Abstract
Reconstructing functional volumetric tissue in vivo following implantation remains a critical challenge facing cell-based approaches. Several pre-vascularization approaches have been developed to increase cell viability following implantation. Structural and functional restoration was achieved in a preclinical rodent tissue defect; however, the approach used in this model fails to repair larger (>mm) defects as observed in a clinical setting. We propose an effective cell delivery system utilizing appropriate vascularization at the site of cell implantation that results in volumetric and functional tissue reconstruction. Our method of multiple cell injections in a progressive manner yielded improved cell survival and formed volumetric muscle tissues in an ectopic muscle site. In addition, this strategy supported the reconstruction of functional skeletal muscle tissue in a rodent volumetric muscle loss injury model. Results from our study suggest that our method may be used to repair volumetric tissue defects by overcoming diffusion limitations and facilitating adequate vascularization.
Highlights
Cell-based therapies in tissue engineering (TE) and regenerative medicine (RM) provide promise to restore normal functions of damaged and injured tissues and organs[1]
To investigate the feasibility of restoring volumetric muscle tissues by multiple cell injections in a progressive manner, C2C12 cells were subcutaneously injected in athymic mice, and the volume of the newly formed tissues was measured at pre-determined injection points for comparison
In hematoxylin and eosin (H&E) and masson’s trichrome (MT) staining images, increase in the volume of reconstructed tissue formation was notable between 2 and 4 cell injections, but no significant size difference was observed beyond 4 cell injections
Summary
Cell-based therapies in tissue engineering (TE) and regenerative medicine (RM) provide promise to restore normal functions of damaged and injured tissues and organs[1]. Repair of larger tissue defects requires implantation of large, volumetric engineered tissue constructs or implantation of high-dose cells[12,13,14] to restore normal functions. Under such conditions, oxygen transport to all of the implanted cells is difficult. This work shows that repeated cell-sheet transplantation at time intervals of 1–2 days can generate vascularized cardiomyocyte sheets in vivo While those strategies is a promising approach in terms of addressing volumetric tissue defects, several issues such as delayed perfusion, numerous surgical interventions, and inefficient cell grafting within the vascularized explanted tissue must be addressed before clinical use[15]. This cell delivery technique using C2C12 cells and human muscle progenitor cells (hMPCs) was applied to a rodent volumetric muscle loss (VML) model; histological and functional recovery was evaluated to determine the possibility for applications to treat critical-size muscle defects
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