Disease-Associated Signatures Persist in Extracellular Vesicles from Reprogrammed Cells of Osteoarthritis Patients.

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-

Extracellular Vesicles*/metabolism ; Osteoarthritis*/metabolism ; Osteoarthritis*/pathology ; Induced Pluripotent Stem Cells*/metabolism ; Induced Pluripotent Stem Cells*/cytology ; Mesenchymal Stem Cells*/metabolism ; Cellular Reprogramming*; Humans ; Cell Differentiation ; Male ; Middle Aged ; Female ; Cells, Cultured

Osteoarthritis (OA) is a prevalent joint disorder that lacks effective therapies to halt cartilage degeneration. Mesenchymal stromal cell (MSC)-derived small extracellular vesicles (sEVs) are being investigated as promising chondroprotective agents. Compared to primary MSCs, induced pluripotent stem cell (iPSC)-derived MSCs (MLCs) offer superior scalability and enhanced paracrine activity. The aim of this study was to explore the feasibility of using autologous MLC-derived sEVs as a potential therapeutic strategy for OA through the analysis of their protein cargo. iPSCs from an OA patient and a healthy donor were differentiated into MLCs. sEVs were isolated from these MLCs and characterized, with a particular focus on their protein cargo. Both iPSC lines were successfully differentiated into MLCs, which secreted sEVs with comparable size distributions and yields. The analysis of differentially expressed proteins revealed a high abundance of proteins associated with OA pathology and cartilage degradation in sEVs from OA MLCs compared to those from healthy MLCs. The persistence of OA-associated protein signatures in autologous MLC-derived sEVs may limit their therapeutic efficacy. These findings underscore the importance of carefully evaluating disease-specific protein profiles in sEVs for regenerative applications.

