Cited by 377Osteoarthritis Treatment and MechanismsExtracellular vesicles in diseaseMesenchymal stem cell research

Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration

Xu, Xiao, Liang, Yujie, Li, Xingfu, Ouyang, Kan, Wang, Manyi, Cao, Tong, Li, Wencui, Liu, Jianquan +5 more·2021·Biomaterials

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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Crossref · 10.1016/j.biomaterials.2020.120539

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  • Exosomes can be genetically engineered, chemically surface modified or enzymatically engineered to introduce peptides and proteins to enhance their targeting ability.

    “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].”
  • In a rat model, KGN loaded by engineered exosomes showed better therapeutic effects than KGN alone.

    “In a rat model, KGN loaded by engineered exosomes also showed better therapeutic effects than KGN alone [89].”
  • Targeting KGN to 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.

    “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.”

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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 · 2020: 1
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
  • Health Sciences › Medicine › Genetics › 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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