Engineering exosomes derived from subcutaneous fat MSCs specially promote cartilage repair as miR-199a-3p delivery vehicles in osteoarthritis
Open accessAbstract
Abstract Osteoarthritis (OA) is a degenerative joint disease involving cartilage. Exosomes derived from Mesenchymal stem cells (MSCs) therapy improves articular cartilage repair, but subcutaneous fat (SC) stromal cells derived exosomes (MSCs SC -Exos), especially engineering MSCs SC -Exos for drug delivery have been rarely reported in OA therapy. This objective of this study was to clarify the underlying mechanism of MSCs SC -Exos on cartilage repair and therapy of engineering MSCs SC -Exos for drug delivery in OA. MSCs SC -Exos could ameliorate the pathological severity degree of cartilage via miR-199a-3p, a novel molecular highly enriched in MSCs SC -Exos, which could mediate the mTOR-autophagy pathway in OA rat model. Intra-articular injection of antagomiR-199a-3p dramatically attenuated the protective effect of MSCs SC -Exos-mediated on articular cartilage in vivo. Furthermore, to achieve the superior therapeutic effects of MSCs SC -Exos on injured cartilage, engineering exosomes derived from MSCs SC as the chondrocyte-targeting miR-199a-3p delivery vehicles were investigated in vitro and in vivo. The chondrocyte-binding peptide (CAP) binding MSCs SC -Exos could particularly deliver miR-199a-3p into the chondrocytes in vitro and into deep articular tissues in vivo, then exert the excellent protective effect on injured cartilage in DMM-induced OA mice. As it is feasible to obtain human subcutaneous fat from healthy donors by liposuction operation in clinic, meanwhile engineering MSCs SC -Exos to realize targeted delivery of miR-199a-3p into chondrocytes exerted excellent therapeutic effects in OA animal model in vivo. Through combining MSCs SC -Exos therapy and miRNA therapy via an engineering approach, we develop an efficient MSCs SC -Exos-based strategy for OA therapy and promote the application of targeted-MSCs SC -Exos for drug delivery in the future. Graphical Abstract
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miRNAs carried by MSC-Exos specifically bind to mRNA in target cells, inhibiting post-transcriptional gene expression and influencing osteoblast proliferation, differentiation, and apoptosis.
“The miRNAs carried by MSC-Exos specifically bind to mRNA in target cells, inhibiting post-transcriptional gene expression and consequently influencing physiological functions, including osteoblast proliferation, differentiation, and apoptosis [[20], [21], [22], [23], [24]].”
From Hydrogel scaffold encapsulating MSC-Exos and ZIF-8 promotes bone regeneration via coordinating osteogenesis and immunomodulation (2025) · cites this paper as [21]
The Discussion (page unavailable) says exosomal miRNAs bind target mRNA and disrupt gene expression. The Results (page unavailable) show exosomal miR-199a-3p suppressing mTOR expression in chondrocytes, not osteoblasts. The paper discusses chondrocyte proliferation and apoptosis but does not establish effects on osteoblast proliferation, differentiation, or apoptosis. (LLM, conf=0.88)
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References 76 · Cited by 109
- Authors
- Zhao, S., Xiu, G., Wang, J., Wen, Y., Lu, J., Wu, B., Wang, G., Yang, D., Ling, B., Du, D., & Xu, J.
- Affiliations
- Tongji University (CN)
- Yunnan University (CN)
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Ling, Bin
- Du, Dajiang
- Xu, Jun
- Venue
- Journal of Nanobiotechnology
- Published
- 2023-09-22
- Volume
- 21
- Issue
- 1
- Pages
- 341-341
- ISSN
- 1477-3155 (ISSN-L)
- PMC
- PMC10515007
- OpenAlex
- W4386944090
- Cited by
- 109
- References
- 76
- Citations by year
- 2026: 35 · 2025: 44 · 2024: 27 · 2023: 3
- FWCI
- 22.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Nanobiotechnology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Science Foundation of Shanghai (21ZR1448000)
- National Natural Science Foundation of China (32170986, 31671055, 81901950)
- Innovation Program of Shanghai Municipal Education Commission (2023ZKZD31)
- the National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2018ZX09201002-005)
- the Xu Jun’s expert work station (202005AF150050)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- osteoarthritis, exosomes, mesenchymal stem cells, miR-199a-3p, cartilage repair, exosome engineering, intra-articular injection, miRNA-based therapy
- MeSH terms
- Animals, Humans, Osteoarthritis, MicroRNAs, Subcutaneous Fat, Mice, Rats, Exosomes, Mesenchymal Stem Cells
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