Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Research Article

A Single Dose of Local Injection of Adipose Stem Cells Promotes Ectopic Cartilage Regeneration In Vivo by Modulating Inflammatory Response and Enhancing Cartilage Extracellular Matrix Synthesis in a Porcine Model

Author(s): Tianyu Huang, Hengyun Sun*, Jianguo Chen, Xia Liu, Bo Pan, Leren He and Haiyue Jiang*

Volume 18, Issue 2, 2023

Published on: 11 August, 2022

Page: [237 - 246] Pages: 10

DOI: 10.2174/1574888X17666220425122317

Price: $65

Abstract

Background: Uncontrollable inflammatory response following ectopic engineered cartilage implantation is devastating to the aesthetic and functional outcomes of the recipients. Adipose stem cells (ASCs) have a good immunomodulatory capacity via a paracrine mechanism. However, works of literature are scarce regarding ASC modulation in ectopic engineered cartilage regeneration in vivo. This study aims to explore how ASCs modulate the inflammatory response after engineered cartilage implantation and affect the implants in a nonchondrogenic milieu in large immunocompetent animals.

Methods: Porcine engineered elastic cartilages were cultured in vitro for 3 weeks with chondrocyte cell sheeting technology and then assigned into two groups: ASCs and Control (saline injection). All samples (n= 6 per group) were autologously implanted into different subcutaneous pockets, and a single dose of ASCs was injected at three points around the implant. All samples were harvested after 2 weeks in vivo for analysis.

Results: In the examination of inflammation, we observed reduced inflammatory cell infiltration and improved M2 macrophage polarization in the implanted engineered cartilage with ASC injection compared to the control. There were also enhanced anti-inflammatory cytokines and reduced proinflammatory cytokines inside and adjacent to the implants, while in serum, there were no significant differences. In the examination of the cartilage quality, there were significant increases in cartilage extracellular matrix and chondrogenic factors, and the elastic cartilage phenotype was maintained compared to control.

Conclusion: This study finds that a single dose of ASCs can promote ectopic cartilage regeneration by modulating inflammation and enhancing cartilage matrix synthesis in a porcine model.

Keywords: Adipose stem cells, cartilage tissue engineering, inflammatory modulation, chondrogenesis, porcine model.

