Melatonin Treatment Improves Mesenchymal Stem Cells Therapy by Preserving Stemness during Long-term In Vitro Expansion
Open accessAbstract
Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of MSCs, resulting in failure of MSCs therapy. Here, we report a melatonin-based strategy to improve cell therapy of in vitro cultured MSCs. Among four small molecules with anti-aging and stem cell-protection properties (rapamycin, resveratrol, quercetin and melatonin), colony forming, proliferation, and osteogenic differentiation assay showed that melatonin was the most efficient to preserve self-renewal and differentiation properties of rat bone marrow MSCs (BMMSCs) after long-term passaging. Functional assays confirmed melatonin treatment did not affect the colony forming, proliferation and osteogenic differentiation of BMMSCs cultured for 1 or 4 passages, but largely prevented the decline of self-renew and differentiation capacity of BMMSCs cultured for 15 passages in vitro. Furthermore, heterotopic osteogenesis assay, critical size calvarial defects repair assay, osteoporosis treatment and experimental colitis therapy assay strongly certified that melatonin preserved the therapeutic effect of long-term passaged BMMSCs on bone regeneration and immunotherapy in vivo. Mechanistically, melatonin functioned by activating antioxidant defense system, inhibiting the pathway of cell senescence, and preserving the expression of gene governing the stemness. Taken together, our findings showed that melatonin treatment efficiently prevented the dysfunction and therapeutic failure of BMMSCs after long-term passaging, providing a practical strategy to improve the application of BMMSCs in tissue engineering and cytotherapy.
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Melatonin supplementation decreases cellular senescence, preserves self-renewal, and activates antioxidant defence pathways in MSCs.
“In this context, decreased cellular senescence, preserved self-renewal and activation of antioxidant defence pathways have all been observed after melatonin supplementation [460,461].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [461]
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- Authors
- Shuai, Y., Liao, L., Su, X., Yu, Y., Shao, B., Jing, H., Zhang, X., Deng, Z., & Jin, Y.
- Affiliations
- Air Force Medical University (CN)
- Stomatology Hospital (CN)
- Chongqing Medical University (CN)
- Xijing Hospital (CN)
- Corresponding author
- Shuai, Yi
- Liao, Li
- Venue
- Theranostics
- Publisher
- Ivyspring International Publisher
- Published
- 2016
- Volume
- 6
- Issue
- 11
- Pages
- 1899-1917
- ISSN
- 1838-7640 (ISSN-L)
- PMC
- PMC4997245
- OpenAlex
- W2513023815
- Cited by
- 137
- References
- 74
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 16 · 2023: 12 · 2022: 11 · 2021: 23 · 2020: 15 · 2019: 17 · 2018: 15 · 2017: 12 · 2016: 2
- FWCI
- 11.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Theranostics (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- melatonin, mesenchymal stem cells, bone marrow mesenchymal stem cells, osteogenic differentiation, self-renewal, cellular senescence, antioxidant defense, bone regeneration, osteoporosis, experimental colitis, rapamycin, resveratrol, quercetin, cytotherapy
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Colitis, Disease Models, Animal, Humans, Melatonin, Osteoporosis, Serial Passage, Rats, Sprague-Dawley, Cell Transplantation, Cell Culture Techniques, Tissue Engineering, Cell Proliferation, Fractures, Bone, Mesenchymal Stem Cells
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