The Effect of Human Bone Marrow Mesenchymal Stem Cell-Derived Exosomes on Cartilage Repair in Rabbits

Overview

Journal Stem Cells Int

Publisher Wiley

Specialty Cell Biology

Date 2022 Sep 19

PMID 36117721

Authors

Hongwei Yang

Meng Cong

Weixiao Huang

Jin Chen

Min Zhang

Xiaosong Gu

Cheng Sun

Huilin Yang

Affiliations

Soon will be listed here.

Abstract

Mesenchymal stem cells (MSCs) have shown chondroprotective effects in cartilage repair. However, side effects caused by MSC treatment limit their application in clinic. As a cell-free therapy, MSC-derived exosomes (EXOs) have attracted much more attention in recent years. In the present study, we prepared EXOs from human bone marrow mesenchymal stem cells (hBMSCs) and examined their therapeutic potentials in cartilage repair. Our results showed that the prepared extracellular vesicles exhibit classical features of EXOs, such as cup-like shape, around 100 nm diameter, positive protein markers (CD81, TSG101, and Flotillin 1), and ability of internalization. In primary chondrocytes, the treatment of hBMSC-EXOs markedly increases cell viability and proliferation in a dose-dependent manner. Moreover, wound healing assay showed that hBMSC-EXOs accelerate cell migration in primary chondrocytes. JC-1 staining revealed that the mitochondrial membrane potential was enhanced by hBMSC-EXOs, indicating cell apoptosis was decreased in the presence of hBMSC-EXOs. In rabbits with articular cartilage defects, local administration with hBMSC-EXOs facilitates cartilage regeneration as evidenced by gross view and hematoxylin-eosin (H&E) and Saf-O/Fast Green staining. In addition, the International Cartilage Repair Society (ICRS) score was increased by the application of hBMSC-EXOs. Overall, our data indicate that the treatment with hBMSC-EXOs is a suitable cell-free therapy for treating cartilage defects, and these benefits are likely due to improved cell proliferation and migration in chondrocytes.

Citing Articles

Mesenchymal stromal cells-derived extracellular vesicles in cartilage regeneration: potential and limitations.

Pineiro-Ramil M, Gomez-Seoane I, Rodriguez-Cendal A, Fuentes-Boquete I, Diaz-Prado S Stem Cell Res Ther. 2025; 16(1):11.

PMID: 39849578 PMC: 11755911. DOI: 10.1186/s13287-025-04135-6.

Mesenchymal stem cells and their exosomes mitigate osteoarthritis by restoring the balance between proinflammatory Teffs and Tregs.

Liu T, Ran C, Zhao D, Yang F, Guo Q, Yang J Front Aging. 2024; 5:1509014.

PMID: 39629263 PMC: 11611854. DOI: 10.3389/fragi.2024.1509014.

From Bench to Bedside: The Role of Extracellular Vesicles in Cartilage Injury Treatment.

Jin P, Liu H, Chen X, Liu W, Jiang T Biomater Res. 2024; 28:0110.

PMID: 39583872 PMC: 11582190. DOI: 10.34133/bmr.0110.

The Use of Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles in the Treatment of Osteoarthritis: Insights from Preclinical Studies.

Jones M, Jones E, Kouroupis D Bioengineering (Basel). 2024; 11(10).

PMID: 39451337 PMC: 11504680. DOI: 10.3390/bioengineering11100961.

Evaluation of the effect of co-transplantation of collagen-hydroxyapatite bio-scaffold containing nanolycopene and human endometrial mesenchymal stem cell derived exosomes to regenerate bone in rat critical size calvarial defect.

Einabadi M, Izadyari Aghmiuni A, Foroutani L, Ai A, Namini M, Farzin A Regen Ther. 2024; 26:387-400.

PMID: 39045576 PMC: 11263782. DOI: 10.1016/j.reth.2024.02.006.

References

Liu X, Wang L, Ma C, Wang G, Zhang Y, Sun S . Exosomes derived from platelet-rich plasma present a novel potential in alleviating knee osteoarthritis by promoting proliferation and inhibiting apoptosis of chondrocyte via Wnt/β-catenin signaling pathway. J Orthop Surg Res. 2020; 14(1):470. PMC: 6936129. DOI: 10.1186/s13018-019-1529-7. View

Toh W, Lai R, Hui J, Lim S . MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment. Semin Cell Dev Biol. 2016; 67:56-64. DOI: 10.1016/j.semcdb.2016.11.008. View

Makris E, Gomoll A, Malizos K, Hu J, Athanasiou K . Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol. 2014; 11(1):21-34. PMC: 4629810. DOI: 10.1038/nrrheum.2014.157. View

Mustonen A, Nieminen P . Extracellular Vesicles and Their Potential Significance in the Pathogenesis and Treatment of Osteoarthritis. Pharmaceuticals (Basel). 2021; 14(4). PMC: 8065796. DOI: 10.3390/ph14040315. View

