Implementation of Endogenous and Exogenous Mesenchymal Progenitor Cells for Skeletal Tissue Regeneration and Repair

Abstract

Harnessing adult mesenchymal stem/progenitor cells to stimulate skeletal tissue repair is a strategy that is being actively investigated. While scientists continue to develop creative and thoughtful ways to utilize these cells for tissue repair, the vast majority of these methodologies can ultimately be categorized into two main approaches: (1) Facilitating the recruitment of endogenous host cells to the injury site; and (2) physically administering into the injury site cells themselves, exogenously, either by autologous or allogeneic implantation. The aim of this paper is to comprehensively review recent key literature on the use of these two approaches in stimulating healing and repair of different skeletal tissues. As expected, each of the two strategies have their own advantages and limitations (which we describe), especially when considering the diverse microenvironments of different skeletal tissues like bone, tendon/ligament, and cartilage/fibrocartilage. This paper also discusses stem/progenitor cells commonly used for repairing different skeletal tissues, and it lists ongoing clinical trials that have risen from the implementation of these cells and strategies. Lastly, we discuss our own thoughts on where the field is headed in the near future.

Proteomic Comparison of Bone Marrow Derived Osteoblasts and Mesenchymal Stem Cells

“…Both osteoblasts and MSCs have been tried in the treatment of human disease, including cell therapy and the use of conditioned medium [ 48 , 49 , 50 ]. Conditioned medium derived from MSC-differentiated osteoblasts seems to improve engraftment of cord blood progenitors [ 51 ], stem cell derived exosomes can improve osteoporosis by promoting osteoblast proliferation [ 52 ], and injection of in vitro expanded osteoblasts has been tried in the treatment of fractures [ 9 , 53 ], as well as osteonecrosis [ 54 ].…”

Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration

“…Scaffolds used in tendon TE are considered as temporarily ECM replacement whose aim is guiding the neo-formation and the deposition of ECM while parallelly degrading throughout the regeneration process [ 20 ]. These could be addressed through two complementary pathways including the activation of endogenous and/or exogenous cell regeneration mechanisms that could be driven by the functionalization of the scaffold with stem and/or progenitor cells [ 21 ]. Therefore, scaffolds are frequently utilized in combination with growth factors and stem cells whose aim is to support the tissue healing both mechanically and biologically.…”

Tendon Healing Response Is Dependent on Epithelial–Mesenchymal–Tendon Transition State of Amniotic Epithelial Stem Cells

“…Key inflammatory mediators-such as cytokines, nitric oxide, prostaglandins, and lipoxins-play crucial parts in dysregulating the extracellular matrix (ECM) within tendinopathy [11]. In tendons, during spontaneous healing, repairing and remodeling may take several months [13], and their poor intrinsic regenerative potential leads to a repaired tissue that is consistently different from the native one [14]. Current tendinopathy therapeutic strategies foresee the use of conservative approaches or surgical repair using autografts, allografts, and xenografts, which have a limited success [15].…”