Tracking the Fate of Muscle-derived Stem Cells: an Insight into the Distribution and Mode of Action

PURPOSE: To examine the fate of muscle-derived stem cells (MDSC) after injection into different host conditions and provide an insight for their mechanism of action. MATERIALS AND METHODS: MDSCs differentiated in vitro towards the endothelial lineage and transfected with lentivirus tagged with green fluorescent protein (GFP) were injected into two animal models mimicking vascular diseases: hindlimb ischemia and carotid injury models. Injected cells were tracked at the site of injection and in remote organs by harvesting the respective tissues at different time intervals and performing immunofluorescent histological analyses. Stem cell survival was quantified at the site of injection for up to 4 weeks. RESULTS: MDSCs were successfully tagged with fluorescent material GFP and showed successful implantation into the respective injection sites. These cells showed a higher affinity to implant in blood vessel walls as shown by double fluorescent co-stain with CD31. Quantification of stem cell survival showed a timede pendent decrease from day 3 to 4 weeks (survival rate normalized against day 3 was 72.0% at 1 week, 26.8% at 2 weeks and 2.4% at 4 weeks). Stem cells were also found in distant organs, especially the kidneys and liver, which survived up to 4 weeks. CONCLUSION: MDSCs were successfully tracked in different vascular disease models, and their fate was assessed in terms of cell survival and distribution. Better understanding of the donor cell properties, including their interaction with the host conditions and their mechanism of action, are needed to enhance cell survival and achieve improved outcomes.