Mesenchymal Stem Cell-mediated Gene Delivery of Bone Morphogenetic Protein-2 in an Articular Fracture Model

Abstract

In articular fractures, both bone and cartilage are injured. We tested whether stem cells transduced with bone morphogenetic protein 2 (BMP2) can promote bone and cartilage repair. Distal femoral articular osteotomies in nude rats were treated with stem cells, either wild-type or transduced with an adenoviral (Ad) BMP2. Cells were delivered in alginate (ALG) carrier or by direct injection in saline solution. Gene expression of these cells at the osteotomy site was confirmed by in vivo imaging. At day 14, only the group that received AdBMP2 stem cells by direct injection showed completely healed osteotomies, while other groups remained unhealed (P < 0.0003). In ALG groups, bone healing was impeded by the development of a chondroid mass, most pronounced in the AdBMP2 ALG group (P < 0.002). We were successful in achieving repair of both bone and cartilage in vivousing direct stem cell injection. Our data suggests that BMP2 augmentation might be critically important in achieving this effect.

A Rat Model of Chondrocyte Death After Closed Intra-Articular Fracture

“…Proposed models have included drilling holes in an exposed joint surface, 16 open osteotomies, 17,18 impacting articular cartilage with no fracture, and impacting cartilage samples ex vivo. 19,20 These require open dissection of the joint and do not create true fractures, exposing the chondrocytes to very different physiologic and mechanical environments than they would normally experience in a clinical fracture.…”

EnhancedIn VitroChondrogenesis of Primary Mesenchymal Stem Cells by Combined Gene Transfer

“…Because IGF-1, 36,37 BMP-2, 36,48 and TGF-b1 38 have each been used successfully in animal models of tissue repair, the purpose of the present study was to explore methods to enhance MSCs were transduced with 2.5Â10 2 vp=cell of the respective adenoviral vectors as indicated, seeded into aggregates, and maintained in a defined serum-free medium for 3, 7, or 14 days. For each treatment group and time point indicated, RNA was extracted from 10 aggregates per marrow preparation, and expression of cartilage-specific marker genes was determined according to reverse transcriptase polymerase chain reaction (RT-PCR) from three different marrow preparations (m ¼ 3).…”

Quantifying mechanical properties in a murine fracture healing system using inverse modeling: preliminary work

“…In addition, there is an equally important need to understand how to therapeutically promote better and more mechanically stable fracture healing. As a result, many researchers are studying fracture healing animal models within the context of treatment therapeutics [2][3][4][5][6][7][8]. While a great deal of work has been targeted at assessment of healing via imaging methods [9][10][11][12][13][14][15][16], there is real need to monitor and characterize the load-bearing mechanical properties of an experimental fracture callus system in response therapeutic intervention.…”