In Situ Preconditioning of Human Mesenchymal Stem Cells Elicits Comprehensive Cardiac Repair Following Myocardial Infarction.
Woo-Sup SimBong-Woo ParkKiwon BanHun-Jun ParkPublished in: International journal of molecular sciences (2021)
Human bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cell-based cardiac regenerative therapy. However, their clinical use has been significantly hampered by low survival and poor retention following administration into failing hearts. Here, to improve the therapeutic effectiveness of BM-MSCs, we examined a novel therapeutic platform named in situ preconditioning in a rat myocardial infarction (MI) model. In situ preconditioning was induced by a combinatory treatment of BM-MSCs with genetically engineered hepatocyte growth factor-expressing MSCs (HGF-eMSCs) and heart-derived extracellular matrix (hdECM) hydrogel. Subsequently, our results demonstrated that in situ preconditioning with cell mixture substantially improved the survival/retention of BM-MSCs in the MI-induced rat hearts. Enhanced retention of BM-MSCs ultimately led to a significant cardiac function improvement, which was derived from the protection of myocardium and enhancement of vessel formation in the MI hearts. The results provide compelling evidence that in situ preconditioning devised to improve the therapeutic potential of BM-MSCs can be an effective strategy to achieve cardiac repair of MI hearts.
Keyphrases
- mesenchymal stem cells
- umbilical cord
- cell therapy
- bone marrow
- ischemia reperfusion injury
- left ventricular
- growth factor
- stem cells
- extracellular matrix
- endothelial cells
- heart failure
- cerebral ischemia
- oxidative stress
- randomized controlled trial
- single cell
- drug delivery
- systematic review
- high glucose
- drinking water
- high throughput
- drug induced
- childhood cancer
- diabetic rats
- tissue engineering