Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Oral Health
Published in: BMC Oral Health 1/2023

Open Access 01-12-2023 | Arthritis | Research

Photobiostimulation conjugated with stem cells or their secretome for temporomandibular joint arthritis in a rat model

Authors: Rana El-Qashty, Osama A. Elkashty, Eman Hany

Published in: BMC Oral Health | Issue 1/2023

Login to get access

Abstract

Background

Temporomandibular joint (TMJ) arthritis is a debilitating, challenging condition and different methods have been implicated for its treatment. This study aimed to test the therapeutic potentials of low-level laser therapy (LLLT) associated with adipose derived stem cells (ADSC) or their derived secretome on a murine model induced arthritis.

Methods

Forty eight rats were divided into four groups where group I was the sham control, the rest of animals were subjected to arthritis induction using complete Freund’s adjuvant, then divided as follows: group II received phosphate buffered saline (PBS) intraarticular injection and irradiation of 0 j/cm2, group III received ADSCs derived secretome and irradiation of 38 j/cm2, and group IV received ADSCs and irradiation of 38 j/cm2 as well. One and three weeks after treatment, animals were euthanized, and paraffin blocks were processed for histological assessment by hematoxylin and eosin stain with histomorphometrical analysis. Histochemical evaluation of joint proteoglycan content was performed through toluidine blue stain, and immunohistochemical staining by the proinflammatory marker tumor necrosis factor-α (TNF-α) was performed followed by the relevant statistical tests.

Results

The arthritis group showed histological signs of joint injury including cartilage atrophy, articular disc fibrosis, irregular osteochondral interface, and condylar bone resorption together with high inflammatory reaction and defective proteoglycan content. In contrast, the treated groups III and IV showed much restoration of the joint structure with normal cartilage and disc thickness. The inflammation process was significantly suppressed especially after three weeks as confirmed by the significant reduction in TNF-α positive immunostaining compared to the arthritic group, and the cartilage proteoglycan content also showed significant increase relative to the arthritic group. However, no significant difference between the results of the two treated groups was detected.

Conclusion

LLLT conjugated with ADSCs or ADSCs derived secretome can efficiently enhance the healing of arthritic TMJs. Stem cell secretome can be applied as a safe, potent therapy. However, further investigations are required to unravel its mechanism of action and pave its way as a safe, novel, cell free therapy.

