The tissue origin effect of extracellular vesicles on cartilage and bone regeneration
Source abstract
Abstract
Direct implantation of mesenchymal stem cells (MSCs) for cartilage and bone tissue engineering faces challenges, such as immune rejection and loss of cellular viability or functionality. As nanoscale natural particles, exosomes or small extracellular vesicles (EVs) of MSCs have potential to circumvent these problems. It is significant to investigate the impact of the tissue origin of MSCs on the therapeutic bioactivity of their corresponding EVs for cartilage and bone regeneration. Here, rat MSCs isolated from the adipose, bone marrow, and synovium are cultured to obtain their corresponding EVs (ADSC-EVs, BMSC-EVs, and SMSC-EVs, respectively). The ADSC-EVs stimulate the migration, proliferation, and chondrogenic and osteogenic differentiation of BMSCs in vitro as well as cartilage and bone regeneration in a mouse model more than the BMSC-EVs or SMSC-EVs. Proteomics analysis reveals that the tissue origin contributes to the distinct protein profiles among the three types of EVs, which induced cartilage and bone regenerative capacities by potential mechanisms of regulating signaling pathways including focal adhesion, ECM-receptor interaction, actin cytoskeleton, cAMP, and PI3K-Akt signaling pathways. Consequently, these findings provide insight that the adipose may be a superior candidate in EV-based nanomedicine for cartilage and bone regeneration. STATEMENT OF SIGNIFICANCE: Extracelluar vesicles (EVs) of mesenchymal stem cells (MSCs) have been considered as a promising approach in cartilage and bone tissue engineering. In this study, for the first time, we investigated the tissue origin effect of EVs on chondrogenesis and osteogenesis of MSCs in vitro and in vivo. The results demonstrated that EVs of adipose-derived MSCs showed the most efficiency. Meanwhile, protein proteomics revealed the potential mechanisms. We provide a novel evidence that the adipose is a superior reservoir in EV-based nanotechnologies and biomaterials for cartilage and bone regeneration.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Extracellular vesicles in disease · MicroRNA in disease regulation · Osteoarthritis Treatment and Mechanisms
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (67)
Show source-provided references
1. Repair and tissue engineering techniques for articular cartilage10.1038/nrrheum.2014.157 ↗
2. Surgical and tissue engineering strategies for articular cartilage and meniscus repair10.1038/s41584-019-0255-1 ↗
3. Silk as a potential candidate for bone tissue engineering10.1016/j.jconrel.2015.07.031 ↗
4. Extracellular vesicles: potential roles in regenerative medicine10.3389/fimmu.2014.00608 ↗
5. An Analysis of Mesenchymal Stem Cell-Derived Extracellular Vesicles for Preclinical Use10.1021/acsnano.0c01363 ↗
6. A Difunctional Regeneration Scaffold for Knee Repair based on Aptamer-Directed Cell Recruitment10.1002/adma.201605235 ↗
7. A functional biphasic biomaterial homing mesenchymal stem cells for in vivo cartilage regeneration10.1016/j.biomaterials.2014.08.020 ↗
8. Structurally and Functionally Optimized Silk-Fibroin–Gelatin Scaffold Using 3D Printing to Repair Cartilage Injury In Vitro and In Vivo10.1002/adma.201701089 ↗
9. Bioactive Pore-Forming Bone Adhesives Facilitating Cell Ingrowth for Fracture Healing
10. Functionalization of Silk Fibroin Electrospun Scaffolds via BMSC Affinity Peptide Grafting through Oxidative Self-Polymerization of Dopamine for Bone Regeneration10.1021/acsami.8b22123 ↗
11. Extracellular vesicles mediate improved functional outcomes in engineered cartilage produced from MSC/chondrocyte cocultures10.1073/pnas.1815447116 ↗
12. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells10.1038/nm0405-367 ↗
13. Mesenchymal stromal cell-derived extracellular vesicles for regenerative therapy and immune modulation: progress and challenges toward clinical application10.1002/sctm.19-0114 ↗
14. Extracellular vesicles — New tool for joint repair and regeneration10.1038/nrrheum.2015.170 ↗
15. The biology, function, and biomedical applications of exosomes10.1126/science.aau6977 ↗
16. Extracellular Vesicles: unique Intercellular Delivery Vehicles10.1016/j.tcb.2016.11.003 ↗
17. Emerging roles for extracellular vesicles in tissue engineering and regenerative medicine10.1089/ten.teb.2014.0300 ↗
18. Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration10.1016/j.joca.2016.06.022 ↗
19. Exosomes produced from 3D cultures of umbilical cord mesenchymal stem cells in a hollow-fiber bioreactor show improved osteochondral regeneration activity10.1007/s10565-019-09504-5 ↗
20. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity10.1016/j.biomaterials.2017.11.028 ↗
21. Exosomes influence the behavior of human mesenchymal stem cells on titanium surfaces10.1016/j.biomaterials.2019.119571 ↗
22. Tissue-Engineered Bone Immobilized with Human Adipose Stem Cells-Derived Exosomes Promotes Bone Regeneration10.1021/acsami.7b17620 ↗
23. Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration10.7150/thno.31017 ↗
24. miR-23a-3p-abundant small extracellular vesicles released from Gelma/nanoclay hydrogel for cartilage regeneration10.1080/20013078.2020.1778883 ↗
