Comparative regenerative properties of mesenchymal stem cells isolated from MRL (Murphy Roths Large) versus C57Bl6 mice

Introduction Adult Mammals are unable to regenerate their injuried myocardium by contrast to Zebrafish or MRL mice. While myocardial repair has been shown after cryoinjury in MRL mice, it failed after coronary ligation leading to ischemic injury. This underlies the impact of the inflammatory environment on the intrinsic regenerative potential of MRL stem cells. Mesenchymal stem cells (MSC) administered as cardiac therapy have emerged as breakthrough immunomodulative and cytoprotective treatments for myocardial infarction. Objective to compare the intrinsic regenerative properties of MSC derived from C57BL/6 (MSC-BL6) and MRL (MSC-MRL) mice in an ex vivo myocardial ischemia-reperfusion (IR) injury model and decipher the underlying mechanisms. Methods FACS analysis allowed characteristic phenotyping of MSC isolated from C57BL/6 (MSC-B6) or MRL (MSC-MRL) murine bone marrow. Their differentiation potential into chondrocytes, osteoblasts and adipocytes upon inductive conditions was studied. Their migration capacities were evaluated using the in vitro scratch wound healing assay. Infarct size was measured in mouse hearts subjected to ex vivo 30 min-ischemia and 1 hour-reperfusion and treated by MSCs. Results In vitro, MSC-MRL showed a significantly higher migration potential than MSC-B6 in accordance with reduced expression levels of E-cadherin and cadherin 11 adhesion molecules. Using MRL-MSC conditioned medium, we demonstrated an increased migration capacity of MSC-B6 suggesting that the MRL-MSC release a soluble factor responsible for their potent homing potential to the wound site. Injected during reperfusion, MSC-MRL were able to protect the injured myocardium more efficiently than MSC-B6 in the ex vivo IR model (MSC-MRL: 47.18 ± 0.66%, n = 3 vs MSC-B6: 56.36 ± 3.17%, n = 3). Conclusion MSC-MRL have superior cardioprotective effects for the treatment of IR injury compared to MSC-B6 probably due to higher migration capacities and specific regenerative secretome.