Osteoinduction by Ex Vivo Nonviral Bone Morphogenetic Protein Gene Delivery Is Independent of Cell Type

Tissue Engineering. Part a
Loek D LoozenJacqueline Alblas

Abstract

Ex vivo nonviral gene delivery of bone inductive factors has the potential to heal bone defects. Due to their inherent role in new bone formation, multipotent stromal cells (MSCs) have been studied as the primary target cell for gene delivery in a preclinical setting. The relative contribution of autocrine and paracrine mechanisms, and the need of osteogenic cells, remains unclear. This study investigates the contribution of MSCs as producer of transgenic bone morphogenetic proteins (BMPs) and to what extent the seeded MSCs participate in actual osteogenesis. Rat-derived MSCs or fibroblasts (FBs) were cotransfected with pBMP-2 and pBMP-6 or pBMP-7 via nucleofection. The bioactivity of BMP products was shown through in vitro osteogenic differentiation assays. To investigate their role in new bone formation, transfected cells were seeded on ceramic scaffolds and implanted subcutaneously in rats. Bone formation was assessed by histomorphometry after 8 weeks. As a proof of principle, we also investigated the suitability of bone marrow-derived mononuclear cells and the stromal vascular fraction isolated from adipose tissue for a one-stage gene delivery strategy. Bone formation was induced in all conditions containing cells overexpre...Continue Reading

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Citations

Aug 8, 2019·Pharmaceutics·Shin-Young ParkYang-Jo Seol
Oct 13, 2020·Frontiers in Bioengineering and Biotechnology·Li WangHongyan Guo
May 25, 2020·Bone·Maxim BezDan Gazit

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Methods Mentioned

BETA
transfection
transgenic
transfecting
fluorescence microscopy

Software Mentioned

SPSS

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