An Improved Transplantation Strategy for Mouse Mesenchymal Stem Cells in an Acute Myocardial Infarction Model

Abstract

To develop an effective therapeutic strategy for cardiac regeneration using bone marrow mesenchymal stem cells (BM-MSCs), the primary mouse BM-MSCs (1st BM-MSCs) and 5th passage BM-MSCs from β-galactosidase transgenic mice were respectively intramyocardially transplanted into the acute myocardial infarction (AMI) model of wild type mice. At the 6th week, animals/tissues from the 1st BM-MSCs group, the 5th passage BM-MSCs group, control group were examined. Our results revealed that, compared to the 5th passage BM-MSCs, the 1st BM-MSCs had better therapeutic effects in the mouse MI model. The 1st BM-MSCs maintained greater differentiation potentials towards cardiomocytes or vascular endothelial cells in vitro. This is indicated by higher expressions of cardiomyocyte and vascular endothelial cell mature markers in vitro. Furthermore, we identified that 24 proteins were down-regulated and 3 proteins were up-regulated in the 5th BM-MSCs in comparison to the 1st BM-MSCs, using mass spectrometry following two-dimensional electrophoresis. Our data suggest that transplantation of the 1st BM-MSCs may be an effective therapeutic strategy for cardiac tissue regeneration following AMI, and altered protein expression profiles between the 1st BM-MSCs and 5th passage BM-MSCs may account for the difference in their maintenance of stemness and their therapeutic effects following AMI.

Improved Proliferation and Differentiation of Bone Marrow Mesenchymal Stem Cells Into Vascular Endothelial Cells With Sphingosine 1-Phosphate

“…Some studies showed that the capability of MSC differentiation reduced gradually after passaged [5,20]. It also had been found that PR-MSCs improved cardiac function in mice with myocardial infarction (MI) [6,21]. But it was difficult to obtain sufficient PR-MSCs in clinical application [22].…”

Harvesting the Benefits of Understanding Cancer with the Use of ?Shuttle? Era Technology- Cellular Survival Strategies and Tissue Engineering Via Grafting of Genetically Immortalized Autologous Cells

“…Doubtlessly this would be of great assistance in replacing large zonal areas of damaged cardiomyocytes within the heart. Having said this, recently mouse bone marrow mesenchymal stem cells have been experimentally transplanted into an acute damage heart model [38]. Interestingly, primary mesenchymal stem cells fared much better at cardiac regeneration than passaged stem cells.…”

“…Also problems occur with respect to limited stem cell survival upon their implantation into areas of damaged heart tissue due limiting survival as outlined above (35). Curiously too, stem cell manipulations are technique sensitive in that primary harvested mesenchymal stem cells are better equipped to be employed in cardiac regeneration than stem cells that have been passaged ex vivo as described in the previous section [38]. These negative points serve to indicate that working with stem cells is by no means predictable or technically straightforward.…”

Multifunctional Biomimetic Scaffolds Tailored for Cardiac Regeneration

“…23 The finding that other stem cell populations, like bone marrow derived stem cells and mesenchymal stem cells can differentiate into cardiomyocytes has prompted studies on the influence of these cells when directly injected into a defunct rat myocardium and were found to increase the functionality of the left ventricle post-MI. 24,25 There have been many cell injection therapy clinical trials in the past few years using, e.g. different stem cells, and smooth muscle cells.…”