The DOI matches its Crossref record; 70 of the 71 references it cites were found in a registry or an index.
Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration
Abstract
Transplantation of synovial fluid-derived mesenchymal stem cells (SF-MSCs) is a viable therapy for cartilage degeneration of osteoarthritis (OA). But controlling chondrogenic differentiation of the transplanted SF-MSCs in the joints remains a challenge. Kartogenin (KGN) is a small molecule that has been discovered to induce differentiation of SF-MSCs to chondrocytes both in vitro and in vivo. The clinical application of KGN however is limited by its low water solubility. KGN forms precipitates in the cell, resulting in low effective concentration and thus limiting its chondrogesis-promoting activity. Here we report that targeted delivery of KGN to SF-MSCs by engineered exosomes leads to even dispersion of KGN in the cytosol, increases its effective concentration in the cell, and strongly promotes the chondrogenesis of SF-MSCs in vitro and in vivo. Fusing an MSC-binding peptide E7 with the exosomal membrane protein Lamp 2b yields exosomes with E7 peptide displayed on the surface (E7-Exo) that has SF-MSC targeting capability. KGN delivered by E7-Exo efficiently enters SF-MSCs and induces higher degree of cartilage differentiation than KGN alone or KGN delivered by exosomes without E7. Co-administration of SF-MSCs with E7-Exo/KGN in the knee joints via intra-articular injection also shows more pronounced therapeutic effects in a rat OA model than KGN alone or KGN delivered by exosomes without E7. Altogether, transplantation of SF-MSCs with in situ chondrogenesis enabled by E7-Exo delivered KGN holds promise towards as an advanced stem cell therapy for OA.
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“In addition, exosomes can be genetically engineered, chemically surface modified or enzymatically engineered to introduce peptides and proteins to enhance their targeting ability [42, 83–86].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [86]
In the citing paper
“In a rat model, KGN loaded by engineered exosomes also showed better therapeutic effects than KGN alone [89].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [89]
In the citing paper
“Another study showed that targeting Kartogenin (KGN) to synovial fluid-derived mesenchymal stem cells (SF-MSCs) by engineered exosomes resulted in uniform dispersion of KGN in the cytoplasmic matrix, increased concentration in the target, and significantly promoted chondrogenesis of SF-MSCs.”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [89]
Citations
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Extracellular vesicle therapy for obesity-induced NAFLD: a comprehensive review of current evidence
Zhang, J., Ma, B., Wang, Z., Chen, Y., Li, C., & Dong, Y. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-023-01292-0 · Cited by 17
Metadata
- Authors
- Xu, X., Liang, Y., Li, X., Ouyang, K., Wang, M., Cao, T., Li, W., Liu, J., Xiong, J., Li, B., Xia, J., Wang, D., & Duan, L.
- Affiliations
- Shenzhen University Health Science Center (CN)
- Chinese University of Hong Kong (HK)
- National University of Singapore (SG)
- Southern University of Science and Technology (CN)
- Corresponding author
- Wang, Manyi
- Xia, Jiang
- Wang, Daping
- Duan, Li
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 269
- Pages
- 120539
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W3100184771
- Cited by
- 377
- References
- 71
- Citations by year
- 2026: 39 · 2025: 87 · 2024: 79 · 2023: 79 · 2022: 64 · 2021: 28
- FWCI
- 32.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Keywords
- kartogenin, exosomes, chondrogenesis, cartilage regeneration, osteoarthritis, exosome-mediated drug delivery, E7 peptide, Lamp2b, intra-articular injection, stem cell therapy
- MeSH terms
- Anilides, Animals, Cartilage, Cartilage, Articular, Cell Differentiation, Cells, Cultured, Phthalic Acids, Regeneration, Synovial Fluid, Chondrogenesis, Rats, Exosomes, Mesenchymal Stem Cells
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