具有不利影响。因此，来自其他来源的间充质干细胞已被视为一种替代方案。然而，关于它们的免疫调节特性的知识有限。由于新生儿细胞不成熟，人脐带血（UCB）细胞是BM-MSC的良好替代品。在本研究中，我们成功地从脐带血中分离出间充质干细胞。这些克隆扩增细胞的形态表型、细胞周期状态、表面标志物和分化潜能与BM-MSC一致。此外，体外扩增的脐带血间充质干细胞保留低免疫原性和免疫调节作用。流式细胞术分析表明，脐带血间充质干细胞不表达CD40、CD40配体、CD80、CD86和主要组织相容性复合体II类分子。我们已经证明，脐带血间充质干细胞不能诱导异体外周血单个核细胞（PBMC）增殖，并且在混合淋巴细胞反应（MLR）和植物血凝素激活试验中，即使在干扰素-γ处理后，对PBMC免疫反应也具有剂量依赖性抑制作用。此外，我们发现脐带血间充质干细胞可以抑制成熟树突状细胞的功能。使用Transwell系统，我们证明了一种依赖于细胞接触和可溶性因子的抑制机制。基于这些发现，我们得出结论，储存的脐带血未来可能作为间充质干细胞的潜在替代来源用于异体应用。
