Temporomandibular Joint Osteoarthritis: Regenerative Treatment by a Stem Cell Containing Advanced Therapy Medicinal Product (ATMP)—An In Vivo Animal Trial

Abstract

Temporomandibular joint osteoarthritis (TMJ-OA) is a chronic degenerative disease that is often characterized by progressive impairment of the temporomandibular functional unit. The aim of this randomized controlled animal trial was a comparative analysis regarding the chondroregenerative potency of intra-articular stem/stromal cell therapy. Four weeks after combined mechanical and biochemical osteoarthritis induction in 28 rabbits, therapy was initiated by a single intra-articular injection, randomized into the following groups: Group 1: AB Serum (ABS); Group 2: Hyaluronic acid (HA); Group 3: Mesenchymal stromal cells (STx.); Group 4: Mesenchymal stromal cells in hyaluronic acid (HA + STx.). After another 4 weeks, the animals were euthanized, followed by histological examination of the removed joints. The histological analysis showed a significant increase in cartilage thickness in the stromal cell treated groups (HA + STx. vs. ABS, p = 0.028; HA + ST.x vs. HA, p = 0.042; STx. vs. ABS, p = 0.036). Scanning electron microscopy detected a similar heterogeneity of mineralization and tissue porosity in the subchondral zone in all groups. The single intra-articular injection of a stem cell containing, GMP-compliant advanced therapy medicinal product for the treatment of iatrogen induced osteoarthritis of the temporomandibular joint shows a chondroregenerative effect.

Recent Biomimetic Approaches for Articular Cartilage Tissue Engineering and Their Clinical Applications: Narrative Review of the Literature

“…In their study, Köhnke et al used an in vivo experiment (rabbit model) to assess the efficacy of adipose-derived mesenchymal stem cells injection for the treatment of temporomandibular joint osteoarthritis in vivo. After a month of follow-up, stem cells, particularly those implanted in hyaluronan, showed the best results in terms of articular cartilage regeneration; nevertheless, there were no statistically significant differences between the four groups when it came to tissue porosity and mineralization heterogeneity [29].…”

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“…Stem cell therapy has also attracted increasing interest from researchers ( Menarim et al, 2019 ; Tang et al, 2021 ). A recent study investigated the ability of intra-articular injection of mesenchymal stromal cells to significantly increase cartilage thickness in an animal model (rabbits) ( Köhnke et al, 2021 ). Mesenchymal stem cell therapy can not only improve the ability of chondrocytes to migrate from healthy to damaged tissues ( Hopper et al, 2015 ), but also secrete cartilage repair-related proteins and trophic factors ( Tang et al, 2021 ), which are essential for cartilage repair.…”

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“…Not surprisingly, the delivered AD-MSCs exhibited protective properties towards chondrocytes, thus preventing cartilage degeneration, and also resulted in milder progression of OA in comparison with the control group [52]. An alternative work by Köhnke et al (2021) involved the evaluation of AD-MSCs injection for the treatment of temporomandibular joint osteoarthritis (TMJ-OA) in vivo using New Zealand white rabbit models. Based on these premises, animal models were randomized to receive one of the following four different injections: (i) AB serum, (ii) HA, (iii) stem cells, or (iv) stem cells loaded in HA.…”

“…Human articular cartilage ECM + AD-MSCs/chondrocytes [27] HA/collagen/fibrinogen + SMSCs + rhTG-4 [28] Human placenta + BM-MSCs ± PRP [30] Alginate spheres + chondrocytes/chondrons [36] 02 Scaffold-Free Strategies Human freeze-dried cancellous bone + human chondrocyte sheets [43] Human chondrocytes ± human synoviocytes [44] hAMSCs cell sheets + cartilage particles [46] 03 Injectables AD-MSCs ± HA [49] Open-porous PLGA microspheres + BM-MSCs [50] MSCs + chondrocytes [51] PEG/ApoPep-1/TCO + chondrocytes [52] E7-Exo + SF-MSCs + KGN [53] 04…”

“…Based on these premises, animal models were randomized to receive one of the following four different injections: (i) AB serum, (ii) HA, (iii) stem cells, or (iv) stem cells loaded in HA. The best outcomes regarding articular cartilage regeneration after a 4-week follow-up were observed with stem cells, especially those embedded in HA; however, there were no significant differences among the four groups in terms of tissue porosity and heterogeneity of mineralization [ 53 ]. A similar injectable was also tested by Qu et al (2021), and the aim was to deliver BM-MSCs using open-porous PLGA microspheres via alkaline treatment, and the results of both in vitro studies and in vivo studies using Sprague–Dawley rat osteochondral defect models confirmed improved articular cartilage regeneration [ 54 ].…”