Wolbank Susanne, Peterbauer Anja, Fahrner Marc, Hennerbichler Simone, van Griensven Martijn, Stadler Guido, Redl Heinz, Gabriel Christian
Red Cross Blood Transfusion Service of Upper Austria, Linz, Austria.
Tissue Eng. 2007 Jun;13(6):1173-83. doi: 10.1089/ten.2006.0313.
Bone marrow-derived mesenchymal stem cells (BMSCs) have been used for allogeneic application in tissue engineering but have certain drawbacks. Therefore, stem cells (SC)s derived from other adult tissue sources have been considered as an alternative. However, there is only limited knowledge on their immunomodulatory properties. The aim of our study was to compare the immunomodulatory potential of human amniotic mesenchymal and human amniotic epithelial cells with that of human adipose-derived SCs under identical experimental conditions. We have demonstrated a dose-dependent inhibition of peripheral blood mononuclear cell (PBMC) immune responses in mixed lymphocyte reactions (up to 66-93% inhibition) and phytohemagglutinin activation assays (up to 67-96% inhibition). The lowest SC-to-PBMC ratio able to inhibit PBMC proliferation significantly was 1:8. Subcultivation (passage 2-6) did not alter immunoinhibitory properties, whereas cryopreservation significantly reduced the immunomodulatory potential. Using transwell systems, we have demonstrated an inhibition mechanism that is dependent on cell contact. Additionally, in coculture with allogeneic PBMCs, SCs were well tolerated and at most provoked mild alloreactions in singular cases. This study demonstrates, for the first time, contact- and dose-dependent immunosuppression of mesenchymal and epithelial amniotic SC populations, as well as of adipose tissue-derived SCs. All three cell types may be considered as possible alternatives to BMSCs for allogeneic application in tissue engineering.
骨髓间充质干细胞（BMSCs）已被用于组织工程中的异体应用，但存在一定缺点。因此，源自其他成人组织来源的干细胞（SCs）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。我们研究的目的是在相同实验条件下比较人羊膜间充质细胞和人羊膜上皮细胞与人脂肪来源的SCs的免疫调节潜力。我们已经证明在混合淋巴细胞反应（抑制率高达66 - 93%）和植物血凝素激活试验（抑制率高达67 - 96%）中，外周血单个核细胞（PBMC）免疫反应受到剂量依赖性抑制。能够显著抑制PBMC增殖的最低SCs与PBMC比例为1:8。传代培养（第2 - 6代）未改变免疫抑制特性，而冷冻保存显著降低了免疫调节潜力。使用Transwell系统，我们证明了一种依赖细胞接触的抑制机制。此外，在与异体PBMC共培养时，SCs耐受性良好，在个别情况下最多引发轻度同种异体反应。本研究首次证明了羊膜间充质和上皮SCs群体以及脂肪组织来源的SCs存在接触依赖性和剂量依赖性免疫抑制。所有这三种细胞类型都可被视为在组织工程异体应用中替代BMSCs的可能选择。
