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培养的人骨髓基质细胞的组织相容性检测——迈向异基因干细胞治疗临床前筛查的有希望的一步。

Histocompatibility testing of cultivated human bone marrow stromal cells - a promising step towards pre-clinical screening for allogeneic stem cell therapy.

作者信息

Koppula Purushotham Reddy, Chelluri Lakshmi Kiran, Polisetti Naresh, Vemuganti Geeta K

机构信息

C-TRACER, Hyderabad Eye Research Foundation, L.V. Prasad Eye Institute, Hyderabad, India.

出版信息

Cell Immunol. 2009;259(1):61-5. doi: 10.1016/j.cellimm.2009.05.014. Epub 2009 Jun 6.

Abstract

Mesenchymal stem cells (MSCs) lack major histocompatibility complex (MHC)-II and only show minimal MHC-I expression. Despite MSCs demonstrating T-cell anergy, there are no established methods to evaluate their suitability. It is crucial to evaluate the complete mismatch of MHC compatibility in view of the hypo-immunogenic nature and immunomodulatory properties of MSCs with respect to their proliferation potential (PP) and utility in terms of passage number. With bone marrow (BM) being the major source of MSCs, the use of these cells becomes even more complicated, due to many other receptors coming to fore and triggering alternative pathways. This prospective study included five BM aspirates for MSC cultures and five allogeneic peripheral blood mono nuclear cells (PBMNCs) from healthy volunteers. MHC compatibility was assessed by polymerase chain reaction-sequence specific primer (PCR-SSP). The PP and a T-cell response to MSCs was addressed in mixed cultures and evaluated on the basis of their stimulation index (SI). Allogeneic circulatory antibodies against the donor MSCs was performed by cytotoxicity assay. The PP of MSCs during interactions with PBMNCs (T-cells) demonstrated T-cell anergy and the response to circulatory antibodies was minimal, in consonance with other published reports. Although, the results are encouraging for potential clinical application of MSC transplantation, autologous is always preferable to allogeneic, at least until the long-term safety of these cells is established in clinical trials.

摘要

间充质干细胞(MSCs)缺乏主要组织相容性复合体(MHC)-II,仅表现出极低水平的MHC-I表达。尽管MSCs能诱导T细胞无能,但尚无既定方法来评估其适用性。鉴于MSCs的低免疫原性本质及其免疫调节特性,考虑到其增殖潜能(PP)和传代次数方面的效用,评估MHC相容性的完全不匹配至关重要。由于骨髓(BM)是MSCs的主要来源,使用这些细胞变得更加复杂,因为许多其他受体出现并触发替代途径。这项前瞻性研究纳入了5份用于MSCs培养的骨髓抽吸物和5份来自健康志愿者的异体外周血单个核细胞(PBMNCs)。通过聚合酶链反应-序列特异性引物(PCR-SSP)评估MHC相容性。在混合培养中研究了MSCs的PP和对MSCs的T细胞反应,并根据刺激指数(SI)进行评估。通过细胞毒性试验检测针对供体MSCs的异体循环抗体。与其他已发表的报告一致,MSCs与PBMNCs(T细胞)相互作用期间的PP表现出T细胞无能,并且对循环抗体的反应极小。尽管如此,这些结果对于MSCs移植的潜在临床应用是令人鼓舞的,但至少在临床试验确定这些细胞的长期安全性之前,自体移植总是比异体移植更可取。

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