Dataset Information

Allogenic multilayered fibroblast sheets promote anastomotic site healing in a rat model of esophageal reconstruction.

ABSTRACT:

Objective

Anastomotic leakage is a common and severe complication of esophageal reconstruction. Accordingly, there is a clinical need for novel methods to prevent it. We developed multilayered, growth factor-secreting fibroblast sheets that promote wound healing and angiogenesis. The present study aimed to assess the utility of allogenic multilayered fibroblast sheets in preventing esophageal anastomotic leakage in a rat model of esophageal reconstruction.

Methods

Allogenic multilayered fibroblast sheets prepared from oral mucosal tissues were implanted at esophageal anastomotic sites.

Results

The allogenic multilayered fibroblast sheet group had significantly higher burst pressure and collagen deposition compared to a control group five days postoperatively. The expression levels of collagen type I and III mRNAs around esophageal suture sites were higher in the allogenic multilayered fibroblast sheet group compared to the control group on postoperative days 0, 3, and 5. There was a trend toward lower anastomotic leakage and lower abscess scores in the allogenic multilayered fibroblast sheet group compared to the control group; however, these differences did not reach statistical significance. Allogenic multilayered fibroblast sheets completely disappeared at ten days after implantation. Further, no inflammation was observed at suture sites with implanted allogenic multilayered fibroblast sheets at five days after surgery.

Conclusion

Allogenic multilayered fibroblast sheets may represent a promising method of preventing esophageal anastomotic leakage.

SUBMITTER: Yamamoto N

PROVIDER: S-EPMC10250989 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Allogenic multilayered fibroblast sheets promote anastomotic site healing in a rat model of esophageal reconstruction.

Yamamoto Naohiro N Ueno Koji K Yanagihara Masashi M Kurazumi Hiroshi H Tanaka Yuya Y Oga Atsunori A Shimokawa Mototsugu M Harada Eijiro E Tanaka Toshiki T Hamano Kimikazu K

American journal of translational research 20230515 5

<h4>Objective</h4>Anastomotic leakage is a common and severe complication of esophageal reconstruction. Accordingly, there is a clinical need for novel methods to prevent it. We developed multilayered, growth factor-secreting fibroblast sheets that promote wound healing and angiogenesis. The present study aimed to assess the utility of allogenic multilayered fibroblast sheets in preventing esophageal anastomotic leakage in a rat model of esophageal reconstruction.<h4>Methods</h4>Allogenic multil ...[more]

PMID: 37303629

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Project description:The oral mucosa exhibits unique regenerative properties, sometimes referred to as foetal-like wound healing. Researchers from our institute have used sheets of oral mucosa epithelial cells (OMECs) for regenerative medicine applications including cornea replacement and oesophageal epithelial regeneration for stricture prevention. Here, we have isolated exosomes from clinical-grade production of OMEC sheets from healthy human donors (n = 8), aiming to evaluate the clinical potential of the exosomes to stimulate epithelial regeneration and to improve understanding of the mode-of-action of the cells. Exosomes were isolated from conditioned (cExo) and non-conditioned (ncExo) media. Characterization was performed using Western blot for common exosomal-markers: CD9 and flotillin were positive while annexin V, EpCam and contaminating marker GRP94 were negative. Nanoparticle tracking analysis revealed a diameter of ~120 nm and transmission electron microscopy showed a corresponding size and spherical appearance. Human skin fibroblasts exposed to exosomes showed dose-dependent reduction of proliferation and a considerable increase of growth factor gene expression (HGF, VEGFA, FGF2 and CTGF). The results were similar for both groups, but with a trend towards a larger effect from cExo. To study adhesion, fluorescently labelled exosomes were topically applied to pig oesophageal wound-beds ex vivo and subsequently washed. Positive signal could be detected after as little as 1 min of adhesion, but increased adhesion time produced a stronger signal. Next, labelled exosomes were added to full-thickness skin wounds in rats and signal was detected up to 5 days after application. cExo significantly reduced the wound size at days 6 and 17. In conclusion, exosomes from OMEC sheets showed pro-regenerative effects on skin wound healing. This is the first time that the healing capacity of the oral mucosa is studied from an exosome perspective. These findings might lead to a combinational therapy of cell sheets and exosomes for future patients with early oesophageal cancer.

Dataset Information

Allogenic multilayered fibroblast sheets promote anastomotic site healing in a rat model of esophageal reconstruction.

Objective

Methods

Results

Conclusion

Publications

Allogenic multilayered fibroblast sheets promote anastomotic site healing in a rat model of esophageal reconstruction.

Similar Datasets

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