title: In vivo tracking of mesechymal stem cells using fluorescent nanoparticles in an osteochondral repair model.
abstract: We devised and tested an in vivo system to monitor the migration of mesenchymal stem cells (MSCs) within the marrow cavity. In vitro studies confirmed that platelet-derived growth factor (PDGF)-AA had the most potent chemotactic effect of the tested factors, and possessed the greatest number of receptors in MSCs. MSCs were labeled with fluorescent nanoparticles and injected into the marrow cavity of nude rats through osteochondral defects created in the distal femur. The defects were sealed with HCF (heparin-conjugated fibrin) or PDGF-AA-loaded HCF. In the HCF-only group, the nanoparticle-labeled MSCs dispersed outside the marrow cavity within 3 days after injection. In the PDGF-AA-loaded HCF group, the labeled cells moved time-dependently for 14 days toward the osteochondral defect. HCF-PDGF in low dose (LD; 8.5 ng/µl) was more effective than HCF-PDGF in high dose (HD; 17 ng/µl) in recruiting the MSCs to the osteochondral defect. After 21 days, the defects treated with PDGF and transforming growth factor (TGF)-β1-loaded HCF showed excellent cartilage repair compared with other groups. Further studies confirmed that this in vivo osteochondral MSCs tracking system (IOMTS) worked for other chemoattractants (chemokine (C-C motif) ligand 2 (CCL2) and PDGF-BB). IOMTS can provide a useful tool to examine the effect of growth factors or chemokines on endogenous cartilage repair.
authors.affiliation: Department of Orthopaedics, Dongguk University Ilsan Hospital, Goyang, Korea.
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
authors.forename: Haeshin
authors.initials: H
authors.lastname: Lee
authors.forename: Gun-Il
authors.initials: GI
authors.lastname: Im
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002358:Cartilage, Articular / Q000502:physiology*; D002465:Cell Movement; D018932:Chemokine CCL2; D018925:Chemokines / Q000378:metabolism; D002630:Chemotactic Factors / Q000378:metabolism; D005456:Fluorescent Dyes; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D053758:Nanoparticles; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051381:Rats; D011923:Rats, Nude; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D012038:Regeneration; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D018925:Chemokines; D002630:Chemotactic Factors; D005456:Fluorescent Dyes; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor