tailieunhanh - Báo cáo sinh học: "Comparative study of clinical grade human tolerogenic dendritic "

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Comparative study of clinical grade human tolerogenic dendritic | Naranjo-Gómez et al. Journal of Translational Medicine 2011 9 89 http content 9 1 89 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access Comparative study of clinical grade human tolerogenic dendritic cells 1 1 s v-x 1 2 2 1 11 M Naranjo-Gómez D Raich-Regué C Onate L Grau-López C Ramo-Tello R Pujol-Borrell E Martinez-Caceres 1 and Francesc E Borràs1 t Abstract Background The use of tolerogenic DCs is a promising therapeutic strategy for transplantation and autoimmune disorders. Immunomodulatory DCs are primarily generated from monocytes MDDCs for in vitro experiments following protocols that fail to fulfil the strict regulatory rules of clinically applicable products. Here we compared the efficacy of three different tolerance-inducing agents dexamethasone rapamycin and vitamin D3 on DC biology using GMP Good Manufacturing Practice or clinical grade reagents with the aim of defining their use for human cell therapy. Methods Tolerogenic MDDCs were generated by adding tolerogenic agents prior to the induction of maturation using TNF-a IL-p and PGE2. We evaluated the effects of each agent on viability efficiency of differentiation phenotype cytokine secretion and stability the stimulatory capacity of tol-DCs and the T-cell profiles induced. Results Differences relevant to therapeutic applicability were observed with the cellular products that were obtained. VitD3-induced tol-DCs exhibited a slightly reduced viability and yield compared to Dexa-and Rapa-tol-DCs. Phenotypically while Dexa-and VitD3-tol-DCs were similar to immature DCs Rapa-tol-DCs were not distinguishable from mature DCs. In addition only Dexa-and moderately VitD3-tol-DCs exhibited IL-10 production. Interestingly in all cases the cytokine secretion profiles of tol-DCs were not modified by a subsequent TLR stimulation with LPS indicating that all products had stable phenotypes. Functionally clearly reduced alloantigen T cell proliferation was induced by tol-DCs obtained .