Establishment of efficacy and safety assessment of human adipose tissue-derived mesenchymal stem cells (hATMSCs) in a nude rat femoral segmental defect model

• Published in: Journal of Korean medical science Vol. 26; no. 4; pp. 482 - 491
• Main Authors: Choi, Hyung Jun, Kim, Jong Min, Kwon, Euna, Che, Jeong-Hwan, Lee, Jae-Il, Cho, Seong-Ryul, Kang, Sung Keun, Ra, Jeong Chan, Kang, Byeong-Cheol
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Academy of Medical Sciences 01.04.2011; 대한의학회
• Subjects: Adipose Tissue - cytology; Animals; Biocompatible Materials - therapeutic use; Bone Diseases - diagnostic imaging; Bone Diseases - pathology; Bone Diseases - therapy; Bone Regeneration - physiology; Calcium Phosphates - therapeutic use; Diaphyses - diagnostic imaging; Diaphyses - surgery; Diaphyses - ultrastructure; Disease Models, Animal; Durapatite - therapeutic use; Femur - diagnostic imaging; Femur - pathology; Femur - surgery; Humans; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - cytology; Original; Rats; Rats, Nude; Tissue Engineering; Tomography, X-Ray Computed; Transplantation, Heterologous; 의학일반; Efficacy; Bone Defect Model; HA/TCP Scaffold; Nude Rats; Safety; Human Adipose Tissue-Derived Mesenchymal Stem Cells
• ISSN: 1011-8934; 1598-6357
• DOI: 10.3346/jkms.2011.26.4.482

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.