Zhang S, Wong K, Ren X, Teo K, Afizah H, Choo A . Mesenchymal Stem Cell Exosomes Promote Functional Osteochondral Repair in a Clinically Relevant Porcine Model. Am J Sports Med. 2022; 50(3):788-800. DOI: 10.1177/03635465211068129. View

van den Borne M, Raijmakers N, Vanlauwe J, Victor J, de Jong S, Bellemans J . International Cartilage Repair Society (ICRS) and Oswestry macroscopic cartilage evaluation scores validated for use in Autologous Chondrocyte Implantation (ACI) and microfracture. Osteoarthritis Cartilage. 2007; 15(12):1397-402. DOI: 10.1016/j.joca.2007.05.005. View

Tang S, Tang T, Gao G, Wei Q, Sun K, Huang W . Bone marrow mesenchymal stem cell-derived exosomes inhibit chondrocyte apoptosis and the expression of MMPs by regulating Drp1-mediated mitophagy. Acta Histochem. 2021; 123(8):151796. DOI: 10.1016/j.acthis.2021.151796. View

Campos Y, Almirall A, Fuentes G, Bloem H, Kaijzel E, Cruz L . Tissue Engineering: An Alternative to Repair Cartilage. Tissue Eng Part B Rev. 2019; 25(4):357-373. DOI: 10.1089/ten.TEB.2018.0330. View

Kalluri R, LeBleu V . The biology function and biomedical applications of exosomes. Science. 2020; 367(6478). PMC: 7717626. DOI: 10.1126/science.aau6977. View

10.

Vonk L, van Dooremalen S, Liv N, Klumperman J, Coffer P, Saris D . Mesenchymal Stromal/stem Cell-derived Extracellular Vesicles Promote Human Cartilage Regeneration . Theranostics. 2018; 8(4):906-920. PMC: 5817101. DOI: 10.7150/thno.20746. View

11.

Cong M, Shen M, Wu X, Li Y, Wang L, He Q . Improvement of sensory neuron growth and survival via negatively regulating PTEN by miR-21-5p-contained small extracellular vesicles from skin precursor-derived Schwann cells. Stem Cell Res Ther. 2021; 12(1):80. PMC: 7831194. DOI: 10.1186/s13287-020-02125-4. View

12.

Gomez-Leduc T, Hervieu M, Legendre F, Bouyoucef M, Gruchy N, Poulain L . Chondrogenic commitment of human umbilical cord blood-derived mesenchymal stem cells in collagen matrices for cartilage engineering. Sci Rep. 2016; 6:32786. PMC: 5015060. DOI: 10.1038/srep32786. View

13.

Wen C, Lin L, Zou R, Lin F, Liu Y . Mesenchymal stem cell-derived exosome mediated long non-coding RNA KLF3-AS1 represses autophagy and apoptosis of chondrocytes in osteoarthritis. Cell Cycle. 2021; 21(3):289-303. PMC: 8855872. DOI: 10.1080/15384101.2021.2019411. View

14.

Barry F . MSC Therapy for Osteoarthritis: An Unfinished Story. J Orthop Res. 2019; 37(6):1229-1235. DOI: 10.1002/jor.24343. View

15.

Zhang S, Chuah S, Lai R, Hui J, Lim S, Toh W . MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity. Biomaterials. 2017; 156:16-27. DOI: 10.1016/j.biomaterials.2017.11.028. View

16.

Mao G, Zhang Z, Hu S, Zhang Z, Chang Z, Huang Z . Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A. Stem Cell Res Ther. 2018; 9(1):247. PMC: 6158854. DOI: 10.1186/s13287-018-1004-0. View

17.

Boyman L, Karbowski M, Lederer W . Regulation of Mitochondrial ATP Production: Ca Signaling and Quality Control. Trends Mol Med. 2019; 26(1):21-39. PMC: 7921598. DOI: 10.1016/j.molmed.2019.10.007. View

18.

Qi H, Liu D, Xiao D, Tian D, Su Y, Jin S . Exosomes derived from mesenchymal stem cells inhibit mitochondrial dysfunction-induced apoptosis of chondrocytes via p38, ERK, and Akt pathways. In Vitro Cell Dev Biol Anim. 2019; 55(3):203-210. DOI: 10.1007/s11626-019-00330-x. View

19.

Harrell C, Markovic B, Fellabaum C, Arsenijevic A, Volarevic V . Mesenchymal stem cell-based therapy of osteoarthritis: Current knowledge and future perspectives. Biomed Pharmacother. 2018; 109:2318-2326. DOI: 10.1016/j.biopha.2018.11.099. View

20.

Wu J, Kuang L, Chen C, Yang J, Zeng W, Li T . miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis. Biomaterials. 2019; 206:87-100. DOI: 10.1016/j.biomaterials.2019.03.022. View