Gene Therapy: A Review

2021 ◽  
Vol 8 (6) ◽  
pp. 35-39
Author(s):  
Shalya Raj ◽  
Rohit Ravinder ◽  
Preeti Mishra

The goal of gene-enhanced tissue engineering is to regenerate lost tissue by the local delivery of cells that have been genetically-enhanced to deliver physiologic levels of specific growth factors. The basis for this approach lies in the presence of a population of progenitor cells that can be induced, under the influence of these growth factors, to differentiate into the specific cells required for tissue regeneration, with guidance from local clues in the wound environment. Keywords: Gene therapy, Growth factor, Tissue engineering, Regeneration.

2021 ◽  
pp. 1-7
Author(s):  
Sarah Jarrin ◽  
Abrar Hakami ◽  
Ben Newland ◽  
Eilís Dowd

Despite decades of research and billions in global investment, there remains no preventative or curative treatment for any neurodegenerative condition, including Parkinson’s disease (PD). Arguably, the most promising approach for neuroprotection and neurorestoration in PD is using growth factors which can promote the growth and survival of degenerating neurons. However, although neurotrophin therapy may seem like the ideal approach for neurodegenerative disease, the use of growth factors as drugs presents major challenges because of their protein structure which creates serious hurdles related to accessing the brain and specific targeting of affected brain regions. To address these challenges, several different delivery systems have been developed, and two major approaches—direct infusion of the growth factor protein into the target brain region and in vivo gene therapy—have progressed to clinical trials in patients with PD. In addition to these clinically evaluated approaches, a range of other delivery methods are in various degrees of development, each with their own unique potential. This review will give a short overview of some of these alternative delivery systems, with a focus on ex vivo gene therapy and biomaterial-aided protein and gene delivery, and will provide some perspectives on their potential for clinical development and translation.


2002 ◽  
Vol 13 (5) ◽  
pp. 1-5 ◽  
Author(s):  
Mark H. Tuszynski ◽  
Hoi Sang U ◽  
John Alksne ◽  
Roy A. Bakay ◽  
Mary Margaret Pay ◽  
...  

The capacity to prevent neuronal degeneration and death during the course of progressive neurological disorders such as Alzheimer disease (AD) would represent a significant advance in therapy. Nervous system growth factors are families of naturally produced proteins that, in animal models, exhibit extensive potency in preventing neuronal death due to a variety of causes, reversing age-related atrophy of neurons, and ameliorating functional deficits. The main challenge in translating growth factor therapy to the clinic has been delivery of growth factors to the brain in sufficient concentrations to influence neuronal function. One means of achieving growth factor delivery to the central nervous system in a highly targeted, effective manner may be gene therapy. In this article the authors summarize the development and implementation of nerve growth factor gene delivery as a potential means of reducing cell loss in AD.


2021 ◽  
Vol 27 (8) ◽  
pp. 779-782
Author(s):  
Wei Shen ◽  
Xiaojun Liang

ABSTRACT Introduction: In recent years, genetic engineering has made outstanding contributions to sports, and it has played a huge role in promoting the development of sports-related fields. Objective: We analyze the tissue source of bone growth and healing by studying the role of bone morphogenetic protein and transforming growth factors in fracture injuries caused by sports. Methods: We established a human fracture model to express the shape and content of bone morphogenetic protein and transforming growth factor during fracture healing. Results: In the fracture healing stage caused by different sports, the expression levels of the two genes are different. Bone morphogenetic protein has a high content in the osteogenesis stage of the membrane, while transforming growth factor is high in the cartilage ossification stage. Conclusion: Gene therapy for fractures caused by physical exercise has certain advantages. Osteoblasts and chondrocytes are involved in the synthesis of transforming growth factors. Level of evidence II; Therapeutic studies - investigation of treatment results.


Author(s):  
E. Natsaridis ◽  
P. Mouzoura ◽  
F. Gkartziou ◽  
A. Marazioti ◽  
S.G. Antimisiaris

This review is an update about the efforts to develop liposomal carriers for growth factor delivery. It is well known that growth factors have the potential to enhance/accelerate tissue regeneration, however their poor stability which results in rapid loss of their activity, together with their rapid clearance from defected tissues (when applied as free molecules) is a serious drawback for their use; their highly hydrophilic nature and low capability to permeate through biological barriers (cell membranes) are additional factors that limit their applicability. In the last years, the advantages of liposomal drug delivery systems have motivated efforts to deliver growth factors (GFs) in liposomal form. Herein, after briefly introducing the basic structural characteristics of liposome types and their advantages when used as drug carriers, as well as the basic problems encountered when GFs are applied for tissue regeneration, we focus on recent reports about development and potential regenerative effects of liposomal GFs, towards defects of various tissues. The methodologies used for incorporation, attachment or immobilization of liposomal GFs in order to sustain their retention at the defected tissues, are highlighted as well.


2020 ◽  
Vol 6 (33) ◽  
pp. eabb5093 ◽  
Author(s):  
Fiona E. Freeman ◽  
Pierluca Pitacco ◽  
Lieke H. A. van Dommelen ◽  
Jessica Nulty ◽  
David C. Browe ◽  
...  

Therapeutic growth factor delivery typically requires supraphysiological dosages, which can cause undesirable off-target effects. The aim of this study was to 3D bioprint implants containing spatiotemporally defined patterns of growth factors optimized for coupled angiogenesis and osteogenesis. Using nanoparticle functionalized bioinks, it was possible to print implants with distinct growth factor patterns and release profiles spanning from days to weeks. The extent of angiogenesis in vivo depended on the spatial presentation of vascular endothelial growth factor (VEGF). Higher levels of vessel invasion were observed in implants containing a spatial gradient of VEGF compared to those homogenously loaded with the same total amount of protein. Printed implants containing a gradient of VEGF, coupled with spatially defined BMP-2 localization and release kinetics, accelerated large bone defect healing with little heterotopic bone formation. This demonstrates the potential of growth factor printing, a putative point of care therapy, for tightly controlled tissue regeneration.


