Conditioned MSCs patched onto damaged hearts boost healing

Written by Alexander Marshall

Researchers have created a patch of conditioned mesenchymal stem cells that can survive for 8 weeks and contribute to healing a damaged heart in rats.

Researchers from City University of Hong Kong (Kowloon, Hong Kong) have produced a patch of conditioned mesenchymal stem cells (MSCs) that can contribute to heart regeneration.

Normal MSCs fail to persist beyond 3—4 days when injected into cardiac tissue; however, the findings, described in Science Advances, tested a novel patch in rats and demonstrated  cells surviving for up to 8 weeks, resulting in better cardiac function.

Ban Kiwon (City University of Hong Kong) led the team that produced the new patch of cells. By 3D printing a bioink composed of porcelain extra-cellular matrix and genetically modified MSCs, Kiwon was able to demonstrate an increase in cardiac function and angiogenesis, while simultaneously showing a decrease in tissue fibrosis.

“We found that the primed cells can survive even after 8 weeks in the patch after implantation to the heart. Also, there is a significant improvement in cardiac function as well as vessel regeneration comparing to the unprimed cells,” explained Kiwon.

Heart tissue has been a persistent nuisance for the regenerative medicine field due to a suspected lack of innate stem cells and regenerative potential; however, the concept of treatments utilizing other therapeutic cell types, such as MSCs, has gained popularity. Unfortunately, the tissue environment is harsh for the MSCs so Kiwon examined a strategy he dubbed ‘in vivo priming’, that involved conditioning the cells to survive longer term.

“Priming, or called preconditioning, is a common strategy to empower the cells. The cells are educated through certain stimulations and when they are relocated to tough environments, they are much stronger against bad conditions and they will know how to react because of their previous experiences,” commented Kiwon.

Kiwon seeded human bone marrow-derived MSCs with or without genetically engineered MSCs that expressed human hepatocyte growth factor (HGF) — a protein with known roles in regeneration, wound healing and survival. Those MSCs that were seeded into the scaffold with their genetically engineered counterparts were able to persist and aid healing, which Kiwon concluded was the result of the persistent exposure to HGF.

“Our team is the very first to achieve priming in hearts in vivo. But more importantly, by showing that in vivo priming of human bone marrow-derived MSCs can enhance the therapeutic potential for cardiac repair, we hope our study can bring significant implications for related stem cell therapy in future,” stated Kiwon.

So far, the patch has only been tested in rat models, so the therapy will need to be trialed with human cardiac tissue to demonstrate its effectiveness before progressing further.

Sources: Park BW, Jung SH, Das S et al. In vivo priming of human mesenchymal stem cells with hepatocyte growth factor—engineered mesenchymal stem cells promotes therapeutic potential for cardiac repair. Sci. Adv. 6(13), eaay6994 (2020);