scholarly journals Feasibility of Gene Therapy for Tooth Regeneration by Stimulation of a Third Dentition

10.5772/52529 ◽  
2013 ◽  
Author(s):  
Katsu Takahashi ◽  
Honoka Kiso ◽  
Kazuyuki Saito ◽  
Yumiko Togo ◽  
Hiroko Tsukamoto ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Tooth Regeneration ◽  
Stimulation Of

scholarly journals Influence of Recombinant Codon-Optimized Plasmid DNA Encoding VEGF and FGF2 on Co-Induction of Angiogenesis

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 432 ◽  
Author(s):  
Ilnur I. Salafutdinov ◽  
Ilnaz M. Gazizov ◽  
Dilara K. Gatina ◽  
Ruslan I. Mullin ◽  
Alexey A. Bogov ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Stem Cell ◽  
Cell Therapy ◽  
Follicle Cells ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Skin Wounds ◽  
Angiogenic Growth Factors ◽  
Direct Gene ◽  
Stimulation Of

Several methods for the stimulation of skin wound repair have been proposed over the last few decades. The most promising among them are gene and stem cell therapy. Our present experiments combined several approaches via the application of human umbilical cord blood mononuclear cells (hUCB-MC) that were transfected with pBud-VEGF165-FGF2 plasmid (gene-cell therapy) and direct gene therapy using pBud-VEGF165-FGF2 plasmid to enhance healing of full thickness skin wounds in rats. The dual expression cassette plasmid pBud-VEGF165-FGF2 encodes both VEGF and FGF2 therapeutic genes, expressing pro-angiogenic growth factors. Our results showed that, with two weeks post-transplantation, some transplanted cells still retained expression of the stem cell and hematopoietic markers C-kit and CD34. Other transplanted cells were found among keratinocytes, hair follicle cells, endothelial cells, and in the derma. PCNA expression studies revealed that transplantation of transfected cells terminated proliferative processes in regenerating wounds earlier than transplantation of untransfected cells. In the direct gene therapy group, four days post-operatively, the processes of flap revascularization, while using Easy LDI Microcirculation Camera, was higher than in control wounded skin. We concluded that hUCB-MC can be used for the treatment of skin wounds and transfection these cells with VEGF and FGF2 genes enhances their regenerative abilities. We also concluded that the application of pBud-VEGF165-FGF2 plasmids is efficient for the direct gene therapy of skin wounds by stimulation of wound revascularization.

Stimulation of functional vessel growth by gene therapy

2010 ◽  
Vol 2 (2-3) ◽  
pp. 102-112 ◽  
Author(s):  
Petra Korpisalo ◽  
Seppo Ylä-Herttuala
Keyword(s):  
Gene Therapy ◽  
Vessel Growth ◽  
Stimulation Of

scholarly journals Stimulation of erythropoiesis by in vivo gene therapy: physiologic consequences of transfer of the human erythropoietin gene to experimental animals using an adenovirus vector

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 2946-2953 ◽  
Author(s):  
Y Setoguchi ◽  
C Danel ◽  
RG Crystal
Keyword(s):  
Gene Therapy ◽  
Blood Cell ◽  
Subcutaneous Administration ◽  
Adenovirus Vector ◽  
Fold Increase ◽  
Adenovirus Type ◽  
Stimulation Of Erythropoiesis ◽  
Adenovirus Type 5 ◽  
Stimulation Of

