Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

Abstract

Healing and regeneration of bone injuries, particularly those that are associated with large bone defects, are a complicated process. There is growing interest in the application of osteoinductive and osteogenic growth factors and mesenchymal stem cells (MSCs) in order to significantly improve bone repair and regeneration. MSCs are multipotent stromal stem cells that can be harvested from many different sources and differentiated into a variety of cell types, such as preosteogenic chondroblasts and osteoblasts. The effectiveness of MSC therapy is dependent on several factors, including the differentiating state of the MSCs at the time of application, the method of their delivery, the concentration of MSCs per injection, the vehicle used, and the nature and extent of injury, for example. Tissue engineering and regenerative medicine, together with genetic engineering and gene therapy, are advanced options that may have the potential to improve the outcome of cell therapy. Although several in vitro and in vivo investigations have suggested the potential roles of MSCs in bone repair and regeneration, the mechanism of MSC therapy in bone repair has not been fully elucidated, the efficacy of MSC therapy has not been strongly proven in clinical trials, and several controversies exist, making it difficult to draw conclusions from the results. In this review, we update the recent advances in the mechanisms of MSC action and the delivery approaches in bone regenerative medicine. We will also review the most recent clinical trials to find out how MSCs may be beneficial for treating bone defects.

Synergistic effect of strontium, bioactive glass and nano‐hydroxyapatite promotes bone regeneration of critical‐sized radial bone defects

“…Incomplete regeneration of large bone segmental defects is associated with either the inadequate migration of mesenchymal stem cells (MSCs) into the defect site or the inability of the migrated MSCs to fully differentiate into osteogenic precursor cells . Differentiation of MSCs toward osteoblasts and other bone precursor cells is demanding in tissue engineering (TE) to successfully reconstruct large bone defects in vivo without any growth factors or osteogenic inducing medium .…”

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

“…One strategy to enhance the regenerative efficacy of MSCs is via osteogenic induction and pre‐differentiation (Oryan et al., ). In the present review, the evidence for osteogenic pre‐differentiation of BMSCs prior to clinical application was conflicting.…”

“…In this context, tissue engineering aims to combine and deliver the cellular (progenitor cells), extracellular (scaffolds) and/or molecular elements (growth factors) involved in physiological regenerative processes, for therapeutic applications. Specifically, regarding bone tissue engineering (BTE), this usually involves harvesting osteogenic cells from an autologous source (e.g., bone marrow, adipose tissue), their “chair‐side” manipulation or ex vivo amplification, and combination with an appropriate biomaterial scaffold for in vivo implantation (Evans et al., ; Oryan, Kamali, Moshiri, & Baghaban Eslaminejad, ). Thus, the “triad” of osteogenic cells, osteoinductive signals (growth factors released by cells), and osteoconductive scaffolds, aims to replicate the properties of AB, and alleviate the need for invasive harvesting (Oppenheimer, Mesa, & Buchman, ).…”

Hondroplastic Efficiency of Calcified Bone Matrix Produced by Original Technology

“…The most fully studied for the regeneration of bone and cartilage are BMP-2 and BMP-7, but there are reports of active participation in osteogenesis and chondrogenesis and other BMP species. (16) Two technological methods for obtaining BMPs are known: biochemical extraction from demineralized bone matrix and synthesis using genetic engineering (rhBMP). (17,18) Both methods are very laborious, expensive and require the use of acids and alkalis.…”