Cardiac tissue regeneration by microfluidic generated cardiac cell-laden calcium alginate microgels and mesenchymal stem cell extracted exosomes on myocardial infarction model.

Regenerative medicine is one of the effective approaches for myocardial infarcted (MI) tissue due to the low capacity of heart for regeneration. However, cell therapy with local administration has shown poor cell retention in the targeted area and limited engraftment capacity at the intended location, resulting in inadequate tissue regeneration. The present study involves mesenchymal stem cell-derived exosomes and encapsulated cells in small and injectable calcium alginate microgels by a specialized microfluidic device to decrease inflammation and increase cell retention in the infarcted tissue. The results have shown that our microfluidic system can produce monodisperse cardiac cell-laden alginate microgels within the size range of <100 μm that are easily injectable. Our in vivo findings on the MI rat model demonstrated that the combination of cardiac cell-laden calcium alginate microgels with mesenchymal stem cells derived exosomes resulted in a higher increase in echocardiography, heart-specific gene expressions, and cardiac markers results compared to the other groups. However, the administration of exosomes or cardiac cells separately has shown a small amount of regeneration. Encapsulating cardiac cells of specific sizes along with exosomes produced from mesenchymal stem cells can be potentially applied as an effective method for regenerating the myocardium following infarction.