Gene-Activated Matrix Comprised of Atelocollagen and Plasmid DNA Encoding BMP4 or Runx2 Promotes Rat Cranial Bone Augmentation

Umebayashi, Mayumi; Sumita, Yoshinori; Kawai, Yousuke; Watanabe, Sumiko; Asahina, Izumi

doi:10.1089/biores.2014.0057

Cited by 20 publications

(14 citation statements)

References 46 publications

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“…When GAM is inserted into a bone defect, host MSCs entering the scaffold are transfected by plasmid and consequently secrete the osteogenic gene product. The usefulness of GAM in bone tissue regeneration was investigated by Umebayashi et al [2015]. GAM with atelocollagen containing cDNA of BMP4 (pBMP4) or Runx2 (pRunx2) was transplanted into the cranial bone surface under the periosteum of F344 rats.…”

Section: Future Directions Of Msc Therapy In Clinical Practicementioning

confidence: 99%

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

Oryan

Kamali²,

Moshiri³

et al. 2017

Cells Tissues Organs

285

204

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Healing and regeneration of bone injuries, particularly those that are associated with large bone defects, are a complicated process. There is growing interest in the application of osteoinductive and osteogenic growth factors and mesenchymal stem cells (MSCs) in order to significantly improve bone repair and regeneration. MSCs are multipotent stromal stem cells that can be harvested from many different sources and differentiated into a variety of cell types, such as preosteogenic chondroblasts and osteoblasts. The effectiveness of MSC therapy is dependent on several factors, including the differentiating state of the MSCs at the time of application, the method of their delivery, the concentration of MSCs per injection, the vehicle used, and the nature and extent of injury, for example. Tissue engineering and regenerative medicine, together with genetic engineering and gene therapy, are advanced options that may have the potential to improve the outcome of cell therapy. Although several in vitro and in vivo investigations have suggested the potential roles of MSCs in bone repair and regeneration, the mechanism of MSC therapy in bone repair has not been fully elucidated, the efficacy of MSC therapy has not been strongly proven in clinical trials, and several controversies exist, making it difficult to draw conclusions from the results. In this review, we update the recent advances in the mechanisms of MSC action and the delivery approaches in bone regenerative medicine. We will also review the most recent clinical trials to find out how MSCs may be beneficial for treating bone defects.

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Section: Future Directions Of Msc Therapy In Clinical Practicementioning

confidence: 99%

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

Oryan

Kamali²,

Moshiri³

et al. 2017

Cells Tissues Organs

285

204

View full text Add to dashboard Cite

show abstract

“…Administration of pDNA is considered safe, especially when employed at a low dose [32]. Clinical study of pDNA has been conducted at 4-16 mg by intra-muscular injection [33,34].…”

Section: Discussionmentioning

confidence: 99%

Effects of Tissue Pressure on Transgene Expression Characteristics via Renal Local Administration Routes from Ureter or Renal Artery in the Rat Kidney

et al. 2020

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We previously developed a renal pressure-mediated transfection method (renal pressure method) as a kidney-specific in vivo gene delivery system. However, additional information on selecting other injection routes and applicable animals remains unclear. In this study, we selected renal arterial and ureteral injections as local administration routes and evaluated the characteristics of gene delivery such as efficacy, safety, and distribution in pressured kidney of rat. Immediately after the naked pDNA injection, via renal artery or ureter, the left kidney of the rat was pressured using a pressure controlling device. Transfection efficiency of the pressured kidney was about 100-fold higher than that of the injection only group in both administration routes. The optimal pressure intensity in the rat kidney was 1.2 N/cm2 for renal arterial injection and 0.9 N/cm2 for ureteral injection. We found that transgene expression site differs according to administration route: cortical fibroblasts and renal tubule in renal arterial injection and cortical and medullary tubule and medullary collecting duct in ureteral injection. This is the first report to demonstrate that the renal pressure method can also be effective, after renal arterial and ureteral injections, in rat kidney.

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“…This “cell free” gene-activated scaffold platforms have the advantage of locally transfecting the host cells that infiltrate and proliferate on the scaffold implanted at the defect site, without the need of ex vivo or in vitro transfection [55]. Umebayashi et al have successfully used this method in the transplantation of GAMs for the expression of BMP-4 and Runx2 in the cranial bone surface under the periosteum of F344 rats, resulting in a GAM dose-dependent bone induction [56]. Another study has shown an accelerating bone repair in rat critical-size calvarial defect when nanoparticles containing both BMP-2 and VEGF plasmids were incorporated into bone mimicking collagen hydroxyapatite scaffolds [57].…”

Section: Molecular Candidates and Common Methods To Genetically-enmentioning

confidence: 99%

Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects

Freitas

Santos

Gonçalves

et al. 2019

IJMS

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The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem/stromal cells (MSCs) are able to promote bone regeneration. Their beneficial effects can be improved by modulating the expression levels of specific genes with the purpose of stimulating MSC proliferation, osteogenic differentiation or their immunomodulatory capacity. In this context, the genetic engineering of MSCs is expected to further enhance their pro-regenerative properties and accelerate bone healing. Herein, we review the most promising molecular candidates (protein-coding and non-coding transcripts) and discuss the different methodologies to engineer and deliver MSCs, mainly focusing on in vivo animal studies. Considering the potential of the MSC secretome for bone repair, this topic has also been addressed. Furthermore, the promising results of clinical studies using MSC for bone regeneration are discussed. Finally, we debate the advantages and limitations of using MSCs, or genetically-engineered MSCs, and their potential as promoters of bone fracture regeneration/repair.

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Gene-Activated Matrix Comprised of Atelocollagen and Plasmid DNA Encoding BMP4 or Runx2 Promotes Rat Cranial Bone Augmentation

Cited by 20 publications

References 46 publications

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

Effects of Tissue Pressure on Transgene Expression Characteristics via Renal Local Administration Routes from Ureter or Renal Artery in the Rat Kidney

Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects

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