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

J Korean Med Sci. 2011 Apr;26(4):482-91. doi: 10.3346/jkms.2011.26.4.482. Epub 2011 Mar 28.


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.

Keywords: Bone Defect Model; Efficacy; HA/TCP Scaffold; Human Adipose Tissue-Derived Mesenchymal Stem Cells; Nude Rats; Safety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 Stem Cells / cytology*
  • Rats
  • Rats, Nude
  • Tissue Engineering
  • Tomography, X-Ray Computed
  • Transplantation, Heterologous


  • Biocompatible Materials
  • Calcium Phosphates
  • Durapatite
  • tricalcium phosphate