Regeneration of temporomandibular joint using in vitro human stem cells: A review

Abstract

Temporomandibular joint disorders (TMDs) range from gross anatomic deformities of the disc and hard tissue to functional disturbances. Traditional treatment of TMDs includes physical therapy, use of appliances, pharmacological, surgical and psychological interventions. However, during the late stage of TMDs, conventional management often results in inadequate relief of symptoms. Stem cell-based tissue regeneration has been studied extensively in joint regeneration, including the Temporomandibular Joint (TMJ). This study aims to review the potential of various human stem cells (HSC) for the regeneration of the TMJ. In vitro studies using human mesenchymal stem cells cultured under different conditions to evaluate regeneration of TMJ related structures were searched on PubMed, EMBASE, Cochrane, and Web of Science up to March 2020. In vitro studies utilized several different types of stem cells under varying conditions. Increased osteogenesis and/ or chondrogenesis were noted with stem cell interventions compared to control groups on Alkaline Phosphatase (ALP) activity, Col-I, Col-II, Col-X, RUNX2, LPL, and Aggrecan mRNA expression. This review emphasizes the potential of stem cell therapies in the regeneration of TMJ-related structures. However, further in vivo studies are required to evaluate the efficacy and safety of these therapies in humans. K E Y W O R D S in vitro, mesenchymal stem cells, review, stem cell therapies, temporomandibular disorders, temporomandibular joint 1 | INTRODUCTION The temporomandibular joint (TMJ) is a complex synovial joint with a unique articulation between the temporal glenoid fossa and the mandibular condyle, which are separated by an articular disc composed of avascular and non-innervated dense fibrous connective tissue with a varying amount of fibrocartilage. The articular disc divides the TMJ cavity into upper and lower chambers. Gliding movement occurs in the upper chamber during the maximal mouth opening, while the lower chamber function primarily as a hinge or rotary movement in the early opening. Because the TMJ has a hinge and sliding movable socket, it is classified as ginglymoarthrodial a joint. The TMJ is surrounded by a fibrous connective tissue capsule attached to muscles and tendons. The capsule is lined by a synovium This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Insights into skeletal stem cells

“…Stem cell-based temporomandibular joint regeneration is extensively studied. 176 – 178 Potential of various human stem cells to regenerate TMJ has been explored and in vivo studies are expected. 176 Notably, fibrocartilage stem cells (FCSCs) at the superficial zone of the condylar cartilage were identified with αSMA-Cre ERT2 and they generated and maintained the cartilage structure.…”

“… 176 – 178 Potential of various human stem cells to regenerate TMJ has been explored and in vivo studies are expected. 176 Notably, fibrocartilage stem cells (FCSCs) at the superficial zone of the condylar cartilage were identified with αSMA-Cre ERT2 and they generated and maintained the cartilage structure. A single FCSC was sufficient to form cartilage anlage, and recapitulated endochondral ossification to form bone and support hematopoiesis in vivo.…”

Autologous Stem Cells Transplants in the Treatment of Temporomandibular Joints Disorders: A Systematic Review and Meta-Analysis of Clinical Trials

“…These authors suggested that the place of origin of the collected cells, the type of joint into which they will be administered, as well as the intra-articular co-application of other substances may affect the properties and therapeutic effect of stem cells [ 50 ]. The regenerative potential for the structures of the temporomandibular joint was confirmed in in vitro studies [ 106 ]. Intra-articular stem cell injections have repeatedly shown good results in animal studies [ 107 , 108 , 109 , 110 , 111 ].…”

Advances in Tissue Engineering of the Temporomandibular Joint Disc: An Overview of Current Status and Future Directions

“…In addition, various growth factors such as bone morphogenetic protein 2 (BMP-2), connective tissue growth factor (CTGF), and platelet-rich plasma (PRP), epidermal growth factor, interleukin 1, and tumor necrosis factor alpha used alone or in combination with cells and/or scaffolds have a role in proliferation and production of collagen and glycosaminoglycans (GAG), and hence, they have been used to regenerate TMJ discal tissues too [31]. Among these growth factors, PRP has been widely used due to the presence of various growth factors in it [59]. In a study to explore the role of PRP, the regeneration of hyaline and fibrocartilage was higher in surgical defects treated with PRP than in the control group [60].…”