Corneal Regeneration Using Adipose-Derived Mesenchymal Stem Cells
Abstract
:1. Introduction: Adipose-Derived Mesenchymal Stem Cells (ADSC)
2. Corneal Epithelium ADSC Regeneration: Preclinical & Clinical Evidence
2.1. Preclinical Evidence
2.1.1. ADSC for the Treatment of DED
2.1.2. ADASC for the Treatment of Limbal Stem Cell Deficiency and Corneal Epithelial Damage
2.1.3. Cell-Free Therapy with ADSC-Derived Extracellular Vesicles
2.2. Clinical Evidence
ADASC for Corneal Epithelium Regeneration
3. Corneal Stroma ADSC Regeneration: Preclinical & Clinical Evidence
3.1. Preclinical Evidence
3.1.1. Available Stem Cells for Corneal Stroma Cellular Therapy
3.1.2. Corneal Stroma Regeneration by MSC Therapy Strategies without Scaffold
- (A)
- Ocular Surface Implantation of Stem Cells
- (B)
- Intrastromal Implantation of Stem Cells
- (C)
- Anterior Chamber Injection of Stem Cells
- (D)
- Intravenous Injection of Stem Cells
3.1.3. Cell-Free Therapy with MSC-Derived Extracellular Vesicles
3.2. Clinical Evidence
4. Corneal Endothelium ADSC Regeneration: Preclinical Evidence
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Growth Factors to Induce Differentiation | Markers Used to Confirm Differentiation | |
---|---|---|
Corneal Epithelium | EGF, FGF2, KGF | For epithelium: CK3, CK18, E-cadherin For limbus: ABCG2, p63, CK15 |
Corneal Stroma Keratocytes | FGF2 in keratocyte coculture | Collagens type I, type VI and keratocan |
Corneal Endothelium | FGF2, Noggin, Heregulin β1, IGF1, PDGFBB, DKK-2 | S100, Na+/K+ ATPase, Cadherin and ZO1 |
ClinicalTrials.gov Number/Reference | Target Disease | Type of MSC/Route of Administration | Number of Patients | Maximum Follow-Up (Months) | Outcomes after Cell-Based Therapy |
---|---|---|---|---|---|
Weng et al., 2012 [84] | GVHD-DED | Allogeneic BM-MSC/intravenous injection | 22 | 33 | No adverse events Symptoms (OSDI) and signs (NIH consensus criteria, Schirmer’s test) improved in 55% of cases. |
NCT01562002 Calonge et al., 2019 [52] | LSCD | Allogeneic BM-MSC/cells cultivated on an amniotic membrane and transplanted onto the ocular surface | 27 | 12 | No adverse events The corneal epithelial phenotype improved in patients treated with MSCT (71.4%). Global success was 76.5–85.7% for MSCT at 6–12 months without significant differences with CLET. |
NCT03878628 Møller-Hansen et al., 2021 [83] | Aqueous deficient DED | Allogeneic ADSC Transconjunctival injection | 7 | 4 | No adverse events Symptoms (OSDI) and signs (osmolarity, TBUT, Schirmer’s test, tendency in corneal staining) improved. |
NTC04213248 Zhou et al., 2022 [77] | GVHD- DED | Exosomes isolated from allogeneic UC-MSC/administered as eye drops | 14 | 0.5 | No adverse events Symptoms (OSDI) and signs (TBUT, Schirmer’s test, corneal staining) improved. |
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Alió del Barrio, J.L.; De la Mata, A.; De Miguel, M.P.; Arnalich-Montiel, F.; Nieto-Miguel, T.; El Zarif, M.; Cadenas-Martín, M.; López-Paniagua, M.; Galindo, S.; Calonge, M.; et al. Corneal Regeneration Using Adipose-Derived Mesenchymal Stem Cells. Cells 2022, 11, 2549. https://doi.org/10.3390/cells11162549
Alió del Barrio JL, De la Mata A, De Miguel MP, Arnalich-Montiel F, Nieto-Miguel T, El Zarif M, Cadenas-Martín M, López-Paniagua M, Galindo S, Calonge M, et al. Corneal Regeneration Using Adipose-Derived Mesenchymal Stem Cells. Cells. 2022; 11(16):2549. https://doi.org/10.3390/cells11162549
Chicago/Turabian StyleAlió del Barrio, Jorge L., Ana De la Mata, María P. De Miguel, Francisco Arnalich-Montiel, Teresa Nieto-Miguel, Mona El Zarif, Marta Cadenas-Martín, Marina López-Paniagua, Sara Galindo, Margarita Calonge, and et al. 2022. "Corneal Regeneration Using Adipose-Derived Mesenchymal Stem Cells" Cells 11, no. 16: 2549. https://doi.org/10.3390/cells11162549