Silk-based Matrices and C-kit Positive Cardiac Progenitor Cells for a Cardiac Organoid: Study of an in Vivo Model
Abstract In recent years, there has been a shift from tissue engineering to the production of organoids. The latter are useful tools to study many biochemical aspects and cellular reactions while avoiding the excessive use of laboratory animals. Organoids are very interesting tools because they can replicate the cellular and extracellular environment of an organ and retain some of the properties of the organ itself. However, without an adequate network of vessels, cell masses not only fail to grow, but they may exhibit an area of necrosis, indicating a lack of oxygen and nutrients. For this reason, scientific researchers are looking for ways to create organoids that can also mimic the vascular network of the organ from which they originate. One possibility is to implant the organoids in immunocompromised animals.In the present study, we generated cardiac organoids ex vivo by seeding tyrosine protein kinase kit (c-kit)-positive cardiac progenitor cells (CPC cells) from fresh rat hearts into a rat collagen I gel. We then implanted these patches into immunosuppressed animals and compared the suitability of different silk fibroin scaffolds with three different geometries. We demonstrated that CPC cells were destroyed by CD3+ lymphocytes, that the porous and partially oriented scaffolds induced a consistent foreign body response compared to the electrospun meshes, and that CPC cells were degraded by a T-cell-mediated immune response, although the latter may be suitable for generating rat cardiac organoids.