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An in-depth analysis on vaginal wound healing post surgery: Transcriptomic effects of autologous micrografting versus acellular grafts

ABSTRACT: An in-depth analysis on vaginal wound healing post surgery: Transcriptomic effects of autologous micrografting versus acellular grafts

PROVIDER: PRJNA1057098 | ENA |

REPOSITORIES: ENA

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An in-depth analysis on vaginal wound healing post surgery: Transcriptomic effects of autologous micrografting versus acellular grafts

Project description:Understanding wound healing in vaginal tissue is crucial for improving female health outcomes, particularly in the context of surgeries like pelvic organ prolapse, post-radiation stricture formation and complications resulting from vaginal childbirth. Tissue-engineered grafts have proven successful for vaginal tissue repair, however, the mechanisms that stimulate tissue repair are unknown. This study aims to explore the transcriptomic signatures during tissue repair after using autologous micrografting versus acellular grafts in a rabbit model for surgical vaginal reconstruction. During a single surgical procedure, we created a graft for vaginal reconstruction consisting of autologous micrografts and supporting biomaterials. This graft was named "perioperative, layered, autologous, tissue expansion (PLATE)." We also produced acellular grafts that lacked autologous micrografts,. Our findings revealed distinct differences in gene expression patterns associated with wound healing, extracellular matrix organization, and smooth muscle regeneration between the two graft types. Notably, our findings revealed that micrografting showed an accelerated progression towards the final stages of wound healing, as evidenced by elevated matrix metalloproteinase (MMP) expression, particularly MMP-13. Additionally, Transforming Growth Factor Beta-1 (TGF-β1) emerged as an expected vaginal wound healing regulator. This study provides valuable insights into the molecular mechanisms of PLATE grafts and opens new avenues for the development of targeted therapies to improve wound healing in vaginal tissues.

2025-02-10 | GSE252016 | GEO

DNA methylation dynamics during esophageal epithelial regeneration following repair with acellular silk fibroin grafts in rat

Project description:Bi-layer silk fibroin (BLSF) scaffolds represent an emerging technology in the development of acellular biomaterials for esophageal repair. Their therapeutic potential is attributed to their robust mechanical properties, elasticity, and low immunogenicity. However, the underlying molecular mechanisms of scaffold-mediated wound healing processes in the esophagus remain unclear. Previous research has identified signaling cascades involved in neoepithelial regeneration in a rat model of onlay esophagoplasty with BLSF grafts, including c-MET, TrkA, and PI3K-Akt signaling. Interestingly, these pro-survival signaling cascades are largely governed by DNA methylation (DNAme). Such findings motivate us to apply reduced-representation bisulfite sequencing (RRBS) to characterize the temporal dynamics of DNAme in host and regenerated tissues up to 1 week post-operation. Globally, we observe hypermethylation at post-surgical repair timepoints and an inverse correlation between DNAme and the expression levels of differentially expressed proteins during regeneration. Site-specific hypomethylation targets genes associated with immune activation, which may be indicative of immune cell infiltration at the surgical implant site, while site-specific hypermethylation appears to target PI3K-Akt signaling. Our work provides mechanistic insight into the molecular processes governing esophageal regeneration, which can motivate therapeutic innovations toward temporal modulation of tissue regeneration during scaffold-mediated esophageal repair via epigenetic regulators that target key pathways.

2023-05-12 | GSE203028 | GEO

DNA methylation dynamics during esophageal epithelial regeneration following repair with acellular silk fibroin grafts in rat

Project description:DNA methylation dynamics during esophageal epithelial regeneration following repair with acellular silk fibroin grafts in rat

| PRJNA838203 | ENA

Proteomic profiles of synovial fluids derived from autologous chondrocyte implantation surgery

Project description:The pathology of failure in currently used biological treatments (cell therapies and microfracture) for cartilage repair or early osteoarthritis (OA) is poorly understood. We aimed to identify a reliable panel of biological predictors, present in synovial fluid, which can be used in the preoperative setting to optimise patient selection and therapy efficacy. The-long term aim is to reduce the number of patients who progress to end-stage OA and require knee replacement by making earlier, less invasive treatments more effective. In this first stage, we have taken synovial fluid aspirates from patients undergoing autologous chondrocyte implantation (ACI) at our centre in Oswestry, UK. Synovial fluids (SFs) were obtained from 14 ACI responders (mean Lysholm improvement of 33 (17-54)) and 13 non-responders (mean Lysholm decrease of 14 (4-46)) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Dynamic range compression of synovial fluids coupled with label-free quantification mass spectrometry (MS), was used in an unbiased approach to identify predictive markers of ACI success or failure and to investigate the biological pathways involved in the clinical response to ACI.