Graphical Abstract

[1]
Lynn AK, Brooks RA, Bonfield W, Rushton N. Repair of defects in articular joints. Prospects for material-based solutions in tissue engineering. J Bone Joint Surg Br 2004; 86(8): 1093-9.
[http://dx.doi.org/10.1302/0301-620X.86B8.15609] [PMID: 15568518]
[2]
Kwon H, Brown WE, Lee CA, et al. Surgical and tissue engineering strategies for articular cartilage and meniscus repair. Nat Rev Rheumatol 2019; 15(9): 550-70.
[http://dx.doi.org/10.1038/s41584-019-0255-1] [PMID: 31296933]
[3]
Makris EA, Gomoll AH, Malizos KN, Hu JC, Athanasiou KA. Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol 2015; 11(1): 21-34.
[http://dx.doi.org/10.1038/nrrheum.2014.157] [PMID: 25247412]
[4]
Zhou G, Jiang H, Yin Z, et al. In vitro Regeneration of Patient-specific Ear-shaped Cartilage and Its First Clinical Application for Auricular Reconstruction. In vitro regeneration of patient-specific ear-shaped cartilage and its first clinical application for auricular reconstruction. EBioMedicine 2018; 28: 287-302.
[http://dx.doi.org/10.1016/j.ebiom.2018.01.011] [PMID: 29396297]
[5]
Ding J, Chen B, Lv T, et al. Bone marrow mesenchymal stem cell-based engineered cartilage ameliorates polyglycolic acid/polylactic acid scaffold-induced inflammation through m2 polarization of macrophages in a pig model. Stem Cells Transl Med 2016; 5(8): 1079-89.
[http://dx.doi.org/10.5966/sctm.2015-0263] [PMID: 27280797]
[6]
Kanazawa S, Fujihara Y, Sakamoto T, et al. Tissue responses against tissue-engineered cartilage consisting of chondrocytes encapsulated within non-absorbable hydrogel. J Tissue Eng Regen Med 2013; 7(1): 1-9.
[http://dx.doi.org/10.1002/term.458] [PMID: 21916014]
[7]
Chambers ES, Vukmanovic-Stejic M. Skin barrier immunity and ageing. Immunology 2020; 160(2): 116-25.
[http://dx.doi.org/10.1111/imm.13152] [PMID: 31709535]
[8]
Fahy N, Farrell E, Ritter T, Ryan AE, Murphy JM. Immune modulation to improve tissue engineering outcomes for cartilage repair in the osteoarthritic joint. Tissue Eng Part B Rev 2015; 21(1): 55-66.
[http://dx.doi.org/10.1089/ten.teb.2014.0098] [PMID: 24950588]
[9]
Li X, Ellman M, Muddasani P, et al. Prostaglandin E2 and its cognate EP receptors control human adult articular cartilage homeostasis and are linked to the pathophysiology of osteoarthritis. Arthritis Rheum 2009; 60(2): 513-23.
[http://dx.doi.org/10.1002/art.24258] [PMID: 19180509]
[10]
Ohashi H, Nishida K, Yoshida A, et al. Adipose-derived extract suppresses il-1β-induced inflammatory signaling pathways in human chondrocytes and ameliorates the cartilage destruction of experimental osteoarthritis in rats. Int J Mol Sci 2021; 22(18): 9781.
[http://dx.doi.org/10.3390/ijms22189781] [PMID: 34575945]
[11]
Djouad F, Rackwitz L, Song Y, Janjanin S, Tuan RS. ERK1/2 activation induced by inflammatory cytokines compromises effective host tissue integration of engineered cartilage. Tissue Eng Part A 2009; 15(10): 2825-35.
[http://dx.doi.org/10.1089/ten.tea.2008.0663] [PMID: 19243242]
[12]
Varol C, Mildner A, Jung S. Macrophages: Development and tissue specialization. Annu Rev Immunol 2015; 33(1): 643-75.
[http://dx.doi.org/10.1146/annurev-immunol-032414-112220] [PMID: 25861979]
[13]
Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 2008; 16(2): 137-62.
[http://dx.doi.org/10.1016/j.joca.2007.12.013] [PMID: 18279766]
[14]
Kikuchi S, Togo K, Ebata N, et al. A retrospective database study of gastrointestinal events and medical costs associated with nonsteroidal anti-inflammatory drugs in japanese patients of working age with osteoarthritis and chronic low back pain. Pain Med 2021; 22(5): 1029-38.
[http://dx.doi.org/10.1093/pm/pnaa421] [PMID: 33585939]
[15]
Fidahic M, Jelicic Kadic A, Radic M, Puljak L. Celecoxib for rheumatoid arthritis. Cochrane Database Syst Rev 2017; 6: CD012095.
[PMID: 28597983]
[16]
Desando G, Cavallo C, Sartoni F, et al. Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model. Arthritis Res Ther 2013; 15(1): R22.
[http://dx.doi.org/10.1186/ar4156] [PMID: 23360790]
[17]
ter Huurne M, Schelbergen R, Blattes R, et al. Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum 2012; 64(11): 3604-13.
[http://dx.doi.org/10.1002/art.34626] [PMID: 22961401]
[18]
Zhang P, Liu Y, Jia L, et al. SP600125, a JNK-Specific Inhibitor, Regulates in vitro auricular cartilage regeneration by promoting cell pro-liferation and inhibiting extracellular matrix metabolism. Front Cell Dev Biol 2021; 9: 630678.
[http://dx.doi.org/10.3389/fcell.2021.630678] [PMID: 33816478]
[19]
Yoshida K, Nakashima A, Doi S, et al. Serum-free medium enhances the immunosuppressive and antifibrotic abilities of mesenchymal stem cells utilized in experimental renal fibrosis. Stem Cells Transl Med 2018; 7(12): 893-905.
[http://dx.doi.org/10.1002/sctm.17-0284] [PMID: 30269426]
[20]
Beerts C, Brondeel C, Pauwelyn G, et al. Scintigraphic tracking of 99mTechnetium-labelled equine peripheral blood-derived mesenchymal stem cells after intravenous, intramuscular, and subcutaneous injection in healthy dogs. Stem Cell Res Ther 2021; 12(1): 393.
[http://dx.doi.org/10.1186/s13287-021-02457-9] [PMID: 34256833]
[21]
Abdelgawad M, Bakry NS, Farghali AA, Abdel-Latif A, Lotfy A. Mesenchymal stem cell-based therapy and exosomes in COVID-19: current trends and prospects. Stem Cell Res Ther 2021; 12(1): 469.
[http://dx.doi.org/10.1186/s13287-021-02542-z] [PMID: 34419143]
[22]
Fernandes TL, Gomoll AH, Lattermann C, Hernandez AJ, Bueno DF, Amano MT. Macrophage: A Potential target on cartilage regeneration. Front Immunol 2020; 11: 111.
[http://dx.doi.org/10.3389/fimmu.2020.00111] [PMID: 32117263]
[23]
Zhang H, Cai D, Bai X. Macrophages regulate the progression of osteoarthritis. Osteoarthritis Cartilage 2020; 28(5): 555-61.
[http://dx.doi.org/10.1016/j.joca.2020.01.007] [PMID: 31982565]
[24]
Harrell CR, Markovic BS, Fellabaum C, Arsenijevic A, Volarevic V. Mesenchymal stem cell-based therapy of osteoarthritis: Current knowledge and future perspectives. Biomed Pharmacother 2019; 109: 2318-26.
[http://dx.doi.org/10.1016/j.biopha.2018.11.099] [PMID: 30551490]
[25]
Behrendt P, Feldheim M, Preusse-Prange A, et al. Chondrogenic potential of IL-10 in mechanically injured cartilage and cellularized collagen ACI grafts. Osteoarthritis Cartilage 2018; 26(2): 264-75.
[http://dx.doi.org/10.1016/j.joca.2017.11.007] [PMID: 29169959]
[26]
Galéra P, Rédini F, Vivien D, et al. Effect of transforming growth factor-beta 1 (TGF-beta 1) on matrix synthesis by monolayer cultures of rabbit articular chondrocytes during the dedifferentiation process. Exp Cell Res 1992; 200(2): 379-92.
[http://dx.doi.org/10.1016/0014-4827(92)90186-C] [PMID: 1572404]
[27]
Redini F, Galera P, Mauviel A, Loyau G, Pujol JP. Transforming growth factor beta stimulates collagen and glycosaminoglycan biosynthesis in cultured rabbit articular chondrocytes. FEBS Lett 1988; 234(1): 172-6.
[http://dx.doi.org/10.1016/0014-5793(88)81327-9] [PMID: 3164687]
[28]
Pujol JP, Chadjichristos C, Legendre F, et al. Interleukin-1 and transforming growth factor-beta 1 as crucial factors in osteoarthritic cartilage metabolism. Connect Tissue Res 2008; 49(3): 293-7.
[http://dx.doi.org/10.1080/03008200802148355] [PMID: 18661363]
[29]
Krishnan Y, Grodzinsky AJ. Cartilage diseases. Matrix Biol 2018; 71-72: 51-69.
[http://dx.doi.org/10.1016/j.matbio.2018.05.005] [PMID: 29803938]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy