Establishment of Efficacy and Safety Assessment of Human Adipose Tissue-Derived Mesenchymal Stem Cells (hATMSCs) in a Nude Rat Femoral Segmental Defect Model.
10.3346/jkms.2011.26.4.482
- Author:
Hyung Jun CHOI
1
;
Jong Min KIM
;
Euna KWON
;
Jeong Hwan CHE
;
Jae Il LEE
;
Seong Ryul CHO
;
Sung Keun KANG
;
Jeong Chan RA
;
Byeong Cheol KANG
Author Information
1. Graduate School of Immunology, Seoul National University College of Medicine, Seoul, Korea. bckang@snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Safety;
Efficacy;
Human Adipose Tissue-Derived Mesenchymal Stem Cells;
HA/TCP Scaffold;
Bone Defect Model;
Nude Rats
- MeSH:
Adipose Tissue/*cytology;
Animals;
Biocompatible Materials/therapeutic use;
Bone Diseases/pathology/radiography/*therapy;
Bone Regeneration/physiology;
Calcium Phosphates/therapeutic use;
Diaphyses/radiography/surgery/ultrastructure;
Disease Models, Animal;
Durapatite/therapeutic use;
Femur/*pathology/radiography/surgery;
Humans;
Male;
*Mesenchymal Stem Cell Transplantation;
Mesenchymal Stem Cells/*cytology;
Rats;
Rats, Nude;
Tissue Engineering;
Tomography, X-Ray Computed;
Transplantation, Heterologous
- From:Journal of Korean Medical Science
2011;26(4):482-491
- CountryRepublic of Korea
- Language:English
-
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.
