tailieunhanh - báo cáo hóa học:" Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs"

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí sinh học đề tài : Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs | Chen et al. Journal of Translational Medicine 2011 9 47 http content 9 1 47 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs 1 2 1 1 4 Tian Sheng Chen Fatih Arslan Yijun Yin Soon Sim Tan Ruenn Chai Lai Andre Boon Hwa Choo Jayanthi Padmanabhan4 Chuen Neng Lee5 Dominique PV de Kleijn2 6 and Sai Kiang Lim1 5 Abstract Background Exosomes or secreted bi-lipid vesicles from human ESC-derived mesenchymal stem cells hESC-MSCs have been shown to reduce myocardial ischemia reperfusion injury in animal models. However as hESC-MSCs are not infinitely expansible large scale production of these exosomes would require replenishment of hESC-MSC through derivation from hESCs and incur recurring costs for testing and validation of each new batch. Our aim was therefore to investigate if MYC immortalization of hESC-MSC would circumvent this constraint without compromising the production of therapeutically efficacious exosomes. Methods The hESC-MSCs were transfected by lentivirus carrying a MYC gene. The transformed cells were analyzed for MYC transgene integration transcript and protein levels and surface markers rate of cell cycling telomerase activity karyotype genome-wide gene expression and differentiation potential. The exosomes were isolated by HPLC fractionation and tested in a mouse model of myocardial ischemia reperfusion injury and infarct sizes were further assessed by using Evans blue dye injection and TTC staining. Results MYC-transformed MSCs largely resembled the parental hESC-MSCs with major differences being reduced plastic adherence faster growth failure to senesce increased MYC protein expression and loss of in vitro adipogenic potential that technically rendered the transformed cells as non-MSCs. Unexpectedly exosomes from MYC-transformed MSCs were able to reduce relative infarct size in a .