Regeneration of different types of tissues depends on the interplay of stem cells-laden constructs and microenvironments in vivo

摘要

The ability of repair and regeneration of tissues or organs has been significantly improved by using biomaterials-based constructs. Our previous studies found the regeneration of both articular cartilage and subchondral bone by implantation of a poly(lactide-co-glycolide) (PLGA)/fibrin gel/bone marrow stem cells (BMSCs)/(lipofectamine/pDNA-transforming growth factor (TGF)-beta 1) construct in vivo, without the step of pre-induced differentiation of the laden stem cells in vitro. To substantiate the ability to regenerate multi-types of tissues by the same constructs, in this study the constructs were implanted into three types of tissues or tissue defects in vivo, including subcutaneous fascia layer, and ear cartilage and eyelid tarsal plate defects. The ear cartilage and eyelid tarsal plate defects were fully regenerated 8 w post-implantation, showing a similar morphology to the corresponding native tissues. In the neo ear cartilage, abundant chondrocytes with obvious lacunas and cartilage-specific extracellular matrices (ECMs) were found. Neo eyelid tarsal plate with mature meibomian gland acinar units was regenerated. Furthermore, expressions of the ECMs-specific genes and proteins, as well as the cell behavior modulatory factors, Sry related HMG box 9 (Sox9) and TGF-beta 1 were significantly up-regulated in the regenerated ear cartilages and eyelid tarsal plate than those in the subcutaneously implanted constructs, which were filled with fibrocytes, inflammatory cells, obvious vascularization and slight ECMs deposition. These results confirm firmly the ability to regenerate multi-types of tissues by a stem cells-laden construct via adapting to the microenvironments of corresponding tissues.