Stem Cells Int. 2018 Oct 10;2018:9530932. (PMID: 30405725)
Aging (Albany NY). 2020 Jun 9;12(11):10129-10146. (PMID: 32516132)
N Engl J Med. 2021 Jan 7;384(1):51-59. (PMID: 33406330)
Int J Med Sci. 2013 Dec 11;11(1):24-33. (PMID: 24396283)
Int J Mol Sci. 2021 Oct 01;22(19):. (PMID: 34639008)
Cell Death Differ. 2023 May;30(5):1198-1210. (PMID: 36813922)
J Transl Med. 2023 Nov 23;21(1):846. (PMID: 37996918)
BMC Musculoskelet Disord. 2024 Mar 21;25(1):227. (PMID: 38509535)
FEBS Lett. 2015 Apr 13;589(9):1040-7. (PMID: 25728278)
Annu Rev Cell Dev Biol. 2014;30:677-704. (PMID: 25150008)
Front Genet. 2022 Sep 16;13:994163. (PMID: 36186471)
Talanta. 2017 Jul 1;169:170-180. (PMID: 28411808)
Nat Aging. 2021 Apr;1(4):368-384. (PMID: 37117596)
Int J Stem Cells. 2018 May 30;11(1):13-25. (PMID: 29699388)
J Orthop Surg Res. 2023 Nov 8;18(1):849. (PMID: 37941009)
BMC Med Genomics. 2023 Jul 11;16(1):163. (PMID: 37434153)
J Clin Med. 2021 Jul 19;10(14):. (PMID: 34300344)
Sci Rep. 2020 Nov 25;10(1):20560. (PMID: 33239692)
Genet Mol Res. 2013 Mar 13;12(1):738-46. (PMID: 23546957)
J Orthop Res. 2016 Mar;34(3):419-26. (PMID: 26295200)
Sci Rep. 2021 Jun 8;11(1):12023. (PMID: 34103584)
BMC Bioinformatics. 2013 Apr 15;14:128. (PMID: 23586463)
Am J Pathol. 2006 Jan;168(1):131-40. (PMID: 16400016)
J Orthop Surg Res. 2021 Apr 30;16(1):288. (PMID: 33931080)
J Cell Mol Med. 2024 Feb;28(4):e18127. (PMID: 38332532)
J Bone Miner Res. 2020 Jun;35(6):1132-1148. (PMID: 32053224)
Scand J Rheumatol. 2011 Nov;40(6):494-6. (PMID: 22150225)
Pharmaceutics. 2022 May 23;14(5):. (PMID: 35631698)
Aging Dis. 2021 Sep 1;12(6):1409-1422. (PMID: 34527418)
Biochem Biophys Res Commun. 2010 Apr 9;394(3):503-8. (PMID: 20206127)
Inflammation. 2020 Aug;43(4):1498-1509. (PMID: 32248331)
Genes Dis. 2021 Apr 02;9(3):598-609. (PMID: 35782975)
APMIS. 2019 Aug;127(8):588-593. (PMID: 31233243)
Biochemistry (Mosc). 2020 Oct;85(10):1169-1177. (PMID: 33202202)
J Cell Physiol. 2006 Feb;206(2):420-7. (PMID: 16206243)
Cell Rep Med. 2024 May 21;5(5):101574. (PMID: 38776873)
Int J Mol Sci. 2023 Jan 03;24(1):. (PMID: 36614321)
Ageing Res Rev. 2023 Mar;85:101864. (PMID: 36707035)
Eur Rev Med Pharmacol Sci. 2020 May;24(10):5249-5258. (PMID: 32495858)
Nucleic Acids Res. 2023 Jan 6;51(D1):D638-D646. (PMID: 36370105)
J Orthop Surg Res. 2023 Apr 25;18(1):320. (PMID: 37098630)
Open Med (Wars). 2024 Mar 22;19(1):20240902. (PMID: 38584835)
Sci Adv. 2022 Aug 26;8(34):eabn3106. (PMID: 36026443)
Expert Opin Ther Targets. 2009 May;13(5):593-603. (PMID: 19397478)
Cytotherapy. 2008;10(3):243-53. (PMID: 18418770)
Osteoarthritis Cartilage. 2015 Aug;23(8):1233-41. (PMID: 25865392)
Vet J. 2009 Feb;179(2):211-8. (PMID: 17938000)
J Orthop Translat. 2024 Jan 22;44:114-124. (PMID: 38304614)
Arthritis Rheumatol. 2020 Aug;72(8):1266-1277. (PMID: 32162789)
J Invest Dermatol. 2022 May;142(5):1478-1488.e9. (PMID: 34756877)
Acta Biomater. 2021 Jul 1;128:163-174. (PMID: 33862283)
Clin Rheumatol. 2021 Aug;40(8):3247-3256. (PMID: 33420869)
Stem Cell Res Ther. 2017 Mar 9;8(1):64. (PMID: 28279188)
Stem Cell Res. 2020 Mar;43:101683. (PMID: 31962233)
Sci Adv. 2020 Jul 22;6(30):eaba6884. (PMID: 32832666)
Cell Prolif. 2019 Jan;52(1):e12532. (PMID: 30328655)
Aging (Albany NY). 2020 May 12;12(9):8652-8668. (PMID: 32396872)
J Nanobiotechnology. 2024 Apr 12;22(1):177. (PMID: 38609995)
J Mol Biol. 2021 May 28;433(11):166747. (PMID: 33310018)
J Extracell Vesicles. 2021 Nov;10(13):e12160. (PMID: 34724347)
J Extracell Vesicles. 2024 Jul;13(7):e12435. (PMID: 38943211)
Osteoarthritis Cartilage. 2024 Feb;32(2):159-165. (PMID: 38035975)
Joint Bone Spine. 2008 Jul;75(4):439-44. (PMID: 18468937)
Sci Rep. 2023 Oct 18;13(1):17757. (PMID: 37853066)
Clin Immunol. 2023 Dec;257:109812. (PMID: 37866785)
Mol Cancer Ther. 2014 May;13(5):1259-69. (PMID: 24634412)
Healthcare (Basel). 2024 Aug 19;12(16):. (PMID: 39201206)
Front Dent Med. 2022;3:. (PMID: 36685663)
Ann Anat. 2022 Jan;239:151781. (PMID: 34144159)
Int J Biol Macromol. 2017 Jun;99:293-299. (PMID: 28238906)
Osteoarthritis Cartilage. 2001 Oct;9(7):654-63. (PMID: 11597178)
Front Bioeng Biotechnol. 2019 Jan 29;7:9. (PMID: 30761298)
FASEB J. 2023 Jul;37(7):e23011. (PMID: 37249374)
Cells. 2023 Jun 30;12(13):. (PMID: 37443790)
Stem Cells Int. 2021 Oct 9;2021:7232773. (PMID: 34667479)
Osteoarthr Cartil Open. 2023 Dec 04;6(1):100425. (PMID: 38116469)
Polymers (Basel). 2023 Feb 25;15(5):. (PMID: 36904410)
Sci Rep. 2020 Mar 6;10(1):4272. (PMID: 32144293)
Front Cell Dev Biol. 2022 Jul 07;10:910626. (PMID: 35874809)
Cell Death Dis. 2022 Jun 24;13(6):567. (PMID: 35739102)
Anat Cell Biol. 2024 Jun 30;57(2):305-315. (PMID: 38575559)
Cells. 2023 May 18;12(10):. (PMID: 37408255)
Osteoarthr Cartil Open. 2023 Nov 18;5(4):100417. (PMID: 38098679)
Biomater Transl. 2024 Jun 28;5(2):95-113. (PMID: 39351157)
Artif Cells Nanomed Biotechnol. 2024 Dec;52(1):156-174. (PMID: 38423139)
Arthritis Rheum. 2008 May;58(5):1422-32. (PMID: 18438862)

PI20/00933 INSTITUTO DE SALUD CARLOS III; PI17/02197 INSTITUTO DE SALUD CARLOS III; ED431B 2023/58 XUNTA DE GALICIA; ED431B 2020/55 XUNTA DE GALICIA; PROYECTOS DE DESARROLLO Y TRANSFERENCIA 2022 FUNDACIÓN PÚBLICA GALEGA DE INVESTIGACIÓN BIOMÉDICA INIBIC; PROYECTOS DE DESARROLLO Y TRANSFERENCIA 2024 FUNDACIÓN PÚBLICA GALEGA DE INVESTIGACIÓN BIOMÉDICA INIBIC; RSU.UDC.MS06 MINISTERIO DE UNIVERSIDADES; PTA2021-021048-I MINISTERIO DE CIENCIA E INNOVACIÓN

Keywords: autologous cell therapy; cartilage degradation; induced pluripotent stem cells (iPSCs); mesenchymal stromal cells (MSCs); mesenchymal-like cells (MLCs); proteomic analysis; regenerative medicine; small extracellular vesicles (sEVs)

Date Created: 20250213 Date Completed: 20250507 Latest Revision: 20250507

20250508

PMC11816895

10.3390/ijms26030870

39940641