title: Establishment of efficacy and safety assessment of human adipose tissue-derived mesenchymal stem cells (hATMSCs) in a nude rat femoral segmental defect model.
abstract: Human adipose tissue-derived mesenchymal stem cell (hATMSC) have emerged as a potentially powerful tool for bone repair, but an appropriate evaluation system has not been established. The purpose of this study was to establish a preclinical assessment system to evaluate the efficacy and safety of cell therapies in a nude rat bone defect model. Segmental defects (5 mm) were created in the femoral diaphyses and transplanted with cell media (control), hydroxyapatite/tricalcium phosphate scaffolds (HA/TCP, Group I), hATMSCs (Group II), or three cell-loading density of hATMSC-loaded HA/TCP (Group III-V). Healing response was evaluated by serial radiography, micro-computed tomography and histology at 16 weeks. To address safety-concerns, we conducted a GLP-compliant toxicity study. Scanning electron microscopy studies showed that hATMSCs filled the pores/surfaces of scaffolds in a cell-loading density-dependent manner. We detected significant increases in bone formation in the hATMSC-loaded HA/TCP groups compared with other groups. The amount of new bone formation increased with increases in loaded cell number. In a toxicity study, no significant hATMSC-related changes were found in body weights, clinical signs, hematological/biochemical values, organ weights, or histopathological findings. In conclusion, hATMSCs loaded on HA/TCP enhance the repair of bone defects and was found to be safe under our preclinical efficacy/safety hybrid assessment system.
authors.affiliation: Graduate School of Immunology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyung Jun
authors.initials: HJ
authors.lastname: Choi
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Euna
authors.initials: E
authors.lastname: Kwon
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Che
authors.forename: Jae-Il
authors.initials: JI
authors.lastname: Lee
authors.forename: Seong-Ryul
authors.initials: SR
authors.lastname: Cho
authors.forename: Sung Keun
authors.initials: SK
authors.lastname: Kang
authors.forename: Jeong Chan
authors.initials: JC
authors.lastname: Ra
authors.forename: Byeong-Cheol
authors.initials: BC
authors.lastname: Kang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001672:Biocompatible Materials / Q000627:therapeutic use; D001847:Bone Diseases / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D001861:Bone Regeneration / Q000502:physiology; D002130:Calcium Phosphates / Q000627:therapeutic use; D018483:Diaphyses / Q000000981:diagnostic imaging / Q000601:surgery / Q000648:ultrastructure; D004195:Disease Models, Animal; D017886:Durapatite / Q000627:therapeutic use; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D011923:Rats, Nude; D023822:Tissue Engineering; D014057:Tomography, X-Ray Computed; D014183:Transplantation, Heterologous
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D017886:Durapatite; C018392:tricalcium phosphate