Application of stem cells derived from the periodontal ligament or gingival tissue sources for tendon tissue regeneration

Abstract

Tendon injuries are often associated with significant dysfunction and disability due to tendinous tissue’s very limited self-repair capacity and propensity for scar formation. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material present an alternative therapeutic option for tendon repair/regeneration that may be advantageous compared to other current treatment modalities. The MSC delivery vehicle is the principal determinant for successful implementation of MSC-mediated regenerative therapies. In the current study, a co-delivery system based on TGF-β3-loaded RGD-coupled alginate microspheres was developed for encapsulating periodontal ligament stem cells (PDLSCs) or gingival mesenchymal stem cells (GMSCs). The capacity of encapsulated dental MSCs to differentiate into tendon tissue was investigated in vitro and in vivo. Encapsulated dental-derived MSCs were transplanted subcutaneously into immunocompromised mice. Our results revealed that after 4 weeks of differentiation in vitro, PDLSCs and GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited high levels of mRNA expression for gene markers related to tendon regeneration (Scx, DCn, Tnmd, and Bgy) via qPCR measurement. In a corresponding in vivo animal model, ectopic neo-tendon regeneration was observed in subcutaneous transplanted MSC-alginate constructs, as confirmed by histological and immunohistochemical staining for protein markers specific for tendons. Interestingly, in our quantitative PCR and in vivo histomorphometric analyses, PDLSCs showed significantly greater capacity for tendon regeneration than GMSCs or hBMMSCs (P<0.05). Altogether, these findings indicate that periodontal ligament and gingival tissues can be considered as suitable stem cell sources for tendon engineering. PDLSCs and GMSCs encapsulated in TGF-β3-loaded RGD-modified alginate microspheres are promising candidates for tendon regeneration.

Tendon Derived Stem Cells Promote Platelet-Rich Plasma Healing in Collagenase-Induced Rat Achilles Tendinopathy

“…A wide range of donor cell types have been used to promote tendon healing in pre-clinical studies, including bone marrow-derived mesenchymal stem cells (BMSCs) [3,4,5], periodontal ligament or gingival tissue [6], dermal fibroblast [7], tenocytes [8], peripheral blood-derived MSCs [9,10] and embryonic stem cell derived MSCs (ESC-MSCs) [11]. Each cell source has its limitations including inferior proliferation, differentiation and collagen production abilities of tenocytes [12,13,14,15], risk of teratoma formation of ESCs as well as risk of ectopic bone [3] and tumor induction [16] of BMSCs when using a certain scaffold.…”

Effects of Sirtuin 1 on the proliferation and osteoblastic differentiation of periodontal ligament stem cells and stem cells from apical papilla

“…However, little is known about which cell type acts as the origin of dental stem cells and how they differentiate into functional cells. Certain dental stem cells [periodontal ligament stem cells (PDLSCs) and stem cells from apical papilla (SCAPs)] have been verified to have variable differentiation potentials and thus can be used in oral tissue engineering (Sumita et al, 2006;Moshaverinia et al, 2014). The osteoblastic differentiation abilities of PDLSCs and SCAPs have been confirmed and their functions in promoting osteogenesis have also been verified in multiple studies (Cate, 1996;Yang et al, 2009).…”

“…To our knowledge, periodontal ligament cells are principal functional cells, regenerating and reconstructing the periodontal tissues (Moshaverinia et al, 2014). The periodontal ligament is a source of pluri-potent cells and molecular factors that control cellular events in the periodontal tissues.…”

Transplantation of Adipose-Derived Stem Cells in Stroke

“…The reported sources of mesenchymal stem cells include bone marrow (Skvortsova et al 2008), adipose tissue (Gutierrez-Fernandez et al 2013a), embryo (Liu et al 2009), placenta (Kranz et al 2010), dental pulp and periodontal ligament (Moshaverinia et al 2014;Vasandan et al 2014). Other sources, including palatine tonsil (Janjanin et al, 2008), dermis (Feisst et al 2014), and skeletomuscular system (Aydin et al 2014;Mason et al 2014), have also been reported.…”