In vivo priming of human mesenchymal stem cells with hepatocyte growth factor–engineered mesenchymal stem cells promotes therapeutic potential for cardiac repair

Abstract

The clinical use of human bone marrow–derived mesenchymal stem cells (BM-MSCs) has been hampered by their poor performance after transplantation into failing hearts. Here, to improve the therapeutic potential of BM-MSCs, we developed a strategy termed in vivo priming in which BM-MSCs are primed in vivo in myocardial infarction (MI)–induced hearts through genetically engineered hepatocyte growth factor–expressing MSCs (HGF-eMSCs) that are encapsulated within an epicardially implanted 3D cardiac patch. Primed BM-MSCs through HGF-eMSCs exhibited improved vasculogenic potential and cell viability, which ultimately enhanced vascular regeneration and restored cardiac function to the MI hearts. Histological analyses further demonstrated that the primed BM-MSCs survived longer within a cardiac patch and conferred cardioprotection evidenced by substantially higher numbers of viable cardiomyocytes in the MI hearts. These results provide compelling evidence that this in vivo priming strategy can be an effective means to enhance the cardiac repair of MI hearts.

Functional enhancement strategies for immunomodulation of mesenchymal stem cells and their therapeutic application

“…Indeed, Park et al recently suggested a brand new function improvement method called in vivo priming. In their study, the authors transduced BM-MSCs to consistently secrete HGF and the engineered cells were seeded on 3D patch mixing with naïve cells resulting in the improvement of therapeutic function compared to naive MSCs [75]. Therefore, optimization of the combinatorial use of each strategy could be envisioned to maximize the therapeutic outcome of MSC therapy.…”

Recent Development in Therapeutic Cardiac Patches

“…To achieve better treatment, various methods have been developed to extend the therapeutic potential of current MSCs ( 86 ). Primed MSCs through genetically engineered hepatocyte growth factor–expressing MSCs (HGF-eMSCs) was developed by Park et al ( 45 ), showing largely improved vasculogenic ability and enhanced cell viability. After encapsulated in a cardiac patch, this kind of MSCs promoted vascular regeneration and repaired cardiac function within MI hearts.…”

Mesenchymal stem cell-derived exosome: a promising alternative in the therapy of Alzheimer’s disease

“…MSCs facilitate neurological recovery and neo-angiogenesis through the secretion of neurotrophins and angiogenesis regulatory factors [8][9][10]. The ability of immunomodulatory effect, migratory capability, and regenerative potential of MSCs are confirmed in multiple disease models, such as atopic dermatitis, myocardial infarction, traumatic brain injury, and diabetes nephropathy [11][12][13][14]. However, accumulating researches suggest that the biodistribution of MSCs in the target organs is rare, and its therapeutic effect appears to be a consequence of the paracrine action [15][16][17].…”