The Therapeutic Potential of Adipose-Derived Mesenchymal Stem Cell Secretome in Osteoarthritis: A Comprehensive Study.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Mesenchymal Stem Cells*/metabolism ; Osteoarthritis*/metabolism ; Osteoarthritis*/therapy ; Osteoarthritis*/pathology ; Chondrocytes*/metabolism ; Secretome*/metabolism ; Adipose Tissue*/cytology ; Adipose Tissue*/metabolism ; SOX9 Transcription Factor*/metabolism ; SOX9 Transcription Factor*/genetics; Humans ; Core Binding Factor Alpha 1 Subunit/metabolism ; Core Binding Factor Alpha 1 Subunit/genetics ; NF-kappa B/metabolism ; Collagen Type II/metabolism ; Collagen Type II/genetics ; Collagen Type X/metabolism ; Collagen Type X/genetics ; Aggrecans/metabolism ; Aggrecans/genetics ; Cells, Cultured ; Tumor Necrosis Factor-alpha/metabolism

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. This study investigates the therapeutic potential of secretome derived from adipose tissue mesenchymal stem cells (ASCs) in mitigating inflammation and promoting cartilage repair in an in vitro model of OA. Our in vitro model comprised chondrocytes inflamed with TNF. To assess the therapeutic potential of secretome, inflamed chondrocytes were treated with it and concentrations of pro-inflammatory cytokines, metalloproteinases (MMPs) and extracellular matrix markers were measured. In addition, secretome-treated chondrocytes were subject to a microarray analysis to determine which genes were upregulated and which were downregulated. Treating TNF-inflamed chondrocytes with secretome in vitro inhibits the NF - κB pathway, thereby mediating anti-inflammatory and anti-catabolic effects. Additional protective effects of secretome on cartilage are revealed in the inhibition of hypertrophy markers such as RUNX2 and COL10A1, increased production of COL2A1 and ACAN and upregulation of SOX9 . These findings suggest that ASC-derived secretome can effectively reduce inflammation, promote cartilage repair, and maintain chondrocyte phenotype. This study highlights the potential of ASC-derived secretome as a novel, non-cell-based therapeutic approach for OA, offering a promising alternative to current treatments by targeting inflammation and cartilage repair mechanisms.

Arthritis Res Ther. 2023 Jul 3;25(1):113. (PMID: 37400871)
Stem Cell Res. 2019 Jul;38:101463. (PMID: 31108390)
Arthritis Res Ther. 2010;12(5):143. (PMID: 21044355)
EClinicalMedicine. 2020 Nov 26;29-30:100587. (PMID: 34505846)
Arthritis Res Ther. 2013 Jan 08;15(1):R5. (PMID: 23298463)
Arthritis Rheum. 2000 Apr;43(4):801-11. (PMID: 10765924)
Mediators Inflamm. 2014;2014:561459. (PMID: 24876674)
Mediators Inflamm. 2013;2013:357014. (PMID: 24363499)
Stem Cells. 2012 Jan;30(1):42-7. (PMID: 21898694)
Proc Assoc Am Physicians. 1998 Jan-Feb;110(1):65-72. (PMID: 9460084)
Arthritis Res Ther. 2013;15(6):R213. (PMID: 24325988)
J Shoulder Elbow Surg. 2015 Mar;24(3):382-90. (PMID: 25595362)
Biorheology. 2002;39(1-2):237-46. (PMID: 12082286)
Methods Mol Biol. 2012;879:491-504. (PMID: 22610579)
Stem Cell Res Ther. 2021 Oct 30;12(1):561. (PMID: 34717769)
Curr Opin Rheumatol. 2015 Jul;27(4):420-6. (PMID: 26002035)
Biochem Biophys Res Commun. 2002 Apr 26;293(1):501-8. (PMID: 12054629)
Biochim Biophys Acta. 2011 May;1813(5):878-88. (PMID: 21296109)
Eur Cell Mater. 2014 Oct 23;28:269-86. (PMID: 25340806)
Mol Med Today. 1998 Mar;4(3):130-7. (PMID: 9575496)
Nat Genet. 2000 May;25(1):25-9. (PMID: 10802651)
Osteoarthritis Cartilage. 2015 Dec;23(12):2259-2268. (PMID: 26162802)
Bioinformatics. 2004 Dec 12;20(18):3705-6. (PMID: 15297296)
Best Pract Res Clin Rheumatol. 2006 Oct;20(5):983-1002. (PMID: 16980219)
Arthritis Res Ther. 2006;8(4):R124. (PMID: 16859525)
Stem Cells Int. 2014;2014:194318. (PMID: 25548573)
Int J Mol Sci. 2015 Aug 14;16(8):19225-47. (PMID: 26287176)
Nat Med. 2008 Mar;14(3):331-6. (PMID: 18264108)
Arthritis Rheum. 2001 Mar;44(3):585-94. (PMID: 11263773)
J Biol Chem. 2008 Feb 22;283(8):4850-65. (PMID: 18065760)
Genome Biol. 2004;5(10):R80. (PMID: 15461798)
Pathobiology. 2008;75(3):195-9. (PMID: 18550917)
Arthritis Rheum. 2010 Nov;62(11):3365-73. (PMID: 20662062)
Sci Rep. 2015 Jun 09;5:11235. (PMID: 26057572)
Nat Rev Rheumatol. 2010 Apr;6(4):232-41. (PMID: 20177398)
Matrix Biol. 2014 Feb;34:132-43. (PMID: 24140982)
J Bone Metab. 2017 Aug;24(3):147-153. (PMID: 28955690)
Eur Rev Med Pharmacol Sci. 2014;18(23):3580-6. (PMID: 25535126)
Transplantation. 2013 Jun 27;95(12):1535-41. (PMID: 23680930)
Arthritis Rheum. 1998 Jul;41(7):1141-51. (PMID: 9663469)
Int J Mol Sci. 2014 May 15;15(5):8667-98. (PMID: 24837833)
Biomed Res Int. 2014;2014:965849. (PMID: 25530971)
Cytokine Growth Factor Rev. 2019 Apr;46:1-9. (PMID: 30954374)
Bioinformatics. 2008 Jul 1;24(13):1547-8. (PMID: 18467348)
Int J Biochem Cell Biol. 2013 Nov;45(11):2580-4. (PMID: 24004831)
J Clin Med. 2019 Nov 04;8(11):. (PMID: 31689923)
Biochimie. 2013 Dec;95(12):2212-21. (PMID: 23810910)

MCIN/AEI/10.13039/501100011033 (CEX2021-001136-S) MINISTERIO DE CIENCIA E INNOVACIÓN

Keywords: conditioned medium; inflammatory cytokines; mesenchymal stem cells; osteoarthritis; secretome

0 (SOX9 Transcription Factor)
0 (Core Binding Factor Alpha 1 Subunit)
0 (NF-kappa B)
0 (SOX9 protein, human)
0 (Collagen Type II)
0 (ACAN protein, human)
0 (Collagen Type X)
0 (COL10A1 protein, human)
0 (RUNX2 protein, human)
0 (COL2A1 protein, human)
0 (Aggrecans)
0 (Tumor Necrosis Factor-alpha)

Date Created: 20241026 Date Completed: 20241026 Latest Revision: 20241028

20250114

PMC11508730

10.3390/ijms252011287

39457070