Graphical Abstract

Literature
1.
Chang C-L, Wang D-H, Yang M-C, Hsu W-E, Hsu M-L. Functional disorders of the temporomandibular joints: Internal derangement of the temporomandibular joint. Kaohsiung J Med Sci. 2018;34(4):223–30.PubMed
2.
Wilkie G, Al-Ani Z. Temporomandibular joint anatomy, function and clinical relevance. Br Dent J. 2022;233(7):539–46.PubMed
3.
Stoll ML, Kau CH, Waite PD, Cron RQ. Temporomandibular joint arthritis in juvenile idiopathic arthritis, now what? Pediatr Rheumatol. 2018;16(1):32.
4.
Aldelaimi T, Aldelaimi A, Enezei H, Faisal R. Gummy smile esthetic correction with 940 nm Diode Laser. Int Med J. 1994;2019(26):513–5.
5.
Aldelaimi TN, Khalil AA. Clinical application of diode laser (980 nm) in maxillofacial surgical procedures. J Craniofac Surg. 2015;26(4):1220–3.PubMed
6.
Alshamaa A, Aldelaimi T. Treatment of myogenic temporomandibular joint disorders with diode laser and pharmacotherapy (comparative study). Int Med J. 1994;2020(25):461.
7.
Lemos GA, Rissi R, de Souza Pires IL, de Oliveira LP, de Aro AA, Pimentel ER, et al. Low-level laser therapy stimulates tissue repair and reduces the extracellular matrix degradation in rats with induced arthritis in the temporomandibular joint. Lasers Med Sci. 2016;31(6):1051–9.PubMed
8.
Carlos FP, da Silva MdPA, Melo EdLVS, Costa MS, Zamuner SR. Protective effect of low-level laser therapy (LLLT) on acute zymosan-induced arthritis. Lasers Med Sci. 2014;29(2):757–63.PubMed
9.
Zhang S, Yap AU, Toh WS. Stem cells for temporomandibular joint repair and regeneration. Stem Cell Rev Rep. 2015;11(5):728–42.PubMed
10.
El Qashty RM, Mohamed NN, Radwan LR, Ibrahim FM. Effect of bone marrow mesenchymal stem cells on healing of temporomandibular joints in rats with induced rheumatoid arthritis. Eur J Oral Sci. 2018;126(4):272–81.PubMed
11.
Kehoe O, Cartwright A, Askari A, El Haj AJ, Middleton J. Intra-articular injection of mesenchymal stem cells leads to reduced inflammation and cartilage damage in murine antigen-induced arthritis. J Transl Med. 2014;12(1):157.PubMedPubMedCentral
12.
Baer PC, Geiger H. Adipose-derived mesenchymal stromal/stem cells: tissue localization, characterization, and heterogeneity. Stem Cells Int. 2012;2012:812693.PubMedPubMedCentral
13.
Keyhanmanesh R, Khodamoradi F, Rahbarghazi R, Rahbarghazi A, Rezaie J, Ahmadi M, et al. Intra-tracheal delivery of mesenchymal stem cell-conditioned medium ameliorates pathological changes by inhibiting apoptosis in asthmatic rats. Mol Biol Rep. 2022;49(5):3721–8.PubMed
14.
Shrivastava AK, Singh HV, Raizada A, Singh SK, Pandey A, Singh N, et al. Inflammatory markers in patients with rheumatoid arthritis. Allergol Immunopathol (Madr). 2015;43(1):81–7.PubMed
15.
Inam Illahi M, Amjad S, Alam SM, Ahmed ST, Fatima M, Shahid MA. Serum tumor necrosis factor-alpha as a competent biomarker for evaluation of disease activity in early rheumatoid arthritis. Cureus. 2021;13(5):e15314.PubMedPubMedCentral
16.
El-Qashty R, Elkashty OA, Hany E. Therapeutic potential of low-level laser photobiomodulation on adjuvant induced temporomandibular joint arthritis in a rat model. Mansoura J Dent. 2023;10(1):1–8.
17.
AbouElkhier M, Mohamed N, Mourad M. Therapeutic potential of intra-articular injection of bone marrow mesenchymal stem cells on tempromandibular joints’ induced osteoarthritis. An experimental study. Dent Oral Biol. 2018;3:1150.
18.
Hany E, Yahia S, Elsherbeny MF, Salama NM, Ateia IM, Abou El-Khier NT, et al. Evaluation of the osteogenic potential of rat adipose-derived stem cells with different polycaprolactone/alginate-based nanofibrous scaffolds: an in vitro study. Stem Cell Investig. 2020;7:14.PubMedPubMedCentral
19.
Yang C, Lei D, Ouyang W, Ren J, Li H, Hu J, et al. Conditioned media from human adipose tissue-derived mesenchymal stem cells and umbilical cord-derived mesenchymal stem cells efficiently induced the apoptosis and differentiation in human glioma cell lines in vitro. BioMed Res Int. 2014;2014:109389.
20.
Grässel S, Muschter D. Recent advances in the treatment of osteoarthritis. F1000Res. 2020;9:F1000 Faculty Rev-325.
21.
Zaringhalam J, Akhtari Z, Eidi A, Ruhani AH, Tekieh E. Relationship between serum IL10 level and p38MAPK enzyme activity on behavioral and cellular aspects of variation of hyperalgesia during different stages of arthritis in rats. Inflammopharmacology. 2014;22(1):37–44.PubMed
22.
Lemos GA, Batista AUD, da Silva PLP, Araújo DN, Sarmento WEA, Palomari ET. Photobiostimulation activity of different low-level laser dosage on masticatory muscles and temporomandibular joint in an induced arthritis rat model. Lasers Med Sci. 2020;35(5):1129–39.PubMed
23.
Peimani A, Sardary F. Effect of low-level laser on healing of temporomandibular joint osteoarthritis in rats. J Dent. 2014;11(3):319–27.
24.
Adães S, Mendonça M, Santos TN, Castro-Lopes JM, Ferreira-Gomes J, Neto FL. Intra-articular injection of collagenase in the knee of rats as an alternative model to study nociception associated with osteoarthritis. Arthritis Res Ther. 2014;16(1):R10.PubMedPubMedCentral
25.
Kalladka M, Quek S, Heir G, Eliav E, Mupparapu M, Viswanath A. Temporomandibular joint osteoarthritis: diagnosis and long-term conservative management: a topic review. J Indian Prosthodont Soc. 2014;14(1):6–15.PubMed
26.
Ishizuka Y, Shibukawa Y, Nagayama M, Decker R, Kinumatsu T, Saito A, et al. TMJ degeneration in SAMP8 mice is accompanied by deranged Ihh signaling. J Dent Res. 2014;93(3):281–7.PubMedPubMedCentral
27.
Salgado AJ, Reis RL, Sousa NJ, Gimble JM. Adipose tissue derived stem cells secretome: soluble factors and their roles in regenerative medicine. Curr Stem Cell Res Ther. 2010;5(2):103–10.PubMed
28.
Zheng G, Huang R, Qiu G, Ge M, Wang J, Shu Q, et al. Mesenchymal stromal cell-derived extracellular vesicles: regenerative and immunomodulatory effects and potential applications in sepsis. Cell Tissue Res. 2018;374(1):1–15.PubMed
29.
Cheng JH, Hsu CC, Hsu SL, Chou WY, Wu YN, Kuo CA, et al. Adipose-derived mesenchymal stem cells-conditioned medium modulates the expression of inflammation induced bone morphogenetic protein-2, -5 and -6 as well as compared with shockwave therapy on rat knee osteoarthritis. Biomedicines. 2021;9(10):1399.PubMedPubMedCentral
30.
Nazemian V, Manaheji H, Sharifi AM, Zaringhalam J. Long term treatment by mesenchymal stem cells conditioned medium modulates cellular, molecular and behavioral aspects of adjuvant-induced arthritis. Cell Mol Biol (Noisy-le-grand). 2018;64(1):19–26.PubMed
31.
Yew T-L, Hung Y-T, Li H-Y, Chen H-W, Chen L-L, Tsai K-S, et al. Enhancement of wound healing by human multipotent stromal cell conditioned medium: the paracrine factors and p38 MAPK activation. Cell Transplant. 2011;20(5):693–706.PubMed
32.
Chen W, Sun Y, Gu X, Hao Y, Liu X, Lin J, et al. Conditioned medium of mesenchymal stem cells delays osteoarthritis progression in a rat model by protecting subchondral bone, maintaining matrix homeostasis, and enhancing autophagy. J Tissue Eng Regen Med. 2019;13(9):1618–28.PubMed
33.
Soetjahjo B, Hidayat M, Sujuti H, Fibrianto YH. The significant effect of conditioned medium of umbilical cord mesenchymal stem cells in histological improvement of cartilage defect in wistar rats. Turkish J Immunol. 2018;6(2):n. pag.
34.
Cosenza S, Ruiz M, Toupet K, Jorgensen C, Noël D. Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis. Sci Rep. 2017;7(1):16214.PubMedPubMedCentral
35.
Zhang S, Chuah SJ, Lai RC, Hui JHP, Lim SK, Toh WS. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity. Biomaterials. 2018;156:16–27.PubMed
36.
Khatab S, van Osch GJ, Kops N, Bastiaansen-Jenniskens YM, Bos PK, Verhaar JA, et al. Mesenchymal stem cell secretome reduces pain and prevents cartilage damage in a murine osteoarthritis model. Eur Cell Mater. 2018;36:218–30.PubMed
37.
Molnar V, Pavelić E, Vrdoljak K, Čemerin M, Klarić E, Matišić V, et al. Mesenchymal stem cell mechanisms of action and clinical effects in osteoarthritis: a narrative review. Genes. 2022;13(6):949.PubMedPubMedCentral
38.
Yan B, Lv S, Tong P, Yan L, Chen Z, Zhou L, et al. Intra-articular injection of adipose-derived stem cells ameliorates pain and cartilage anabolism/catabolism in osteoarthritis: preclinical and clinical evidences. Front Pharmacol. 2022;13:854025.PubMedPubMedCentral
39.
Khairy M, Abulmagd I, Sabry D. Evaluation of the therapeutic potentials of adipose derived stem cells in comparison to hyaluronic acid in temporomandibular joint osteoarthritis A multi assessment study. Egypt J Oral Maxillofac Surg. 2019;10(4):102–17.
40.
Farivar S, Malekshahabi T, Shiari R. Biological effects of low level laser therapy. J Lasers Med Sci. 2014;5(2):58–62.PubMedPubMedCentral
41.
Schneider C, Dungel P, Priglinger E, Danzer M, Schädl B, Nürnberger S. The impact of photobiomodulation on the chondrogenic potential of adipose-derived stromal/stem cells. J Photochem Photobiol B. 2021;221:112243.PubMed
42.
Stancker TG, Vieira SS, Serra AJ, do Nascimento Lima R, Dos Santos Feliciano R, Silva JA Jr, et al. Can photobiomodulation associated with implantation of mesenchymal adipose-derived stem cells attenuate the expression of MMPs and decrease degradation of type II collagen in an experimental model of osteoarthritis? Lasers Med Sci. 2018;33(5):1073–84.PubMed
43.
Fekrazad R, Eslaminejad MB, Shayan AM, Kalhori KA, Abbas FM, Taghiyar L, et al. Effects of photobiomodulation and mesenchymal stem cells on articular cartilage defects in a rabbit model. Photomed Laser Surg. 2016;34(11):543–9.PubMed
44.
Asgari M, Gazor R, Abdollahifar M-A, Fadaei Fathabady F, Zare F, Norouzian M, et al. Combined therapy of adipose-derived stem cells and photobiomodulation on accelerated bone healing of a critical size defect in an osteoporotic rat model. Biochem Biophys Res Commun. 2020;530(1):173–80.PubMed
45.
Wang YH, Wu JY, Kong SC, Chiang MH, Ho ML, Yeh ML, et al. Low power laser irradiation and human adipose-derived stem cell treatments promote bone regeneration in critical-sized calvarial defects in rats. PLoS One. 2018;13(4):e0195337.PubMedPubMedCentral
46.
Memis S, Candirli C, Kerimoglu G. Short term histopathological effects of GaAlAs laser on experimentally induced TMJ osteoarthritis in rabbits. Braz Oral Res. 2018;32:e90.PubMed
47.
da Cunha LA, Firoozmand LM, da Silva AP, Camargo SE, Oliveira W. Efficacy of low-level laser therapy in the treatment of temporomandibular disorder. Int Dent J. 2008;58(4):213–7.PubMed
48.
Zhang S, Jiang YZ, Zhang W, Chen L, Tong T, Liu W, et al. Neonatal desensitization supports long-term survival and functional integration of human embryonic stem cell-derived mesenchymal stem cells in rat joint cartilage without immunosuppression. Stem Cells Dev. 2013;22(1):90–101.PubMed
49.
Nori S, Okada Y, Nishimura S, Sasaki T, Itakura G, Kobayashi Y, et al. Long-term safety issues of iPSC-based cell therapy in a spinal cord injury model: oncogenic transformation with epithelial-mesenchymal transition. Stem Cell Rep. 2015;4(3):360–73.
50.
Conforti A, Scarsella M, Starc N, Giorda E, Biagini S, Proia A, et al. Microvescicles derived from mesenchymal stromal cells are not as effective as their cellular counterpart in the ability to modulate immune responses in vitro. Stem Cells Dev. 2014;23(21):2591–9.PubMedPubMedCentral
51.
