Biodegradable Plga-Adipose Derived Stem Cells Carrier System Used for Femoral Bone Healing and Posterolateral Spine Fusion in the Rabbit Model

  • Fu, Tsai-Sheng (PI)
  • Chang, Yu-Han (CoPI)
  • Chen, Wen-Jer (CoPI)
  • Chen, Lih-Huei (CoPI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

In our previous studies, we proved that low dose bone morphogenetic protein-2 (BMP-2) could enhance bone marrow mesenchymal stem cells (BMSCs) to achieve successful spinal posterolateral fusion in rabbit model. Over the past three decades, BMSCs have been used as a popular cell source for regenerative medicine research. However, the isolation of BMSCs frequently yields a low number of stem cells and the isolation procedure is invasive for donors or patients. In contrast, adipose tissue has recently been identified as one of the alternative sources of multipotent resident stem cells. Adipose derived mesenchymal stem cells (ADSCs) have also been established with the multipotency of differentiation into not only mesenchymal lineage cells such as osteoblasts, chondrocytes, myocytes, cardiomyocytes, fibroblasts and adipocytes but also vascular lineage cells. ADSCs isolated from young donors show fast adherent cell characteristics in culture and have more extensive expansion capacity. In the preliminary results of our 2011 NMRP project, the ADSCs had been successfully isolated from rabbits and cultured in special medium for differentiating into osteogenic lineage cells. In this 2-year study, we plan to keep on further related studies based on our previous results. we hypothesis that ADSCs combined with tissue engineering technique could have osteogenetic ability and therapeutic potential for bone growth and fracture healing through direct contribution to tissue regeneration by differentiating into osteogenic lineage cells. We use New Zealand White (NZW) rabbits as an animal model. The ADSCs will be isolated from rabbits and cultured in special medium for differentiating into osteogenic lineage cells and will seeded into 3D PLGA scaffolds. In the 1st year, the cells/scaffold constructs will be implanted into NZW rabbits (femoral critical bone defect). We will compare the successful rate of the autogenous iliac bone graft, PLGA only, BMSCs/PLGA construct, and ADSCs/PLGA constructs for femoral critical defect bone healing. In the 2nd year, the cells/scaffold constructs will be implanted into NZW rabbits (L4-5 intertransverse space) to define the ability of ADSCs for repairing large defect. We will compare the successful rate of the autogenous iliac bone graft, PLGA only, BMSCs/PLGA construct, and ADSCs/PLGA constructs for posterolateral spine fusion. The bone formation and healing conditions of femoral and L4-5 posterolateral fusion will be determined by radiographic examination (plain X-ray and CT), manual palpation, histological examination and biomechanical test. The blood vessel formation will also be checked by histochemical staining at the end point of the experiment. The results of these studies may provide an effectively biological approach to enhance bone growth and fracture healing. In the future, these methods may be applicable on the clinical service.

Project IDs

Project ID:PC10108-1123
External Project ID:NSC101-2314-B182-089
StatusFinished
Effective start/end date01/08/1231/07/13

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