2018 ◽  
Vol 59 (3-4) ◽  
pp. 265-275 ◽  
Author(s):  
Siegmund Lang ◽  
Markus Loibl ◽  
Marietta Herrmann

Background: Platelet-rich plasma (PRP) refers to an enriched platelet suspension in plasma. In addition to the clinical application of PRP in the context of various orthopedic diseases and beyond, PRP and platelet lysate (PL) have been in focus in the field of tissue engineering. In this review, we discuss the application of PRP as a cell culture supplement and as part of tissue engineering strategies, particularly emphasizing current hurdles and ambiguities regarding the efficacy of PRP in these approaches. Summary: As a putative autologous replacement for animal-derived supplements such as fetal calf serum (FCS), PRP has been applied as cell culture supplement for the expansion of stem and progenitor cells for tissue engineering applications and cell therapies. Attributed to the high content of growth factors in platelets, PRP has been shown to promote cell growth, which was mostly superior to standard cultures supplemented with FCS, while the differentiation capacity of progenitor cells seems not to be affected. However, it was also suggested that cultivation of cells with PRP significantly alters the protein expression profile in cells in comparison to FCS, indicating that the influence of PRP on cell behavior should be thoroughly investigated. Moreover, different PRP preparation methods and donor variations have to be considered for the use of PRP under good manufacturing practice conditions. PRP has been used for various tissue engineering applications in the context of bone, cartilage, skin, and soft tissue repair, where most studies were conducted in the field of bone tissue engineering. These approaches take either advantage of the release of chemoattractive, angiogenic, proliferative, and putatively pro-regenerative growth factors from PRP, and/or the hydrogel properties of activated PRP, making it suitable as a cell delivery vehicle. In many of these studies, PRP is combined with biomaterials, cells, and in some cases recombinant growth factors. Although the experimental design often does not allow conclusions on the pro-regenerative effect of PRP itself, most publications report beneficial effects if PRP is added to the tissue-engineered construct. Furthermore, it was demonstrated that the release of growth factors from PRP may be tailored and controlled when PRP is combined with materials able to capture growth factors. Key Messages: Platelet-derived preparations such as PRP and PL represent a promising source of autologous growth factors, which may be applied as cell culture supplement or to promote regeneration in tissue-engineered constructs. Furthermore, activated PRP is a promising candidate as an autologous cell carrier. However, the studies investigating PRP in these contexts often show conflicting results, which most likely can be attributed to the lack of standardized preparation methods, particularly with regard to the platelet content and donor variation of PRP. Ultimately, the use of PRP has to be tailored for the individual application.


Author(s):  
Christopher J. O’Conor ◽  
Kenneth W. Ng ◽  
Lindsay E. Kugler ◽  
Gerard A. Ateshian ◽  
Clark T. Hung

Agarose has been used as an experimental scaffold for cartilage tissue engineering research due to its biocompatibility with chondrocytes, support of cartilage tissue development, and ability to transmit mechanical stimuli [1–3]. Tissue engineering studies have demonstrated that the temporal application of transforming growth factor (TGF) β3 for only 2 weeks elicits rapid tissue development that results in mechanical properties approaching native values [4]. However, it is not known whether this response to a 2-week exposure to growth factors is unique to TGF-β3. Therefore, the present study characterizes the response of tissue engineered cartilage to the temporal application of the anabolic growth factors TGF-β1, TGF-β3, and insulin-like growth factor I (IGF-I).


RSC Advances ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 6735-6747
Author(s):  
Hong Shen ◽  
Xixue Hu

Cells, scaffolds and growth factors are three elements of tissue engineering. Growth factors precisely controlled by a scaffold will be used in conjunction with the scaffolds and cells to repair and regenerate defect tissue.


Author(s):  
Eunna Chung ◽  
Marissa Nichole Rylander

Tissue engineering is an emerging field that focuses on development of methods for repairing and regenerating damaged or diseased tissue. Successful development of engineered tissues is often limited by insufficient cellular proliferation and insufficient formation of extracellular matrix. To induce effective bone regeneration, many research groups have investigated the cellular response and capability for tissue regeneration associated with bioreactor conditions and addition of growth factors [1]. Bioreactors in tissue engineering have been developed to expose cells to a similar stress environment as found within the body or induce elevated stress levels for potential induction of specific cellular responses associated with tissue regeneration. Native bone encounters a diverse array of dynamic stresses such as shear, tensile, and compression daily. Stress conditioning protocols in the form of thermal or tensile stress have been shown to induce up-regulation of molecular chaperones called heat shock proteins (HSPs) and bone-related proteins like MMP13 (matrix metallopeptidase 13) [2] and OPG (osteoprotegerin) [3, 4]. HSPs have important roles in enhancing cell proliferation and collagen synthesis. Osteogenic growth factors such as TGF-β1 (transforming growth factor beta 1) and BMP-2 (bone morphogenetic protein 2) are related to bone remodeling and osteogenesis as well as HSP induction [5]. Therefore, identification of effective preconditioning using growth factors and stress protocols that enhance HSP expression could substantially advance development of bone regeneration. The purpose of this research was to identify preconditioning protocols using osteogenic growth factors and tensile stress applied through a bioreactor system to enhance expression of HSPs and bone-related proteins while minimizing cellular injury for ultimate use for bone regeneration.


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