GMP compliant production of fetal pancreas mesenchymal stem cells

IntroductionSeveral studies have suggested mesenchymal stem cells (MSCs) as a suitable source for cell therapy in diabetes. MSCs with similar characteristics have been isolated from different tissues including the pancreas. Previous studies have suggested fetal pancreatic derived MSCs (FPMSCs) as a good candidate for islet regeneration with higher potency that their adult counterparts. According to the current regulations, cell therapy products must be manufactured under the Good Manufacturing Practice (GMP) condition. Among different aspects of the GMP, developing a GMP compliant cell manufacturing protocol is the most challenging part.ObjectivesThe aim of current study was to establish a xeno-free/GMP compliant protocol for clinical grade FPMSCs manufacturing.MethodsFetal pancreata were aseptically collected from three legally aborted fetuses after obtaining informed consent from the parents. Under aseptic condition pancreas was dissected, minced and digested with animal origin free collagenase. The resultant tissue fragments were explanted in DMEM+10% Human Serum (HS). After 10 to14 days, fibroblast-like cells were harvested and passaged six times for further evaluations. FPMSCs characterization was performed by flowcytometry, Vimentin expression and differentiation capacity.ResultsFPMSCs were successfully produced from 3 consecutive fetal tissues using a xeno-free/GMP compliant protocol. Flowcytometry analysis and three-lineage differentiation capacity demonstrated that these cells have all characteristics of MSCs. We also continuously passaged samples of FPMSCs and found that they could withstand passaging up to 15 times without displaying chromosomal abnormalities or significant morphological changes.ConclusionsThe results of our study demonstrated that, it is feasible to produce scalable FPMSCs using a xeno-free/GMP compliant protocol

کلیدواژه ها:

Fetal pancreas ، Good manufacturing practice ، Mesenchymal stem cells ، Xeno-free