The Role of Gene Therapy in Regenerative Surgery: Updated Insights
ABSTRACT BACKGROUND:: In the past two decades, regenerative surgeons have focused increasing attention on the potential of gene therapy for treatment of local disorders and injuries. Gene transfer techniques may provide an effective local and short-term induction of growth factors without the limits of other topical therapies. In 2002, Tepper and Mehrara accurately reviewed the topic: given the substantial advancement of research on this issue, an updated review is provided. METHODS:: Literature indexed in the National Center for Biotechnology Information database (PubMed) has been reviewed using variable combinations of keywords ("gene therapy," "regenerative medicine," "tissue regeneration," and "gene medicine"). Articles investigating the association between gene therapies and local pathologic conditions have been considered. Attention has been focused on articles published after 2002. Further literature has been obtained by analysis of references listed in reviewed articles. RESULTS:: Gene therapy approaches have been successfully adopted in preclinical models for treatment of a large variety of local diseases affecting almost every type of tissue. Experiences in abnormalities involving skin (e.g., chronic wounds, burn injuries, pathologic scars), bone, cartilage, endothelia, and nerves have been reviewed. In addition, the supporting role of gene therapies to other tissue-engineering approaches has been discussed. Despite initial reports, clinical evidence has been provided only for treatment of diabetic ulcers, rheumatoid arthritis, and osteoarthritis. CONCLUSIONS:: Translation of gene therapy strategies into human clinical trials is still a lengthy, difficult, and expensive process. Even so, cutting-edge gene therapy-based strategies in reconstructive procedures could soon set valuable milestones for development of efficient treatments in a growing number of local diseases and injuries.
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ABSTRACT: Introduction: There are safety concerns regarding viral vectors in regenerative medicine research because of adverse experiences in conventional gene therapy with systemic delivery of recombinant virus. Transgenic cell therapy emerges as an attractive strategy, in which the genes of interest are delivered in vitro into isolated cells first; instead of transgene vectors, these transgenic cells are then implanted back to the host. This ex vivo strategy enables the examination of cell viability and phenotype before subsequent transplantation and prevents to the most extent the potential delivery-related hazards caused by exposure of viral components to the host. The transgenic implants are often localized, thus traceable for safety monitoring except those cases involving systemic distribution of transgenic cells.Areas covered: The safety of ex vivo process used in viral vector-mediated transgenic cell therapy for regenerative medicine purpose.Expert opinion: Safety concerns related to viral vector delivery can be dispelled in the majority of regenerative medicine applications by transgenic cell therapy. The ex vivo process executes in vitro transfection before subsequent transplantation of transgenic cells so that it avoids the exposure of viral components (particularly capsids or envelops) to the host, while this exposure is inevitable in conventional in vivo gene therapy. Besides, the practice of localized cell implantation and in vitro manipulation also reinforce the safety of transgenic cell therapy. Given the significantly reduced delivery-related hazard, viral vector-mediated transgenic cell therapy can be generally considered as a safe approach for most regenerative medicine applications.Expert Opinion on Biological Therapy 12/2014; 15(4). DOI:10.1517/14712598.2015.995086 · 3.65 Impact Factor
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ABSTRACT: Introduction: Currently, joint arthroplasty remains the only definitive management of osteoarthritis, while other treatment modalities only provide temporary and symptomatic relief. The use of genetically engineered chondrocytes is currently undergoing clinical trials. Specifically, it has been designed to induce cartilage growth and differentiation in patients with degenerative arthritis, with the aim to play a curative role in the disease process. Areas covered: This treatment involves the incorporation of TGF-β1, which has been determined to play an influential role in chondrogenesis and extracellular matrix synthesis. Using genetic manipulation and viral transduction, TGF-β1 is incorporated into human chondrocytes and administered in a minimally invasive fashion directly to the affected joint. Following a database literature search, we evaluated the current evidence on this product and its outcomes. Furthermore, we also briefly reviewed other treatments developed for chondrogenesis and cartilage regeneration for comparison. Expert opinion: This treatment method has sustained positive effects on functional outcomes and cartilage growth in initial trials. It allows administration in a minimally invasive manner that does not require extended recovery time. Although several treatment modalities are currently under investigation and appear promising, we hope that these effects can be sustained in further studies. Ultimately, we anticipate that the results may be reproducible in many clinical settings and allow us to effectively treat cartilage damage in patients with degenerative arthritis.Expert Opinion on Biological Therapy 02/2015; 15(3):1-10. DOI:10.1517/14712598.2015.1009886 · 3.65 Impact Factor
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ABSTRACT: Non-viral gene delivery systems are important transport vehicles that can be safe and effective alternatives to currently available viral systems. A new family of multifunctional spider silk-based gene carriers was bioengineered and found capable of targeting human mesenchymal stem cells (hMSCs). These carriers successfully delivered DNA to the nucleus of these mammalian cells. The presence of specific functional sequences in the recombinant proteins, such as a nuclear localization sequence (NLS) of the large tumor (T) antigen of the Simian virus 40 (SV40), an hMSC high affinity binding peptide (HAB), and a translocation motif (TLM) of the hepatitis-B virus surface protein (PreS2), and their roles in mitigation and enhancement of gene transfection efficiency towards hMSCs were characterized. The results demonstrate that these bioengineered spider silk proteins serve as effective carriers, without the well-known complications associated with viral delivery systems. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2014.Journal of Biomedical Materials Research Part B Applied Biomaterials 12/2014; DOI:10.1002/jbm.b.33322 · 2.33 Impact Factor