Autologous rabbit adipose tissue-derived mesenchymal stromal cells for the treatment of bone injuries with distraction osteogenesis

Background aims. Adipose tissue-derived mesenchymal stromal cells (MSCs) have a higher capacity for proliferation and differentiation compared with other cell lineages. Although distraction osteogenesis is the most important therapy for treating bone defects, this treatment is restricted in many situations. The aim of this study was to examine the therapeutic potential of adipose tissue-derived MSCs and osteoblasts differentiated from adipose tissue-derived MSCs in the treatment of bone defects. Methods. Bone defects were produced in the tibias of New Zealand rabbits that had previously undergone adipose tissue extraction. Tibial osteotomy was performed, and a distractor was placed on the right leg of the rabbits. The rabbits were placed in control (group I), stem cell (group II) and osteoblast-differentiated stem cell (group III) treatment groups. The rabbits were sacrificed, and the defect area was evaluated by radiologic, biomechanical and histopathologic tests to examine the therapeutic effects of adipose tissue-derived MSCs. Results. Radiologic analyses revealed that callus density and the ossification rate increased in group III compared with group I and group II. In biomechanical tests, the highest ossification rate was observed in group III. Histopathologic studies showed that the quality of newly formed bone and the number of cells active in bone formation were significantly higher in group III rabbits compared with group I and group II rabbits. Conclusions. These data reveal that osteoblasts differentiated from adipose tissue-derived MSCs shorten the consolidation period of distraction osteogenesis. Stem cells could be used as an effective treatment for bone defects

Are Endogenous BMPs Necessary for Bone Healing during Distraction Osteogenesis?

Previous reports suggest the application of exogenous BMPs can accelerate bone formation during distraction osteogenesis (DO). However, there are drawbacks associated with the use of exogenous BMPs. A possible alternative to the use of exogenous BMPs is to upregulate the expression of endogenous BMPs. Since DO results in spontaneously generated de novo bone formation in a uniform radiographic, histological, and biomechanical temporal sequence, a genetically engineered model lacking endogenous BMP2 should have measurable deficits in bone formation at different time points. We performed DO on BMP2 fl/+ and BMP2 fl/+ cre mice using a miniature Ilizarov fixator. Distracted samples were collected at various time points and analyzed using Real Time-quantitative PCR, μCT, radiology, immunohistochemistry, histology, and biomechanical testing. Immunohistochemical studies of 34-day heterozygous samples showed reduced expression of BMP2, BMP7, BMPR1a, ACTR1, and ACTR2b. μCT analysis of 51-day heterozygous samples revealed a decrease in trabecular number and increase in trabecular separation. Biomechanical testing of 51-day heterozygous samples revealed decreased stiffness and increased ultimate displacement. Radiological analysis showed the heterozygotes contained a decreased bone fill score at 17, 34, and 51 days. These data suggest endogenous BMPs are important for bone healing and manipulating endogenous BMPs may help accelerate bone consolidation during DO