2017-07-04 | PXD005220 | Pride

Proteomic profiling of tissue-engineered, small-diameter vascular grafts implanted into the ovine carotid artery

Project description:Albeit vascular prostheses for the replacement of large arteries (e.g. aorta) are commercially available for decades, small-diameter vascular grafts (e.g., for coronary artery bypass graft surgery) still remain an unmet clinical need. Biostable polymers commonly used for the fabrication of aortic prostheses (e.g., poly(ethylene terephthalate) or expanded poly(tetrafluoroethylene)) have insufficient haemocompatibility to withstand thrombosis at low blood flow characteristic of small arteries (e.g., coronary artery). Hence, researchers endeavor to develop a biodegradable, tissue-engineered vascular graft (TEVG) to avoid the use of autologous blood vessels, such as saphenous vein or internal mammary artery, as conduits during the bypass surgery. Although a number of promising prototypes have been designed to date, none of them passed the pre-clinical trials successfully. Implantation into the ovine or porcine arteries is associated with thrombosis, neointimal hyperplasia, and aneurysms within one-year postoperation, precluding further clinical translation of TEVGs. Among the reasons of such impediment is that pathophysiology of TEVG implantation remains unclear and the molecular events occurring in the TEVG upon its implantation have not been properly investigated hitherto. Here, we for the first time performed a proteomic profiling of the TEVGs (n = 12) implanted into the ovine carotid arteries for one year and suffered from thrombosis to identify the signatures of TEVG failure in an unbiased manner. Contralateral intact ovine carotid arteries (n = 12) have been selected as a control group.

2022-11-26 | PXD036520 | Pride

Engineering transplantable jejunal mucosal grafts using primary patient-derived organoids for children with intestinal failure

Project description:Intestinal failure (IF), following extensive anatomical or functional loss of small intestine (SI), hasdebilitating long-term consequences on children1. Priority of care is to increase the child’s length of functional intestine, jejunum in particular, to promote nutritional independence2. Here we construct autologous jejunal mucosal grafts using primary patient biomaterials. We show that organoids derived from patients can be expanded efficiently in vitro. In parallel, we generate decellularized human intestinal matrix with intact nanotopography, which form optimal biological scaffolds. Remarkably, proteomic and Raman spectroscopy analyses reveal highly analogous biochemical profiles of human SI and colon scaffolds, indicating that both can be used interchangeably as platforms for intestinal engineering. Indeed, seeding jejunal organoids onto either scaffold type reliably reconstructs grafts that exhibit several aspects of physiological jejunal function with potential to survive after transplantation. Our findings provide proof-of-concept data for engineering IF patient-specific jejunal grafts, ultimately aiding in restoration of nutritional autonomy.

2020-09-16 | PXD019816 | Pride

Differences in Quantitative Crotonylated Protein Profiling of Human Arterial and Venous Grafts for Coronary Artery Bypass Surgery with Implications to Long-term Patency

Project description:The long-term survival of coronary artery bypass grafting (CABG) surgery depends on the patency of the grafts. A key problem is the lower patency of the saphenous vein (SV) compared to the arterial grafts such as internal thoracic artery (ITA) with unclear reasons despite of previous efforts to reveal them. We hypothesized that the intrinsic differences between the ITA and SV may involve the differences in post-translational modification (PTM) of proteins in these two types of vascular grafts. Hence, we applied PTM proteomics to uncover differences between ITA and SV, and to reveal a novel mechanism for the differences in long-term patency.

2021-06-01 | PXD026404 |

A scalable, GMP-compatible, autologous organotypic cell therapy for Dystrophic Epidermolysis Bullosa

Project description:Gene editing in induced pluripotent stem (iPS) cells has been hailed for enabling new cell therapies for various monogenetic diseases including dystrophic epidermolysis bullosa(DEB). However, manufacturing, efficacy, and safety roadblocks have limited the development of genetically corrected, autologous iPS cell-based therapies. We developed Dystrophic Epidermolysis Bullosa Cell Therapy (DEBCT), a new generation GMP-compatible (cGMP), reproducible, and scalable platform to produce autologous clinical-grade iPS cell-derived organotypic induced skin composite (iSC) grafts to treat incurable wounds of patients lacking type VII collagen (C7).

2024-06-30 | GSE229920 | GEO

Engineered exosomes reprogram Gli1+ cells in vivo to prevent calcification of vascular grafts and autologous pathological vessels

Project description:Engineered exosomes reprogram Gli1+ cells in vivo to prevent calcification of vascular grafts and autologous pathological vessels

| PRJNA943513 | ENA

Engineered exosomes reprogram Gli1+ cells in vivo to prevent calcification of vascular grafts and autologous pathological vessels

Project description:Engineered exosomes reprogrammed Gli1+ cells to promote SMC reconstruction and inhibit calcification in TEVBs and autologous pathological vessels.

2023-08-08 | GSE227179 | GEO

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