Bone marrow derived-mesenchymal stem cell improves diabetes-associated fatty liver via mitochondria transformation in mice
Open accessAbstract
Background: Non-alcoholic fatty liver disease (NAFLD) has become a global epidemic disease. Its incidence is associated with type 2 diabetes mellitus (T2DM). Presently, there is no approved pharmacological agents specially developed for NAFLD. One promising disease-modifying strategy is the transplantation of stem cells to promote metabolic regulation and repair of injury. Method: In this study, a T2DM model was established through 28-week high-fat diet (HFD) feeding resulting in T2DM-associated NAFLD, followed by the injection of bone marrow mesenchymal stem cells (BMSCs). The morphology, function, and transfer of hepatocyte mitochondria were evaluated in both vivo and in vitro. Results: BMSC implantation resulted in the considerable recovery of increasing weight, HFD-induced steatosis, liver function, and disordered glucose and lipid metabolism. The treatment with BMSC transplantation was accompanied by reduced fat accumulation. Moreover, mitochondrial transfer was observed in both vivo and vitro studies. And the mitochondria-recipient steatotic cells exhibited significantly enhanced OXPHOS activity, ATP production, and mitochondrial membrane potential, and reduced reactive oxygen species levels, which were not achieved by the blocking of mitochondrial transfer. Conclusion: Mitochondrial transfer from BMSCs is a feasible process to combat NAFLD via rescuing dysfunction mitochondria, and has a promising therapeutic effect on metabolism-related diseases.
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An increasing number of studies support the use of MSCs to treat liver fibrosis by transferring mitochondria.
“An increasing number of studies nowadays support the use of MSCs to treat liver fibrosis by transferring Mt [117, 120, 121].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [121]
The Results section on mitochondrial transfer reports that BMSCs transferred mitochondria to hepatocytes and suppressed steatosis. The Discussion also mentions a prior study of BMSCs in liver fibrosis, but does not say mitochondrial transfer treated fibrosis. This paper’s own findings concern diabetes-associated fatty liver in mice, not treatment of liver fibrosis. (LLM, conf=0.87)
Experimental — accuracy not yet measuredMSCs improved liver steatosis and glucose and lipid metabolism disorder by transferring mitochondria to steatotic cells.
“Similarly, MSCs improved liver steatosis and glucose and lipid metabolism disorder by transferring Mt to steatotic cells [121].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [121]
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- Authors
- Bi, Y., Guo, X., Zhang, M., Zhu, K., Shi, C., Fan, B., Wu, Y., Yang, Z., & Ji, G.
- Affiliations
- Chinese Academy of Sciences (CN)
- Henan Medical University (CN)
- Corresponding author
- Guo, Xuejun
- Ji, Guangju
- Venue
- Stem Cell Research & Therapy
- Published
- 2021-12
- Volume
- 12
- Issue
- 1
- Pages
- 602-602
- ISSN
- 1757-6512 (ISSN-L)
- PMC
- PMC8665517
- OpenAlex
- W4200456992
- Cited by
- 82
- References
- 60
- Citations by year
- 2026: 8 · 2025: 22 · 2024: 25 · 2023: 18 · 2022: 9
- FWCI
- 7.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Key Research and Development Project (2019YFA0100400)
- National Foundation of Sciences and Technology (31971051, 31771562)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- bone marrow mesenchymal stem cells, non-alcoholic fatty liver disease, type 2 diabetes, mitochondrial transfer, hepatocyte mitochondria, steatosis, high-fat diet, stem cell transplantation, oxidative phosphorylation, reactive oxygen species, mitochondrial membrane potential, ATP production, glycolipid metabolism
- MeSH terms
- Animals, Bone Marrow, Diabetes Mellitus, Type 2, Liver, Mitochondria, Mice, Diet, High-Fat, Mesenchymal Stem Cells, Non-alcoholic Fatty Liver Disease
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