In vivo reprogramming in inflammatory bowel disease

Wagnerová, Alexandra; Gardlík, Roman

doi:10.1038/gt.2013.43

Cited by 9 publications

(4 citation statements)

References 100 publications

(116 reference statements)

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“…The bacterial reprogramming phenomenon is one of the recently discovered aspects of human‐microbe interaction. Interestingly, bacteria can have a therapeutic application and can be used as a vector to transfer therapeutic gene sequences into the target cells of intestinal tissues, by providing them with a plasmid carrying reprogramming genes encoding pluripotency factors (Wagnerova & Gardlik ). The mechanisms and/or signaling that are involved in cell reprogramming by bacteria remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Reprogramming of human somatic cells by bacteria

Ito

Ohta

2015

Dev Growth Differ

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In general, it had been believed that the cell fate restriction of terminally differentiated somatic cells was irreversible. In 1952, somatic cell nuclear transfer (SCNT) was introduced to study early embryonic development in frogs. So far, various mammalian species have been successfully cloned using the SCNT technique, though its efficiency is very low. Embryonic stem (ES) cells were the first pluripotent cells to be isolated from an embryo and have a powerful potential to differentiate into more than 260 types of cells. The generation of induced pluripotent stem (iPS) cells was a breakthrough in stem cell research, and the use of these iPS cells has solved problems such as low efficiency and cell fate restriction. These cells have since been used for clinical application, disease investigation, and drug selection. As it is widely accepted that the endosymbiosis of Archaea into eukaryotic ancestors resulted in the generation of eukaryotic cells, we examined whether bacterial infection could alter host cell fate. We previously showed that when human dermal fibroblast (HDF) cells were incorporated with lactic acid bacteria (LAB), the LAB-incorporated HDF cells formed clusters and expressed a subset of common pluripotent markers. Moreover, LAB-incorporated cell clusters could differentiate into cells derived from each of the three germinal layers both in vivo and in vitro, indicating successful reprogramming of host HDF cells by LAB. In the current review, we introduce the existing examples of cellular reprogramming by bacteria and discuss their nuclear reprogramming mechanisms.

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Section: Discussionmentioning

confidence: 99%

Reprogramming of human somatic cells by bacteria

Ito

Ohta

2015

Dev Growth Differ

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“…Bactofection can be coupled with other current promising genetic technologies. In the past, we have hypothesized that bacteria can be used for the transfer of the Yamanaka factors into target cells to induce pluripotency potentially enabling regeneration of the diseased tissue (28), such the gut that is affected in the course of colitis (29). In an animal experiment we have shown that at least partially this might work.…”

Section: Bactofectionmentioning

confidence: 99%

Gene therapy using bacterial vectors

Celec

Gardlík

2017

Front Biosci

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Bacteria can be used for gene therapy via two strategies - either by transfection of eukaryotic host cells using bacteria (bactofection) or by alternative gene therapy that does not alter the host genome, but uses the prokaryotic expression system, which can be controlled or stopped from outside. While bactofection is optimal for gene substitution and DNA vaccination, alternative gene therapy is suitable for delivery of proteins and treatment with intracellular bactochondria. A specific form of bacteria-mediated gene therapy is transkingdom RNA interference. In this review, advantages and issues related to bacterial vectors as well as the major applications in biomedical research are summarized. Despite numerous published experiments, especially in the treatment of solid tumors and gut infections, progress in the clinics lags behind and major improvements in the safety, and even more in the efficiency, of these approaches are needed.

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“…However, despite the promising data on stem cell therapy of IBD, the use of induced pluripotent stem (iPS) cells for the treatment of IBD has not yet been assessed. In two recent reviews, we presented the rationale behind in vivo reprogramming using bacterial vectors for gene delivery into the colon tissue (15,16). We hypothesized that reprogramming intestinal cells into a pluripotent state could demonstrate potential for IBD therapy and prevention.…”

Section: Introductionmentioning

confidence: 99%

Effects of bacteria-mediated reprogramming and antibiotic pretreatment on the course of colitis in mice

Gardlík

Wagnerová

Celec

2014

Molecular Medicine Reports

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Since the original study by Takahashi and Yamanaka in 2006, there have been significant advances in the field of induced pluripotent stem cells. However, to the best of our knowledge, all of the studies published to date are based on ex vivo gene delivery and subsequent reimplantation of the cells. By contrast, in vivo reprogramming allows the direct administration of DNA encoding the reprogramming factors into the target tissue. In our previous study we demonstrated the beneficial effects of Salmonella‑mediated oral delivery of genes into colonic mucosa as a therapy for colitis. In the present study, the effect of the bacterial vector Salmonella typhimurium SL7207, carrying a plasmid encoding the reprogramming factors Sox2, Oct3/4 and Klf4, on colitis in mice was investigated. Therapeutic intervention, consisting of repeated gavaging following the induction of colitis, did not exhibit beneficial effects. However, preventive oral administration of the therapeutic bacterial strain resulted in improvements in weight loss, colon length and stool consistency. Recently it has been shown that antibiotic pretreatment may alleviate chemically induced colitis in mice. Therefore, in the present study it was investigated whether antibiotic pretreatment of mice was able to enhance colonization of the administered bacterial strain in the colon, and therefore improve therapeutic outcome. C57BL/6 mice were administered streptomycin and metronidazole for four days, prior to multiple oral administrations of therapeutic bacteria every other day. Following three gavages, mice were administered dextran sulfate sodium in their drinking water to induce colitis. Disease activity parameters, including stool consistency, weight loss and colon length, were improved in the group receiving antibiotics and bacterial vectors. These results indicate that antibiotic pretreatment may enhance bacterial gene delivery into the colon. Furthermore, the anticipated in vivo reprogramming of colon cells appears to have a beneficial effect on the severity of colitis. These effects, however, still require further analyses.

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In vivo reprogramming in inflammatory bowel disease

Cited by 9 publications

References 100 publications

Reprogramming of human somatic cells by bacteria

Reprogramming of human somatic cells by bacteria

Gene therapy using bacterial vectors

Effects of bacteria-mediated reprogramming and antibiotic pretreatment on the course of colitis in mice

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