SA1 - Umbilical Cord Stem Cell Lysate: A New Biologic Injection for Treatment of Temporomandibular Joint Inflammation

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Circumference measurements at 48 hours post-induction of inflammation (a), TNF-ɑ activity in the inflamed paw compared to treatments (b), MPO activity in the inflamed paw compared to treatments (c), and cell counts (8-12 µm in diameter) isolated from lavages of the TMJs at the indicated timepoints (d).

Photomicrographs of H&E stains of the peri-articular tissues of the control specimens compared to the 1% cell lysate and the HUCPVC-treated specimens at the 4-hour and 48-hour timepoints. Scale bar = 200 µm. White arrows indicate the anterior (left arrows in photomicrographs) discal attachments and the retrodiscal tissues (right arrows in photomicrographs) where increases in cell density in the synovial lining were observed in the controls and not the treated specimens.

Photomicrographs of H&E stains of the anterior discal attachments and synovial lining of the control specimens compared to the 1% cell lysate and the HUCPVC-treated specimens at the 4-hour and 48-hour timepoints. The white arrow in the top left photomicrograph demonstrates a region of capillaries that were dispersed throughout the underlying loose connective tissue below the synovial lining in the 4-hour control. The 48-hour control specimen demonstrates increased cell density (white arrow) in the synovial lining and the formation of villous-like projections secondary to infolding of the synovial lining that was not observed in the lysate and HUCPVC-treated specimens. Scale bar = 200 µm for 1% cell lysate and HUCPVC-treated groups, 100 µm for control.

Oral Abstract Presenter(s)

Christopher K. Ward, DMD, BSc

Oral and Maxillofacial Surgery Resident
University of Toronto
Toronto, Ontario, Canada

Disclosure: Nothing to disclose.

Co-Author(s)

RG

Rita G. Gill, B.Sc, MASc

Research Technician, Princess Margaret Cancer Research Tower
University of Toronto
Mississauga, Ontario, Canada

Disclosure: Nothing to disclose.
John E. Davies, B.Sc., B.D.S., Ph.D., D.Sc., F.S.B.E.

Professor & Associate Director, Graduate Programs, Institute for Biomedical Engineering (BME)
University of Toronto
Toronto, Ontario, Canada

Disclosure: Tissue Regeneration Therapeutics Inc. (Other Research Support includes receipt of drugs, supplies, equipment or other in-kind support, Ownership Interest includes stock, stock options, patent or other intellectual property, Research Grant includes principal investigator, collaborator or consultant and pending grants as well as grants already received)

Abstract:

Purpose:
Progressive degenerative diseases that affect the TMJ, such as osteoarthritis (OA), juvenile idiopathic arthritis (JIA), and idiopathic condylar resorption (ICR), are characterized by ongoing loss of articular fibrocartilage, subchondral bone remodeling, and synovitis.1 These structures can be preserved by reducing inflammation and thereby slowing the progressive catabolic cellular processes underlying the pathogenesis of these conditions.1 Given that mesenchymal stem cells and their derivatives have now been employed in the treatment of numerous systemic pro-inflammatory conditions with promising outcomes, the goal of this study was to investigate the anti-inflammatory effects of human umbilical cord perivascular mesenchymal cells (HUCPVCS) and a cell lysate (CL) derived therefrom in an established hind-paw model of carrageenan-induced inflammation, then further evaluate their anti-inflammatory potential in a model of temporomandibular joint inflammation.2

Methods:
Female CD1 mice (n = 8 per group) underwent hind-paw injections of carrageenan for induction of inflammation, followed by treatment with saline (control), 1% CL, or HUCPVCS. Tissue edema was assessed by measuring paw circumference prior to injections and 48 hours later. Hind paws were excised post-sacrifice to assess MPO and TNF-alpha concentrations. Male Wistar rats (n = 8 per group) underwent intra-articular TMJ injections of either saline followed by carrageenan (control), 1% CL, or viable HUCPVCS. Rats were sacrificed at 4 and 48 hours post-injection. Articular tissue as well as synovial aspirates were obtained for histologic analysis and to assess leukocyte infiltration. The effects of CL and HUCPVCS on TNF-alpha and MPO concentrations were analyzed using 1-way ANOVA and post-hoc Tukey tests for pairwise comparisons between means of groups, while linear regression modeling was utilized to assess differences in leukocyte infiltration.

Results:
For the results, 1% CL and HUCPVC-treated hind paws demonstrated a reduction tissue edema and significantly lower concentrations of MPO and TNF-alpha 48 hours post-injection compared to controls. Treated TMJs demonstrated lower concentrations of leukocytes in the synovium post-Injection compared to controls. Histologic analysis of the TMJs from treatment groups demonstrated a reduction in signs of acute inflammation when compared to controls.

Conclusion: HUCPVCs and their CL derivatives reduced tissue edema, levels of pro-inflammatory mediators, leukocyte infiltration, while modulating signs of TMJ inflammation histologically.

References:
1. Wang XD, Zhang JN, Gan YH, et al: Current understanding of pathogenesis and treatment of TMJ osteoarthritis. J Dent Res 94:5, 2015

2. Weiss DJ, English K, Krasnodembskaya A, et al: The necrobiology of mesenchymal stromal cells affects therapeutic efficacy. Front Immunol. 10:1228, 2019