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

Xu，Xiao1,2; Liang，Yujie1,3; Li，Xingfu1; Ouyang，Kan1; Wang，Manyi1; Cao，Tong5; Li，Wencui1; Liu，Jianquan1; Xiong，Jianyi1; Li，Biquan3; Xia，Jiang3,4; Wang，Daping1,2,6; Duan，Li1

2021-02-01

10.1016/j.biomaterials.2020.120539

BIOMATERIALS   影响因子和分区

0142-9612

1878-5905

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.

Exosome Synovial fluid-mesenchymal stem cells Osteoarthritis Kartogenin Chondrogenic differentiation

EI ; SCI

英语

ESI高被引

其他

National Natural Science Foundation of China[81772394,81972116,81972085] ; Key Program of Natural Science Foundation of Guangdong Province[2018B0303110003] ; China postdoctoral science foundation[2020M682907] ; Shenzhen Fund for Guangdong Provincial High level Clinical Key Specialties["SZGSP007","SZSM201412015"] ; Shenzhen Science and Technology Projects["KQTD20170331100838136","JCYJ20170817172023838","JCYJ20170306092215436","JCYJ2017041 2150609690","JCYJ20170413161649437","JCYJ20170413161800287","SGLH20161209105517753"] ; Shenzhen Key Medical Discipline Construction Fund[SZXK049] ; Special Funds for the Construction of High-level Hospitals in Guangdong Province[4001013] ; National Key R&D Program of China[2018YFA0903204] ; University Grants Committee of Hong Kong[14306317,"N_CUHK422/18",14307218,"AoE/M-09/12"]

Engineering ; Materials Science

Engineering, Biomedical ; Materials Science, Biomaterials

WOS:000617951100001

ELSEVIER SCI LTD

20204909585390

Joints (anatomy) ; Stem cells ; Peptides ; Cell culture ; Flowcharting

Biological Materials and Tissue Engineering:461.2 ; Biomechanics, Bionics and Biomimetics:461.3 ; Biology:461.9 ; Computer Programming:723.1

MATERIALS SCIENCE

Web of Science

1.Department of Orthopedics,Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform,Guangdong Artificial Intelligence Biomedical Innovation Platform,Shenzhen Second People's Hospital,The First Affiliated Hospital of Shenzhen University Health Science Center,Shenzhen,518035,China
2.Guangzhou Medical University,Guangzhou,511436,China
3.Department of Chemistry,China
4.Center for Cell & Developmental Biology,School of Life Sciences,The Chinese University of Hong Kong,Shatin,Hong Kong
5.Faculty of Dentistry,National University of Singapore,China
6.Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,518055,China

Xu，Xiao,Liang，Yujie,Li，Xingfu,et al. Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration[J]. BIOMATERIALS,2021,269.

Xu，Xiao.,Liang，Yujie.,Li，Xingfu.,Ouyang，Kan.,Wang，Manyi.,...&Duan，Li.(2021).Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration.BIOMATERIALS,269.

Xu，Xiao,et al."Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration".BIOMATERIALS 269(2021).