Dataset Information

Renal Embolization-Induced Uremic Swine Model for Assessment of Next-Generation Implantable Hemodialyzers.

ABSTRACT: Reliable models of renal failure in large animals are critical to the successful translation of the next generation of renal replacement therapies (RRT) into humans. While models exist for the induction of renal failure, none are optimized for the implantation of devices to the retroperitoneal vasculature. We successfully piloted an embolization-to-implantation protocol enabling the first implant of a silicon nanopore membrane hemodialyzer (SNMHD) in a swine renal failure model. Renal arterial embolization is a non-invasive approach to near-total nephrectomy that preserves retroperitoneal anatomy for device implants. Silicon nanopore membranes (SNM) are efficient blood-compatible membranes that enable novel approaches to RRT. Yucatan minipigs underwent staged bilateral renal arterial embolization to induce renal failure, managed by intermittent hemodialysis. A small-scale arteriovenous SNMHD prototype was implanted into the retroperitoneum. Dialysate catheters were tunneled externally for connection to a dialysate recirculation pump. SNMHD clearance was determined by intermittent sampling of recirculating dialysate. Creatinine and urea clearance through the SNMHD were 76-105 mL/min/m² and 140-165 mL/min/m², respectively, without albumin leakage. Normalized creatinine and urea clearance measured in the SNMHD may translate to a fully implantable clinical-scale device. This pilot study establishes a path toward therapeutic testing of the clinical-scale SNMHD and other implantable RRT devices.

SUBMITTER: Moyer J

PROVIDER: S-EPMC10536310 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Renal Embolization-Induced Uremic Swine Model for Assessment of Next-Generation Implantable Hemodialyzers.

Moyer Jarrett J Wilson Mark W MW Sorrentino Thomas A TA Santandreu Ana A Chen Caressa C Hu Dean D Kerdok Amy A Porock Edward E Wright Nathan N Ly Jimmy J Blaha Charles C Frassetto Lynda A LA Fissell William H WH Vartanian Shant M SM Roy Shuvo S

Toxins 20230904 9

Reliable models of renal failure in large animals are critical to the successful translation of the next generation of renal replacement therapies (RRT) into humans. While models exist for the induction of renal failure, none are optimized for the implantation of devices to the retroperitoneal vasculature. We successfully piloted an embolization-to-implantation protocol enabling the first implant of a silicon nanopore membrane hemodialyzer (SNMHD) in a swine renal failure model. Renal arterial e ...[more]

PMID: 37755973

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Project description:Recently, oncology has moved to a new clinical practice, more personalized, called Predictive Oncology (PO). PO comes from our knowledge about tumor heterogeneity that implies that each disease, thus each patient, is unique. PO’s goal is to identify and administrate the right treatment to the right patient. For this, PO requires to go through 3 majors steps: 1. A good characterization of the tumor to identify candidates, 2. A well-established panel of drugs targeting the identified candidates, 3. A relevant model to functionally test these candidates. The first point could easily be addressed with recent technologies that now allow the Next Generation Sequencing (NGS) and/or the simultaneous analysis of transcriptomic profiles from thousands of patients. The last two points have not been efficiently achieved so far, which prevents PO to be really efficient. Indeed, even if NGS allows the identification of potential targets, the presence of a molecular candidate does not necessary means obligatory functional response. The number of drugs approved by the Food and Drug Administration remains limited and most frequent targets in solid tumors (for ex. RAS, P53, MYC, RB1 ...) still do not have specific drugs approved in clinic. Finally, available pre-clinical models still present many major inconvenient: * Chimiogrammes on 2D cultures are not sufficiently relevant to be really predictive of the in vivo situation; * Patient derived xenograft (PDX) are not adapted for clinical use because not all tumors graft and the time to develop a PDX is too long (several months), thus incompatible with the history of the disease (especially for most severe patients). Furthermore the host (NOD-SCID mouse) is immuno-depressed, preventing to objectively test antibodies-mediated drugs. Recently, the 3D cell culture technology has proven its superiority to predict drug response over classical 2D chimiogrammes. It consists in growing "mini-tissues", or organoid-derived from tumor/healthy tissues, thanks to the amplification of stem cells contained within the sample. The generated organoids are personalized and biologically relevant (organoids are expend form the patient’s stem cells which self-organized according to the architecture of the tissue they are originating from), they are genetically stable, their growth is compatible with patient’s disease history (organoids grow in few weeks), easy and convenient to achieve, even from small biological material quantities (0.5< x < 1cm3), and they can be amplified, frozen and thawed on demand. Moreover, organoids can be made more complex with the addition of other cell types (fibroblasts, immune cells ...). None of the actual available pre-clinical model regroups all these characteristics. The constitution of a "next generation" biobank of liver samples (Metastases to the liver and Hepato Cellular Adenocarcinoma) will be very useful in the context of predictive oncology. For this, a biopsy needs to be dissociated and grown in Matrigel, in presence of a well-defined list of growth factors. Once the culture is established, organoids can be frozen then defrost on demand. Our main objective is to evaluate the feasibility for building a biobank of liver-derived organoids, from liver metastases of colorectal cancers, hepatocellular adenoma and adenocarcinoma (waste tissues). Applications related to organoids derived from tumors are quasi indefinite, from drug screening assays, tests for novel therapies or original drug combinations, to patients’ stratifications or fundamental research. In our case, we are interested in building this a biobank in the prospect of using it to build the "next generation of model for predictive oncology" to study liver-related cancers and related drugs testing. Briefly, we want to implement these organoids with cells from the microenvironment in order to makes the global model more pertinent for drug testing. If successful, the generation of such biobank, including both tumor-derived organoids and healthy counterpart, could be really helpful for the scientific and medical community.

Dataset Information

Renal Embolization-Induced Uremic Swine Model for Assessment of Next-Generation Implantable Hemodialyzers.

Publications

Renal Embolization-Induced Uremic Swine Model for Assessment of Next-Generation Implantable Hemodialyzers.

Similar Datasets

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