Abstract Erythropoietin (Epo), a 30.4-kD glycoprotein, is the principal regulator of erythropoiesis. To evaluate the concept that in vivo gene transfer might be used as an alternative to recombinant human Epo (rhEpo) in applications requiring a 1- to 3-week stimulation of erythropoiesis, the replication-deficient recombinant adenovirus AdMLP.Epo was constructed by deleting the majority of E1 from adenovirus type 5, and replacing E1 with an expression cassette containing the adenovirus type 5 major late promoter (MLP) and the human Epo gene, including the 32 cis-acting hypoxia response element. In vitro studies showed that infection of the human hepatocyte cell line Hep3B with AdMLP.Epo resulted in a 15-fold increase in Epo production in 24 hours that was enhanced to 116-fold in the presence of a hypoxic stimulus. One-time in vivo administration of AdMLP.Epo (7 x 10(9) plaque-forming units/kg) to the peritoneum of cotton rats caused a marked increase in red blood cell production, with a 2.6-fold increase in bone marrow erythroid precursors by day 4, and sevenfold increase in reticulocyte count by day 7. The hematocrit increased gradually, with a maximum of 64% +/- 4% at day 14 (compared with an untreated baseline of 46% +/- 2%), and a level of 55% +/- 1% at day 24. Furthermore, one-time subcutaneous administration of AdMLP.Epo caused an increase in hematocrit that peaked at 14 days (57% +/- 2%) and was still elevated at day 42. Hematocrit level in animals receiving subcutaneous administration of AdMLP.Epo sustained a long-term increase compared with animals receiving intraperitoneal administration. In the context of these observations, gene therapy with a single administration of an adenovirus vector containing the human EPO gene may provide a means of significantly augmenting the circulating red blood cell mass over the 1- to 3-week period necessary for many clinical applications.

scholarly journals Viral-mediated optogenetic stimulation of peripheral motor nerves in non-human primates

2018 ◽  
Author(s):  
Jordan J. Williams ◽  
Alan M. Watson ◽  
Alberto L. Vazquez ◽  
Andrew B. Schwartz
Keyword(s):  
Gene Therapy ◽  
Post Injection ◽  
Optical Stimulation ◽  
Stimulus Pulse ◽  
Opsin Expression ◽  
Optogenetic Stimulation ◽  
Cord Injury ◽  
Motor Nerves ◽  
Peripheral Motor ◽  
Stimulation Of

AbstractObjectiveReanimation of muscles paralyzed by disease states such as spinal cord injury remains a much sought after therapeutic goal of neuroprosthetic research. Optogenetic stimulation of peripheral motor nerves expressing light-sensitive opsins is a promising approach to muscle reanimation that may overcome several drawbacks of traditional methods such as functional electrical stimulation (FES). However, the utility of these methods has only been demonstrated in rodents to date, while translation to clinical practice will likely first require demonstration and refinement of these gene therapy techniques in non-human primates.ApproachThree rhesus macaques were injected intramuscularly with either one or both of two optogenetic constructs (AAV6-hSyn-ChR2-eYFP and/or AAV6-hSyn-Chronos-eYFP) to transduce opsin expression in the corresponding nerves. Neuromuscular junctions were targeted for virus delivery using an electrical stimulating injection technique. Functional opsin expression was periodically evaluated up to 13 weeks post-injection by optically stimulating targeted nerves with a 472 nm fiber-coupled laser while recording electromyographic (EMG) responses.Main ResultsOne monkey demonstrated functional expression of ChR2 at 8 weeks post-injection in each of two injected muscles, while the second monkey briefly exhibited contractions coupled to optical stimulation in a muscle injected with the Chronos construct at 10 weeks. A third monkey injected only in one muscle with the ChR2 construct showed strong optically coupled contractions at 5 ½ weeks which then disappeared by 9 weeks. EMG responses to optical stimulation of ChR2-transduced nerves demonstrated graded recruitment relative to both stimulus pulse-width and light intensity, and were able to track stimulus trains up to 16 Hz. In addition, the EMG response to prolonged stimulation showed delayed fatigue over several minutes.SignificanceThese results demonstrate the feasibility of viral transduction of peripheral motor nerves for functional optical stimulation of motor activity in non-human primates, a variable timeline of opsin expression in a primate model closer to humans, and fundamental EMG response characteristics to optical nerve stimulation. Subsequently, they represent an important step in translating these optogenetic techniques as a clinically viable gene therapy.

scholarly journals Stimulation of erythropoiesis by in vivo gene therapy: physiologic consequences of transfer of the human erythropoietin gene to experimental animals using an adenovirus vector

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 2946-2953 ◽  
Author(s):  
Y Setoguchi ◽  
C Danel ◽  
RG Crystal
Keyword(s):  
Gene Therapy ◽  
Blood Cell ◽  
Subcutaneous Administration ◽  
Adenovirus Vector ◽  
Fold Increase ◽  
Adenovirus Type ◽  
Stimulation Of Erythropoiesis ◽  
Adenovirus Type 5 ◽  
Stimulation Of

