Publications by authors named "A Atasoy-Zeybek"

3 Publications

  • Page 1 of 1

Gene therapy for bone healing: lessons learned and new approaches.

Transl Res 2021 May 5. Epub 2021 May 5.

Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, Minnesota; Musculoskeletal Gene Therapy Research Laboratory, Mayo Clinic, Rochester, Minnesota; IBE, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands.

Although gene therapy has its conceptual origins in the treatment of Mendelian disorders, it has potential applications in regenerative medicine, including bone healing. Research into the use of gene therapy for bone healing began in the 1990s. Prior to this period, the highly osteogenic proteins bone morphogenetic protein (BMP)-2 and -7 were cloned, produced in their recombinant forms and approved for clinical use. Despite their promising osteogenic properties, the clinical usefulness of recombinant BMPs is hindered by delivery problems that necessitate their application in vastly supraphysiological amounts. This generates adverse side effects, some of them severe, and raises costs; moreover, the clinical efficacy of the recombinant proteins is modest. Gene delivery offers a potential strategy for overcoming these limitations. Our research has focused on delivering a cDNA encoding human BMP-2, because the recombinant protein is Food and Drug Administration approved and there is a large body of data on its effects in people with broken bones. However, there is also a sizeable literature describing experimental results obtained with other transgenes that may directly or indirectly promote bone formation. Data from experiments in small animal models confirm that intralesional delivery of BMP-2 cDNA is able to heal defects efficiently and safely while generating transient, local BMP-2 concentrations 2-3 log orders less than those needed by recombinant BMP-2. The next challenge is to translate this information into a clinically expedient technology for bone healing. Our present research focuses on the use of genetically modified, allografted cells and chemically modified messenger RNA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.trsl.2021.04.009DOI Listing
May 2021

Paracrine effects of living human bone particles on the osteogenic differentiation of mesenchymal stem cells.

Eur Cell Mater 2019 07 23;38:14-22. Epub 2019 Jul 23.

Rehabilitation Medicine Research Centre, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905,

Bone autografting remains the clinical model of choice for resolving problematic fractures. The precise mechanisms through which the autograft promotes bone healing are unknown. The present study examined the hypothesis that cells within the autograft secrete osteogenic factors promoting the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. Particles of human bone ("chips") were recovered at the time of joint replacement surgery and placed in culture. Then, conditioned media were added to cultures of human, adipose-derived MSCs under both basal and osteogenic conditions. Contrary to expectation, medium conditioned by bone chips reduced the expression of alkaline phosphatase and strongly inhibited mineral deposition by MSCs cultured in osteogenic medium. Real time PCR revealed the inhibition of collagen type I alpha 1 chain (Col1A1) and osteopontin (OPN) expression. These data indicated that the factors secreted by bone chips inhibited the osteogenic differentiation of MSCs. However, in late cultures, bone morphogenetic protein-2 (BMP-2) expression was stimulated, suggesting the possibility of a delayed, secondary osteogenic effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22203/eCM.v038a02DOI Listing
July 2019

Gene Therapy Strategies in Bone Tissue Engineering and Current Clinical Applications.

Adv Exp Med Biol 2018;1119:85-101

Faculty of Engineering, Genetics and Bioengineering Department, Yeditepe University, Istanbul, Turkey.

Gene therapy provides a promising approach for regeneration and repair of injured bone. Application of gene therapy has displayed increased efficiency in various animal models and preclinical trials in comparison with traditional bone grafting methods. The objective of this review is to highlight fundamental principles of gene therapy strategies in bone tissue engineering and solutions of their current limitations for the healing of bone injury. Vector types are debated for the repair of defected site due to demonstration of constraints and applications of the protocols. In recent years, the combination of gene therapy strategies and bone tissue engineering has highly gained attention. We discussed viral and non-viral mediated delivery of therapeutic protein by using scaffolds for bone tissue engineering. Although pre-clinical studies have showed that gene therapy has very promising results to heal injured bone, there are several limitations regarding with the usage of gene delivery methods into clinical applications. Choice of suitable vector, selection of transgene and gene delivery protocols are the most outstanding questions. This article also addresses current state of gene delivery strategies in bone tissue engineering for their potential applications in clinical considerations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/5584_2018_253DOI Listing
July 2019