Gene-augmented mesenchymal stem cells in bone repair
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The Ohio State University / OhioLINK
2006
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=osu1146076285 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu11460762852021-08-03T05:50:47Z Gene-augmented mesenchymal stem cells in bone repair Zachos, Terri A. Adenoviral gene delivery Gene therapy Bone morphogenetic proteins Growth factors Nonunion Articular fractures Bone healing Rodent models Complicated healing of articular fractures represents a clinical challenge and a financial burden on the health care system. Bone marrow-derived mesenchymal stem cells (BMDMSC) hold promise for targeted osteogenic differentiation and can be augmented by delivery of genes encoding bone morphogenetic proteins (BMP). Osteogenic differentiation of BMDMSC was investigated using two BMP genes. Cultured BMDMSC were transduced with adenoviral vectors containing human BMP2 or BMP6 in either sustained in monolayer or suspended in alginate for 22 days. Adenovirus (Ad)-BMP-2 and Ad-BMP-6 transduction resulted in abundant BMP-2 and BMP-6 mRNA and ligand expression in monolayer culture and BMP-2 ligand expression in alginate. Ad-BMP-2 and Ad-BMP-6 transduced BMDMSC in monolayer had earlier alkaline phosphatase-positive staining and mineralization and were sustained for a longer duration than untransduced or Ad-ß-galactosidase-transduced cells. Gene expression studies at day 2 confirmed an inflammatory response to the gene delivery process. Up-regulation of genes consistent with response to BMP exposure and osteogenic differentiation occurred in BMP-transduced cells. These data support that transduction of BMDMSC with Ad-BMP-2 or Ad-BMP-6 can accelerate osteogenic differentiation and mineralization of stem cells. BMP-2-transduced stem cells suspended in alginate culture may be a practical carrier system to support bone formation in vivo. A distal femoral articular osteotomy model was created in the nude rat to study articular fracture healing. Osteotomies were treated with BMDMSC, wild-type (NoAd) or transduced with Ad-BMP-2. Cells were delivered in alginate (ALG) or injected in saline. Controls were empty ALG, saline injections, direct Ad-BMP-2 injection, and untreated osteotomies. Healing was compared using quantitative micro-computed tomography, fluorescent labeling, and histology. At day 14, osteotomy gap area in the Ad-BMP-2 ALG group was significantly greater than other groups (P < 0.0003). The group treated with Ad-BMP2-transduced cells injected in saline (Ad-BMP-2 cells) healed with less osteotomy gap area (P < 0.0001) and volume (P < 0.02) than untreated controls. In ALG groups, bone healing was impeded by development of a chondroid mass most pronounced in the Ad-BMP-2 ALG group. Injection of Ad-BMP2-transduced BMDMSC in saline accelerated bone healing and reconstituted the articular surface in this distal femoral osteotomy model of articular fracture healing. 2006-07-14 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1146076285 http://rave.ohiolink.edu/etdc/view?acc_num=osu1146076285 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Adenoviral gene delivery Gene therapy Bone morphogenetic proteins Growth factors Nonunion Articular fractures Bone healing Rodent models |
| spellingShingle |
Adenoviral gene delivery Gene therapy Bone morphogenetic proteins Growth factors Nonunion Articular fractures Bone healing Rodent models Zachos, Terri A. Gene-augmented mesenchymal stem cells in bone repair |
| author |
Zachos, Terri A. |
| author_facet |
Zachos, Terri A. |
| author_sort |
Zachos, Terri A. |
| title |
Gene-augmented mesenchymal stem cells in bone repair |
| title_short |
Gene-augmented mesenchymal stem cells in bone repair |
| title_full |
Gene-augmented mesenchymal stem cells in bone repair |
| title_fullStr |
Gene-augmented mesenchymal stem cells in bone repair |
| title_full_unstemmed |
Gene-augmented mesenchymal stem cells in bone repair |
| title_sort |
gene-augmented mesenchymal stem cells in bone repair |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2006 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1146076285 |
| work_keys_str_mv |
AT zachosterria geneaugmentedmesenchymalstemcellsinbonerepair |
| _version_ |
1719426509852114944 |