Histocompatibility testing of cultivated human bone marrow stromal cells - a promising step towards pre-clinical screening for allogeneic stem cell therapy.
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.
Koppula
Purushotham Reddy
PR
C-TRACER, Hyderabad Eye Research Foundation, L.V. Prasad Eye Institute, Hyderabad, India.
Chelluri
Lakshmi Kiran
LK
Polisetti
Naresh
N
Vemuganti
Geeta K
GK
D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D017635:Clonal Anergy; D006650:Histocompatibility Testing; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D011446:Prospective Studies; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism