1.Establishment of Efficacy and Safety Assessment of Human Adipose Tissue-Derived Mesenchymal Stem Cells (hATMSCs) in a Nude Rat Femoral Segmental Defect Model.
Hyung Jun CHOI ; Jong Min KIM ; Euna KWON ; Jeong Hwan CHE ; Jae Il LEE ; Seong Ryul CHO ; Sung Keun KANG ; Jeong Chan RA ; Byeong Cheol KANG
Journal of Korean Medical Science 2011;26(4):482-491
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.
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