Nonviral gene transfer strategies to promote bone regeneration

Im, Gun‐Il

doi:10.1002/jbm.a.34576

Cited by 12 publications

(8 citation statements)

References 127 publications

(263 reference statements)

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“…Owing to advancements in molecular and physiological sciences, there is a growing understanding of the cellular events and underlying mechanisms involved in healthy fracture healing and natural bone regeneration . However, in spite of bone's natural ability to regenerate following an injury, large amounts of bone loss due to trauma, tumor excision, developmental anomalies, or infections do not heal on their own and require therapeutic intervention (Fig. B ).…”

Section: Introductionmentioning

confidence: 99%

Small Players Ruling the Hard Game: siRNA in Bone Regeneration

Ghadakzadeh

Mekhail

Aoude

et al. 2016

Journal of Bone and Mineral Research

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Silencing gene expression through a sequence-specific manner can be achieved by small interfering RNAs (siRNAs). The discovery of this process has opened the doors to the development of siRNA therapeutics. Although several preclinical and clinical studies have shown great promise in the treatment of neurological disorders, cancers, dominant disorders, and viral infections with siRNA, siRNA therapy is still gaining ground in musculoskeletal tissue repair and bone regeneration. Here we present a comprehensive review of the literature to summarize different siRNA delivery strategies utilized to enhance bone regeneration. With advancement in understanding the targetable biological pathways involved in bone regeneration and also the rapid progress in siRNA technologies, application of siRNA for bone regeneration has great therapeutic potential. High rates of musculoskeletal injuries and diseases, and their inevitable consequences, impose a huge financial burden on individuals and healthcare systems worldwide.

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Section: Introductionmentioning

confidence: 99%

Small Players Ruling the Hard Game: siRNA in Bone Regeneration

Ghadakzadeh

Mekhail

Aoude

et al. 2016

Journal of Bone and Mineral Research

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“…Therefore, it would be important in follow up research to investigate if MSCs from various tissues sources can be tenogenically committed by Scx overexpression in a non-viral, transient manner. Several papers have already discussed non-viral based gene transfer strategies for enhancing musculoskeletal engineering and healing [33,34,35]. One drawback of this study, namely donor matching in gender and age, should also be addressed in future investigations.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Comparison of 2D-Cell Culture and 3D-Cell Sheets of Scleraxis-Programmed Bone Marrow Derived Mesenchymal Stem Cells to Primary Tendon Stem/Progenitor Cells for Tendon Repair

Hsieh

Zhi-yong

Schumann

et al. 2018

IJMS

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The poor and slow healing capacity of tendons requires novel strategies to speed up the tendon repair process. Hence, new and promising developments in tendon tissue engineering have become increasingly relevant. Previously, we have established a tendon progenitor cell line via ectopic expression of the tendon-related basic helix-loop-helix (bHLH) transcription factor Scleraxis (Scx) in human bone marrow mesenchymal stem cells (hMSC-Scx). The aim of this study was to directly compare the characteristics of hMSC-Scx cells to that of primary human tendon stem/progenitors cells (hTSPCs) via assessment of self-renewal and multipotency, gene marker expression profiling, in vitro wound healing assay and three-dimensional cell sheet formation. As expected, hTSPCs were more naive than hMSC-Scx cells because of higher clonogenicity, trilineage differentiation potential, and expression of stem cell markers, as well as higher mRNA levels of several gene factors associated with early tendon development. Interestingly, with regards to wound healing, both cell types demonstrate a comparable speed of scratch closure, as well as migratory velocity and distance in various migration experiments. In the three-dimensional cell sheet model, hMSC-Scx cells and hTSPCs form compact tendinous sheets as histological staining, and transmission electron microscopy shows spindle-shaped cells and collagen type I fibrils with similar average diameter size and distribution. Taken together, hTSPCs exceed hMSC-Scx cells in several characteristics, namely clonogenicity, multipotentiality, gene expression profile and rates of tendon-like sheet formation, whilst in three-dimensional cell sheets, both cell types have comparable in vitro healing potential and collagenous composition of their three-dimensional cell sheets, making both cell types a suitable cell source for tendon tissue engineering and healing.

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“…16 Compared with viral vectors, nonviral gene vectors are less immunogenic and are not integrated into the host's genome, so insertional mutagenesis is avoided. [21][22][23] The results of the luciferase tests proved that the genes are expressed in a time-limited manner, which is desirable because of the severe side effects of uncontrolled tissue proliferation during regenerative processes, such as bone healing. 24 Therefore, this method was used in this study.…”

Section: Discussionmentioning

confidence: 99%

Functional analysis of bioactivated and antiinfective PDLLA – coated surfaces

Haidari

Boskov

Schillinger

et al. 2017

J Biomedical Materials Res

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Common scaffold surfaces such as titanium can have side effects; for example, infections, cytotoxicity, impaired osseointegration, or low regeneration rates for bone tissue. These effects lead to poor implant integration or even implant loss. Therefore, bioactive implants are promising instruments in tissue regeneration. Osteoinductive elements-such as growth factors and anti-infectives-support wound healing and bone growth and thereby enable faster osseointegration, even in elderly patients. In this study, titanium surfaces were coated with a poly-(d,l-lactide) (PDLLA) layer containing different concentrations of copolymer-protected gene vectors (COPROGs) to locally provide bone morphogenetic protein-2 (BMP-2) or activated anti-infective agents, such as chlorhexidine gluconate, triclosan, and metronidazole, to prevent peri-implantitis. The coated titanium implants were then loaded with osteoblasts, NIH 3T3 fibroblasts, and human mesenchymal stem cells in 96-well plates. When shielded by COPROGs as a protective layer and resuspended in PDLLA, BMP-2-encoding pDNA at relatively low doses (5.63 µg/implant) induced the local expression of BMP-2. A linear dose dependence, which is common for recombinant growth factors, was not found, probably due to the retention property of the PDLLA surface. PDLLA, in general, successfully retains additional elements, such as osteoconductive growth factors (BMP-2) and anti-infective agents, which was demonstrated using metronidazole, and thus prevents the systemic application of excessive doses. These bioactive implant surfaces that provide the local release of therapeutic gene vectors or anti-infective agents allow the controlled stimulation of the implant and scaffold osseointegration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1672-1683, 2017.

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Nonviral gene transfer strategies to promote bone regeneration

Cited by 12 publications

References 127 publications

Small Players Ruling the Hard Game: siRNA in Bone Regeneration

Small Players Ruling the Hard Game: siRNA in Bone Regeneration

In Vitro Comparison of 2D-Cell Culture and 3D-Cell Sheets of Scleraxis-Programmed Bone Marrow Derived Mesenchymal Stem Cells to Primary Tendon Stem/Progenitor Cells for Tendon Repair

Functional analysis of bioactivated and antiinfective PDLLA – coated surfaces

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