Advances in Mesenchymal Stem Cell-based Strategies for Cartilage Repair and Regeneration

Abstract

Significant research efforts have been undertaken in the last decade in the development of stem cell-based therapies for cartilage repair. Among the various stem cell sources, mesenchymal stem cells (MSCs) demonstrate great promise and clinical efficacy in cartilage regeneration. With a deeper understanding of stem cell biology, new therapeutics and new bioengineering approaches have emerged and showed potential for further developments. Of note, there has been a paradigm shift in applying MSCs for tissue regeneration from the use of stem cells for transplantation to the use of stem cell-derived matrix and secretome components as therapeutic tools and agents for cartilage regeneration. In this review, we will discuss the emerging role of MSCs in cartilage regeneration and the most recent advances in development of stem cell-based therapeutics for cartilage regeneration.

Stem Cells for Temporomandibular Joint Repair and Regeneration

“…Emerging findings have shed light on the diverse functional roles of stem cells, particularly MSCs in TMJ repair and regeneration, including those of replacement cell, and support cell via secretion of trophic factors [24,26,31,59]. To date, these unique properties of stem cells have yet to be fully harnessed for TMJ repair and regeneration.…”

“…Furthermore, transplanted MSCs were detected at cartilage, subchondral bone and the synovial lining at 4 weeks, providing strong evidence of MSCs involved in the cartilage and subchondral bone repair. The effects on preinduction/differentiation of MSCs on subsequent cartilage regeneration and phenotypic stability have been reported in a number of studies, as recently discussed [56][57][58][59]. It is generally accepted that pre-differentiation of stem cells helps to enhance cartilage regeneration particularly at the early stage, but may not necessarily maintain the chondrocytic phenotype and/or dictate a better regenerative outcome over a longer period [60].…”

“…With more sources of MSCs isolated from various tissues, it would be necessary to map the growth factor receptor repertoire of these cells to better customize their growth factor requirements in chondrogenesis. The myriad of secreted factors by different sources of MSCs during expansion and differentiation is likely to be different as well [59,63]. With a better understanding of MSC biology, more effective predifferentiation and conditioning strategies would be innovated for application in treatment of TMD.…”

“…Furthermore, the derivation of MSCs and chondroprogenitors from human pluripotent stem cells represents as a promising alternative to obtain "off-theshelf" ready cell source in large numbers and thus likely to overcome the impeding issues of cellular senescence of adult MSCs and donor variability [59,73]. In derivation of MSCs and chondroprogenitors from hESCs and iPSCs, several strategies including co-culture with stroma cells [107], growth factor stimulation [104,108,109], and/or cell sorting of specific populations [100,107], and even expansion of EB outgrowth [110] have been reported.…”

A Road Map to Commercialization of Cartilage Therapy in the United States of America

“…20 Recently, raw materials 21 such as cartilage matrix [22][23][24] (including decellularized cartilage [DCC] 25,26 ) and demineralized bone matrix have been used directly or combined with other biomaterials to create hybrid materials that provide biochemical and mechanical cues for the cells to differentiate. 22,[26][27][28] Some of the current products that employ this technology are DeNovo NT from Zimmer 29,30 and DeNovo Ò ET (Engineered Tissue Graft) from ISTO technologies, which obtained special rights and permission from Zimmer. 31,32 Both products employ juvenile DCC with a combination of cells and materials to treat cartilage lesions.…”