25. Different isolation approaches lead to diverse glycosylated extracellular vesicle populations10.1080/20013078.2019.1621131 ↗
26. Exosomes Produced from 3D Cultures of MSCs by Tangential Flow Filtration Show Higher Yield and Improved Activity10.1016/j.ymthe.2018.09.015 ↗
27. Metabolic signature of extracellular vesicles depends on the cell culture conditions10.1080/20013078.2019.1596669 ↗
28. The Regulatory Functionality of Exosomes Derived from hUMSCs in 3D Culture for Alzheimer's Disease Therapy10.1002/smll.201906273 ↗
29. Bioglass enhances the production of exosomes and improves their capability of promoting vascularization
30. KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a10.1038/s41467-019-09720-x ↗
31. Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species10.1186/s13287-015-0116-z ↗
32. Lineage-specific exosomes could override extracellular matrix mediated human mesenchymal stem cell differentiation10.1016/j.biomaterials.2018.08.027 ↗
33. Different tenogenic differentiation capacities of different mesenchymal stem cells in the presence of BMP-1210.1186/s12967-015-0560-7 ↗
34. Endosomal signalling via exosome surface TGFβ-110.1080/20013078.2019.1650458 ↗
35. Molecular Profiling and Functional Analysis of Macrophage-Derived Tumor Extracellular Vesicles10.1016/j.celrep.2019.05.008 ↗
36. Mitochondrial Dysfunction and Morphological Abnormality in Keloid Fibroblasts10.1089/wound.2019.0988 ↗
37. Metabolic reprogramming in keloid fibroblasts: aerobic glycolysis and a novel therapeutic strategy10.1016/j.bbrc.2018.01.068 ↗
38. Universal sample preparation method for proteome analysis10.1038/nmeth.1322 ↗
39. UniProt: the universal protein knowledgebase10.1093/nar/gky092 ↗
40. The extracellular matrix: tools and insights for the "omics" era10.1016/j.matbio.2015.06.003 ↗
41. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement10.1080/14653240600855905 ↗
42. Polycaprolactone electrospun mesh conjugated with an MSC affinity peptide for MSC homing in vivo10.1016/j.biomaterials.2012.01.033 ↗
43. Active Wnt proteins are secreted on exosomes10.1038/ncb2574 ↗
44. Reassessment of Exosome Composition10.1016/j.cell.2019.02.029 ↗
45. Exosomes10.1146/annurev-biochem-013118-111902 ↗
46. Anchor peptide captures, targets, and loads exosomes of diverse origins for diagnostics and therapy10.1126/scitranslmed.aat0195 ↗
47. Lymphocyte-Derived Exosomal MicroRNAs Promote Pancreatic β Cell Death and May Contribute to Type 1 Diabetes Development10.1016/j.cmet.2018.09.011 ↗
48. miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis10.1016/j.biomaterials.2019.03.022 ↗
49. Multilineage potential of adult human mesenchymal stem cells10.1126/science.284.5411.143 ↗
50. Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model10.7150/thno.17133 ↗
51. Human Adipose-Derived Stem Cell Conditioned Media and Exosomes Containing MALAT1 Promote Human Dermal Fibroblast Migration and Ischemic Wound Healing10.1089/wound.2017.0775 ↗
52. Bone marrow mesenchymal stem cell-derived exosomes promote tendon regeneration by facilitating the proliferation and migration of endogenous tendon stem/progenitor cells10.1016/j.actbio.2020.01.051 ↗
53. Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis10.1186/s13287-017-0510-9 ↗
54. Differential Wound Healing Capacity of Mesenchymal Stem Cell-Derived Exosomes Originated From Bone Marrow, Adipose Tissue and Umbilical Cord Under Serum- and Xeno-Free Condition10.3389/fmolb.2020.00119 ↗
55. Autologous Fractionated Adipose Tissue as a Natural Biomaterial and Novel One-Step Stem Cell Therapy for Repairing Articular Cartilage Defects10.3389/fcell.2020.00694 ↗
56. Enhanced MSC chondrogenesis following delivery of TGF-β3 from alginate microspheres within hyaluronic acid hydrogels in vitro and in vivo10.1016/j.biomaterials.2011.05.033 ↗
57. Hijacking the Cellular Mail: exosome Mediated Differentiation of Mesenchymal Stem Cells10.1155/2016/3808674 ↗
58. Identification of the Human Skeletal Stem Cell10.1016/j.cell.2018.07.029 ↗
59. Direct 3D Printing of High Strength Biohybrid Gradient Hydrogel Scaffolds for Efficient Repair of Osteochondral Defect10.1002/adfm.201706644 ↗
60. Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model10.5966/sctm.2015-0285 ↗
61. Fibronectin Enhances Cartilage Repair by Activating Progenitor Cells Through Integrin α5β1 Receptor10.1089/ten.tea.2017.0322 ↗
62. Signaling of extracellular matrices for tissue regeneration and therapeutics10.1007/s13770-016-9075-0 ↗
63. Regulation of chondrocyte differentiation by the actin cytoskeleton and adhesive interactions10.1002/jcp.21110 ↗
64. TGFβ1-Induced Differentiation of Human Bone Marrow-Derived MSCs Is Mediated by Changes to the Actin Cytoskeleton10.1155/2018/6913594 ↗
65. Inhibiting actin depolymerization enhances osteoblast differentiation and bone formation in human stromal stem cells10.1016/j.scr.2015.06.009 ↗
66. cAMP/PKA pathway activation in human mesenchymal stem cells in vitro results in robust bone formation in vivo10.1073/pnas.0711190105 ↗
67. An activator of the cAMP/PKA/CREB pathway promotes osteogenesis from human mesenchymal stem cells10.1002/jcp.24171 ↗