Extracellular Vesicles from Mesenchymal Stem Cells as Potential Treatments for Osteoarthritis
Abstract
:1. Introduction
2. Pathophysiology of OA
3. Treatment of OA
3.1. Osteoarthritis Management and Current Therapy
3.2. Pharmacological and Non-Pharmacological Therapy
4. Mesenchymal Stem Cells
4.1. The Source of Mesenchymal Stem Cells, Isolation and Characterization
4.2. Mesenchymal Stem Cell-Based Therapy
4.3. Mesenchymal Stem Cell-Based Therapy in Osteoarthritis Treatment
5. Extracellular Vesicles
5.1. Extracellular Vesicles Biogenesis
5.2. Isolation and Characterization of Extracellular Vesicles
5.3. Extracellular Vesicles in Osteoarthritis
5.4. Therapeutic Potential of MSC-Drived EV in Osteoarthritis
5.5. The Promise and Challenges of EV as a Therapeutic Delivery System
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Isolation Method | Advantages | Disadvantages | Yield |
---|---|---|---|
Differential centrifugation/ultracentrifugation | EV subtypes isolation [94], cost effective | Time consuming, less effective for body fluid with high viscosity, low purity | Intermediate |
Precipitation | High EV recovery | Low specificity, less accurate in terms of size distribution, and low purity | High |
Size exclusion chromatography | Precise, structurally unaffected of EV | Quantitatively inefficient, and time consuming | Intermediate |
Ultrafiltration | EV subtypes isolation based on size [93], and cost effective | Low specificity, and time consuming | Low [95] |
Field-flow fractionation (FFF) | High specificity [96], accurate EV size distribution and High EV integrity | Small volume of sample | Intermediate |
Commercial kits (eg: ExoQuick, ExoMir kit) | High EV integrity, convenient procedure [97] | Costly, low purity and low reproducibility | Intermediate |
Immunoprecipitation | High purity [98], EV subtypes isolation based on protein marker [99] | Costly and time consuming [100] | Intermediate |
Immunoaffinity columns | Fast and high reproducibility | Low specificity [101] | Intermediate |
Techniques | Advantages | Disadvantages | |
---|---|---|---|
Physical | Electron microscopy (SEM and TEM) | Allow assessment of EV morphology | Time consuming, single parametric phenotypic EV characterization |
Nanoparticle tracking (NTA) | Allows assessment of individual EV in terms of size and concentration of EV | Starting amount of EV and contaminants may affect the accuracy of results | |
Dynamic light scattering (DLS) | Fast, small starting amount of EV, provides size range of EV | Limits the analysis of individual EV | |
Chemical, biological and compositional analysis | Flow cytometry (FCM) | Quantitative and qualitative analysis, EV-subtypes analysis, permits analysis of large numbers of samples at a time | Occurrence of swarm detection, overlapping background noise and minimal detection limits |
Western blotting | Assess markers of EV as well as internal proteins of EV | Limited in translational studies, the quality of antibodies used may compromise the specificity of the analysis |
Type of EV | Model | Marker | Time Point of Assay | Specific Characteristic of In Vivo or In Vitro Studies | Findings | References |
---|---|---|---|---|---|---|
Exosome derived from human bone marrow-derived MSCs (MCS-Exos and MSC-miR92a-3p-Exos) |
|
|
|
|
| [135] |
Exosomes and microparticles (MP) derived from murine bone marrow-derived MSCs |
|
|
|
|
| [131] |
Exosomes derived from human embryonic stem cell (HuECS)-derived MSCs | Rat (osteochondral defect) | Exosomes: CD81, TSG101 | Intra-articular injections of exosomes or PBS were weekly administered at the site of osteochondral defect for 12 weeks and harvested at weeks 6 and 12 | 100 μg exosomes was administered |
| [132] |
Exosomes derived from human synovial membrane-derived MSCs (SMMSC-Exos) and induced pluripotent stem cell-derived MSCs (iMSC-Exos) | Mouse (collagenase-induced OA) |
|
|
|
| [133] |
EVs secreted from human bone marrow-derived MSCs (BMMSC-Evs) | Human knee cartilage of OA patient (TNF- α -induced inflammatory) | BMMSC-Evs: CD9 and CD63 |
|
|
| [134] |
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Mohd Noor, N.A.; Abdullah Nurul, A.; Ahmad Mohd Zain, M.R.; Wan Nor Aduni, W.K.; Azlan, M. Extracellular Vesicles from Mesenchymal Stem Cells as Potential Treatments for Osteoarthritis. Cells 2021, 10, 1287. https://doi.org/10.3390/cells10061287
Mohd Noor NA, Abdullah Nurul A, Ahmad Mohd Zain MR, Wan Nor Aduni WK, Azlan M. Extracellular Vesicles from Mesenchymal Stem Cells as Potential Treatments for Osteoarthritis. Cells. 2021; 10(6):1287. https://doi.org/10.3390/cells10061287
Chicago/Turabian StyleMohd Noor, Nur Azira, Asma Abdullah Nurul, Muhammad Rajaei Ahmad Mohd Zain, Wan Khairunnisaa Wan Nor Aduni, and Maryam Azlan. 2021. "Extracellular Vesicles from Mesenchymal Stem Cells as Potential Treatments for Osteoarthritis" Cells 10, no. 6: 1287. https://doi.org/10.3390/cells10061287
APA StyleMohd Noor, N. A., Abdullah Nurul, A., Ahmad Mohd Zain, M. R., Wan Nor Aduni, W. K., & Azlan, M. (2021). Extracellular Vesicles from Mesenchymal Stem Cells as Potential Treatments for Osteoarthritis. Cells, 10(6), 1287. https://doi.org/10.3390/cells10061287