Clinical grade production of Mesenchymal Stem Cells derived from Embryonic Stem Cells (ESC-MSC) having Therapy Effect to a Rat Model of Myocardial Infarction

Abstract

Backgroud Human embryonic stem cell (hESC) have great potentiality to stem cell therapy. However, treating embryonic stem cell itself to patient has the possibility of suffering harm because of tumorigenicity and immune rejection. In order to overcome these risks, hESCs were induced to other lineage usually for applying stem cell therapy to human. Mesenchymal Stem Cells induced from ESC (hESC-MSCs) have the capability to self-renew and differentiate into various types of cell

Methods and results Working in cGMP facility was proved that hESC-MSC is culturing at aseptic condition. An efficient method of building up hESC-MSCs without any xeno factors during culture in cGMP facility was developed. we confirmed hESC with non xeno factor was growth well. Then via EB stage, MSCs was differentiated completely form ESC. Moreover, we documented and standardized the derivation and culture of MSCs for establishing stable cell line. we culture hESC on extracellular matrix instead of feeder cell and serum free media was used without xeno factors. Our derived MSCs from ESCs were expressed CD44, CD73, CD90, CD29 and CD105 as MSCs positive markers and not expressed MSCs negative markers, CD34 and CD45. We also studied therapeutic efficacy of hESC-MSCs in vivo. To reduce difference between entities, we use inbred rat (F344) and induce a rat model of Myocardial Infarction (MI). We injected cell to MI model at periinfarct zone. Through various analyses, we demonstrated that heart function of cell transplantation group in MI model was better condition than group with PBS.

Conclusion Our established method induced MSCs from ESCs in cGMP facility could overcome limitation of other derivation methods and get high purity of yield. Moreover, our method is easy, simple. With animal experiment, we suggested hESC-MSCs is suitable to apply clinical trial about MI.