The Therapeutic Potential of Exosomes from Mesenchymal Stem Cells in Multiple Sclerosis
Abstract
:1. Multiple Sclerosis
2. Mesenchymal Stem Cells and Their Secretome
3. Exosomes
3.1. Exosome Biosynthesis
3.1.1. MVB Formation
3.1.2. Cargo Sorting
3.1.3. MVB Transport, Fusion with the Plasma Membrane and Exocytosis
3.2. Interaction with Recipient Cell
3.3. Effects of MSC Exosomes in the CNS
4. Pre-Clinical Data of Exosomes from MSCs in MS Models
Author, Country, Year | Species | MS Model | Stem Cell Type | Stem Cell Source | EV/Exosome Dose | Exosome Numbers | Administration Mode | Time of Delivery after Disease Induction | Follow-Up | Effect |
---|---|---|---|---|---|---|---|---|---|---|
Li et al., China, 2019 [64] | Rats | EAE | BM-MSCs | Rats | 100 μg, 400 μg | NS | IV | 24 h | 14 d | Modulation microglia M1–M2, Reduced demyelination, Improved outcomes |
Laso-Garcia, Spain, 2018 [65] | Mice | TMEV | Adipose-derived MSCs | Human | 25 μg | NS | IV | 60 d | 75 d | Reduced neuroinflammation, Reduced demyelination, Improved motoric function |
Fathollahi, Iran, 2021 [66] | Mice | EAE | Adipose-derived MSCs | Mice | 10 g | NS | Intranasal | 15–25 d | 27 d | Reduced demyelination, Amelioration of clinical symptoms, Modulation of regulatory T-cells |
Zhang, USA, 2022 [60] | Mice | Cuprizone and EAE | BM-MSCs | Rhesus monkey | IV | EAE: 10 d, Cuprizone: 5 weeks | EAE: 35 d, Cuprizone: 2 weeks | Exosomes within CNS after 4 h, Modulation microglia M1–M2, Increase OPC differentiation and myelination, Improved outcomes | ||
Farinazzo, Italy, 2018 [69] | Mice | EAE | Adipose-derived MSCs | Mice | 5 g | NS | IV | Preventive: 3, 8 and 13 d, Therapeutic: 12, 16 and 20 d | 36 d | In preventive protocol: Inhibition of microglial activation, Decreased T-cell activation, Decreased demyelination, No effect in therapeutic protocol |
Rajan, Italy, 2017 [70] | Mice | EAE | Dental tissue | Human | 24 g | NS | IV | 14 d | 28 d | Reduced neuroinflammation, Inhibition TLR4 pathway, Improved outcomes |
Jafarinia, Iran, 2020 [71] | Mice | EAE | Adipose-derived MSCs | Human | 60 μg | NS | IV | 10 d | 30 d | Reduced neuroinflammation, Reduced demyelination, Improved outcomes |
Koohsari, Iran, 2021 [72] | Mice | EAE | Umbilical cord | Human | 50 μg | NS | IV | 9 d | 30 d | Reduced CNS leukocyte infiltration, Reduced inflammatory cytokines, Improved outcomes |
Riazifar, USA, 2019 [73] | Mice | EAE | BM-MSCs | Human | 150 μg | NS | IV | 18 d | 40 d | Decreased microglia infiltration, Less demyelination |
5. Exosomes from MSCs in MS—A Clinical Perspective
5.1. Data on Safety
5.2. Mode of Administration
5.3. Practical Issues of Exosomes as a Therapeutic Product
5.3.1. Foreign Exosomes from Ex Vivo Expansion
5.3.2. Large Scale Production
5.3.3. Modification of MSCs
5.3.4. Translation from Pre-Clinical Models
6. Conclusive Remarks
Funding
Conflicts of Interest
References
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Author, Country, Year | Condition | Administration Mode | N Patients | Study Type | Source Allogeneic MSCs | Dose | N Treatments | Follow-Up | Safety | Efficacy Compared to Control |
---|---|---|---|---|---|---|---|---|---|---|
Nassar, Egypt, 2016 [74] | Chronic kidney disease | IV/Intraarterial | 40 | Randomized, controlled | Umbilical cord | 100 g/kg bodyweight | 2 | 12 months | No significant AEs | Improved GFR, Decreased pro-inflammatory cytokines |
Sengupta, USA, 2020 [75] | COVID-19 and moderate/severe ARDS | IV | 24 | Single group | BM | NS (15 mL) | 1 | 14 days | No AE attributable to IMP | NA (no control group) |
Kordelas, Germany, 2014 [76] | GVHD | IV | 1 | Case report | BM | 0.1–4 units (one unit = 1.3–3.5 × 1010 exosomes) | 7 | 7 weeks | No AE attributable to IMP | NA (no control group) |
Shi, China, 2021 [77] | Healthy volunteers | Inhalation | 24 | Single group | Adipose-derived MSCs | 2 × 108 particles to 16 × 108 particles | 1 | 7 days | Two asymptomatic bradycardia. No SAE | INA (no control group) |
East, USA, 2020 [78] | Osteoarthritis | Injection | 33 | Single group | BM | 60 × 1011 exosomes | 1 | 6 months | No AE attributable to IMP | NA (no control group) |
Cho, South Korea, 2020 [79] | Hyperpigmentation | Ointment | 24 | Randomized, controlled | Adipose-derived MSCs | 2 × 1010 particles/mL | Twice per day for 8 weeks | 8 weeks | No AE attributable to IMP | Reduced amounts of melanin |
Kwon, South Korea, 2020 [80] | Skin scars | Gel | 25 | Single group, split face | Adipose-derived MSCs | 1.6–9.8 × 1010 exosomes/mL | 4 | 6 weeks | No AE attributable to IMP | Milder erythema on the exosome-treated side, Atrophic scar volume was significantly decreased |
Xie, China, 2023 [81] | Alzheimer | Intranasal | 9 | Dose escalation | Adipose-derived MSCs | 2–8 × 108 exosomes | Twice/week for 12 weeks | 48 weeks | No AE attributable to IMP | NA (no control group) |
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Kråkenes, T.; Sandvik, C.E.; Ytterdal, M.; Gavasso, S.; Evjenth, E.C.; Bø, L.; Kvistad, C.E. The Therapeutic Potential of Exosomes from Mesenchymal Stem Cells in Multiple Sclerosis. Int. J. Mol. Sci. 2024, 25, 10292. https://doi.org/10.3390/ijms251910292
Kråkenes T, Sandvik CE, Ytterdal M, Gavasso S, Evjenth EC, Bø L, Kvistad CE. The Therapeutic Potential of Exosomes from Mesenchymal Stem Cells in Multiple Sclerosis. International Journal of Molecular Sciences. 2024; 25(19):10292. https://doi.org/10.3390/ijms251910292
Chicago/Turabian StyleKråkenes, Torbjørn, Casper Eugen Sandvik, Marie Ytterdal, Sonia Gavasso, Elisabeth Claire Evjenth, Lars Bø, and Christopher Elnan Kvistad. 2024. "The Therapeutic Potential of Exosomes from Mesenchymal Stem Cells in Multiple Sclerosis" International Journal of Molecular Sciences 25, no. 19: 10292. https://doi.org/10.3390/ijms251910292
APA StyleKråkenes, T., Sandvik, C. E., Ytterdal, M., Gavasso, S., Evjenth, E. C., Bø, L., & Kvistad, C. E. (2024). The Therapeutic Potential of Exosomes from Mesenchymal Stem Cells in Multiple Sclerosis. International Journal of Molecular Sciences, 25(19), 10292. https://doi.org/10.3390/ijms251910292