Carvalho CM, Lacerda JA, dos Santos Neto FP, de Castro ICV, Ramos TA, de Lima FO, et al. Evaluation of laser phototherapy in the inflammatory process of the rat’s TMJ induced by carrageenan. Photomed Laser Surg. 2011;29(4):245–54.PubMed
52.
Pires D, Xavier M, Araújo T, Silva JA Jr, Aimbire F, Albertini R. Low-level laser therapy (LLLT; 780 nm) acts differently on mRNA expression of anti- and pro-inflammatory mediators in an experimental model of collagenase-induced tendinitis in rat. Lasers Med Sci. 2011;26(1):85–94.PubMed
53.
Hany E, Elkashty AAR, El-Qashty R. The regenerative potential of adipose-derived stem cells versus their conditioned media on tongue defects of adult male rats. Egypt J Histol. 2022.
54.
Rani S, Ryan AE, Griffin MD, Ritter T. Mesenchymal stem cell-derived extracellular vesicles: toward cell-free therapeutic applications. Mol Ther. 2015;23(5):812–23.PubMedPubMedCentral
55.
Korb-Pap A, Stratis A, Mühlenberg K, Niederreiter B, Hayer S, Echtermeyer F, et al. Early structural changes in cartilage and bone are required for the attachment and invasion of inflamed synovial tissue during destructive inflammatory arthritis. Ann Rheum Dis. 2012;71(6):1004–11.PubMed
56.
Ogasawara N, Kano F, Hashimoto N, Mori H, Liu Y, Xia L, et al. Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental temporomandibular joint osteoarthritis. Osteoarthritis Cartilage. 2020;28(6):831–41.PubMed
57.
Kay AG, Long G, Tyler G, Stefan A, Broadfoot SJ, Piccinini AM, et al. Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis. Sci Rep. 2017;7(1):18019.PubMedPubMedCentral
58.
Gabr H, Helal O, Mohamed H, Abo Elkheir W, El-Bedawy S, Abo Elkheir A. Comparison between mesenchymal stem cells, stem cell conditioned media, and mesenchymal stem cell derived microsvesicles in regeneration in murine model of acute renal injury. Cytotherapy. 2017;19(5, Supplement):S25.
59.
Abdel Aal S, Abdelrahman S, Raafat N. Comparative therapeutic effects of mesenchymal stem cells versus their conditioned media in alleviation of CCL4-induced liver fibrosis in rats : histological and biochemical study. J Med Histol. 2019;3(1):1–20.
60.
Foo JB, Looi QH, Chong PP, Hassan NH, Yeo GEC, Ng CY, et al. Comparing the therapeutic potential of stem cells and their secretory products in regenerative medicine. Stem Cells Int. 2021;2021:2616807.PubMedPubMedCentral
61.
Rosochowicz MA, Lach MS, Richter M, Suchorska WM, Trzeciak T. Conditioned medium - is it an undervalued lab waste with the potential for osteoarthritis management? Stem Cell Rev Rep. 2023;19(5):1185–213.PubMedPubMedCentral
62.
Alderman TS, Carpenter CB, McGirr RJAB. Animal research biosafety. Appl Biosaf. 2018;23(3):130–42.
Metadata
Title
Photobiostimulation conjugated with stem cells or their secretome for temporomandibular joint arthritis in a rat model
Authors
Rana El-Qashty
Osama A. Elkashty
Eman Hany
Publication date
01-12-2023
Publisher
BioMed Central
Keyword
Arthritis
Published in
BMC Oral Health / Issue 1/2023
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-023-03466-1

Other articles of this Issue 1/2023

BMC Oral Health 1/2023 Go to the issue

Research

Effect of continuous chelation on the dentinal tubule penetration of a calcium silicate–based root canal sealer: a confocal laser microscopy study

Research

Morphometric analysis of tooth morphology among different malocclusion groups in a hispanic population

Research

Factors predicting different times for brushing teeth during the day: multilevel analyses

Research

The effect of using denture adhesives on patient satisfaction with complete dentures; a randomized clinical trial

Research

MDP-salts as an adhesion promoter with MDP-primers and self-adhesive resin cement for zirconia cementation

Research

The mechanical and clinical influences of prosthetic index structure in Morse taper implant-abutment connection: a scoping review