Erythropoietin (Epo), a 30.4-kD glycoprotein, is the principal regulator of erythropoiesis. To evaluate the concept that in vivo gene transfer might be used as an alternative to recombinant human Epo (rhEpo) in applications requiring a 1- to 3-week stimulation of erythropoiesis, the replication-deficient recombinant adenovirus AdMLP.Epo was constructed by deleting the majority of E1 from adenovirus type 5, and replacing E1 with an expression cassette containing the adenovirus type 5 major late promoter (MLP) and the human Epo gene, including the 32 cis-acting hypoxia response element. In vitro studies showed that infection of the human hepatocyte cell line Hep3B with AdMLP.Epo resulted in a 15-fold increase in Epo production in 24 hours that was enhanced to 116-fold in the presence of a hypoxic stimulus. One-time in vivo administration of AdMLP.Epo (7 x 10(9) plaque-forming units/kg) to the peritoneum of cotton rats caused a marked increase in red blood cell production, with a 2.6-fold increase in bone marrow erythroid precursors by day 4, and sevenfold increase in reticulocyte count by day 7. The hematocrit increased gradually, with a maximum of 64% +/- 4% at day 14 (compared with an untreated baseline of 46% +/- 2%), and a level of 55% +/- 1% at day 24. Furthermore, one-time subcutaneous administration of AdMLP.Epo caused an increase in hematocrit that peaked at 14 days (57% +/- 2%) and was still elevated at day 42. Hematocrit level in animals receiving subcutaneous administration of AdMLP.Epo sustained a long-term increase compared with animals receiving intraperitoneal administration. In the context of these observations, gene therapy with a single administration of an adenovirus vector containing the human EPO gene may provide a means of significantly augmenting the circulating red blood cell mass over the 1- to 3-week period necessary for many clinical applications.

Stimulation of Reparative Dentin Formation by Ex Vivo Gene Therapy Using Dental Pulp Stem Cells Electrotransfected with Growth/differentiation factor 11 (Gdf11)

2004 ◽  
Vol 15 (11) ◽  
pp. 1045-1053 ◽  
Author(s):  
Misako Nakashima ◽  
Koichiro Iohara ◽  
Masaki Ishikawa ◽  
Masataka Ito ◽  
Atsushi Tomokiyo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Dental Pulp ◽  
Ex Vivo ◽  
Dental Pulp Stem Cells ◽  
Reparative Dentin ◽  
Dentin Formation ◽  
I Gene ◽  
Reparative Dentin Formation ◽  
Stimulation Of

Effects of 5-5'-Diphenyl-2-thiohydantoin (DPTH) and Thyroxine on the Ultrastructure and Chemical Composition of Rat Liver

1971 ◽  
Vol 29 ◽  
pp. 570-571
Author(s):  
E. A. Elfont ◽  
R. B. Tobin ◽  
D. G. Colton ◽  
M. A. Mehlman
Keyword(s):  
Chemical Composition ◽  
Rat Liver ◽  
Future Study ◽  
Mode Of Action ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Effective Inhibitor ◽  
Biochemical Effects ◽  
Glycerophosphate Dehydrogenase ◽  
Stimulation Of

Summary5,-5'-diphenyl-2-thiohydantoin (DPTH) is an effective inhibitor of thyroxine (T4) stimulation of α-glycerophosphate dehydrogenase in rat liver mitochondria. Because this finding indicated a possible tool for future study of the mode of action of thyroxine, the ultrastructural and biochemical effects of DPTH and/or thyroxine on rat liver mere investigated.Rats were fed either standard or DPTH (0.06%) diet for 30 days before T4 (250 ug/kg/day) was injected. Injection of T4 occurred daily for 10 days prior to sacrifice. After removal of the liver and kidneys, part of the tissue was frozen at -50°C for later biocheailcal analyses, while the rest was prefixed in buffered 3.5X glutaraldehyde (390 mOs) and post-fixed in buffered 1Z OsO4 (376 mOs). Tissues were embedded in Araldlte 502 and the sections examined in a Zeiss EM 9S.Hepatocytes from hyperthyroid rats (Fig. 2) demonstrated enlarged and more numerous mitochondria than those of controls (Fig. 1). Glycogen was almost totally absent from the cytoplasm of the T4-treated rats.

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