APPLICATION — Custom Transplantation

Your Cells, Our Models:

the Perfect Combination

Custom model development with your hepatocyte of choice – any donor, any species

Custom Model Generation

Yecuris FRG® KO mice offer a powerful advantage over other humanized mouse models.  The platform can be transplanted with cells from any donor or species to yield an infinite number of phenotypic model variants.   We’ve worked with hundreds of clients for over a decade to incorporate normal, super, and mutant donors for drug metabolism, NASH, metabolic disease, and infectious disease.  Whether you’re looking to bridge data from previous experiments to a human-relevant model, or looking to create your own novel model, the FRG® KO platform is the ideal solution. 

HepaSpecies Cross-Species Donor Comparisons Using FRG Mice

Xenotransplanted FRG®KO mice offer the ideal platform for accelerated preclinical testing

Streamline your process. The efficiency of gene therapy vectors can vary widely from one species to the next, making pre-clinical validation difficult and costly. Yecuris offers FRG®KO mice repopulated with hepatocytes from a variety of species, including human, mouse, NHP, and others. These models can accelerate the development of your liver-targeted gene therapy vector in a cost-effective manner.

Advantages of xenografted FRG KO mice include:

  • Larger cohorts compared with NHP studies

  • Dramatically reduced viral doses required

  • Simplified regulatory requirements

  • Compare data from multiple species side-by-side

  • Consistency from a single platform

  • No pre-existing vector immunity

  • Perform studies in your own vivarium, or at Yecuris

Common species for the FRG cross-species comparison include:

  • Mouse or rat
  • Dog or pig
  • Non-human Primates: cynomolgus or rhesus
  • Human donors: male vs. female
  • Any combination of the above: mouse vs. cyno vs. human hepatocytes engrafted in the FRG mice

HepFinity™ Human Hepatocyte Expansion Services

Have you found that hepatocyte donors with genetic variants are becoming more and more difficult to procure? The FRG mice are often used as a bioreactor by taking a single vial of precious hepatocytes and allowing them to repopulate in vivo to generate 5X to 6X more hepatocytes. Here’s how it works.

 

  1. You send us your favorite lot (or vial) of cryopreserved hepatocytes
  2. We expand your rare or precious hepatocytes using the FRG KO mice
  3. The hepatocytes are isolated via perfusion, purified to remove any residual mouse hepatocytes, and prepared for delivery
  4. We ship the plateable fresh or cryopreserved human hepatocytes to your lab

Yecuris Custom Services

Custom Hepatocyte Transplantation
Yecuris offers custom hepatocyte transplantation with any donor that you require, from any species.  In addition, Yecuris has a selection of phenotypic donors including PNPLA3 and metabolic disease mutants for targeted human relevance.
Donor Performance Monitoring

Custom donors are monitored in-house by quantifying human albumin over time as well as survival rates.  These metrics are compared to Yecuris internal donors as a reference.

Drug Metabolism Studies
Animals are available as murinized or humanized FRG® KO mice, which can be repopulated with our in-house hepatocyte donors or as a custom with your donor of choice. Fully reconstituted animals are dosed with compounds according to study sponsor instructions, and samples are collected for in-process and downstream analysis.
Study Monitoring
Assessment of progression of disease states through the monitoring of body weight, food consumption, glucose, and insulin levels.
Gene Therapy Vector Administration
As the premier platform for In Vivo assessment of gene editing technologies, Yecuris study teams are highly skilled with multiple methods of Ex Vivo and In Vivo gene therapy administration.
Cell Isolation & Purification
Looking to use cells isolated from FRG® KO mice for your next In Vitro study?  Yecuris models act as bioreactors for hepatocytes with geometric expansion up to 100-fold.  We have developed processes for optimal isolation of the propagated hepatocytes with subsequent negative bead-based purification to remove residual mouse cells.  Our process yields cell products that are over 98% pure with the ability to be shipped in suspension, plated as fresh, or cryopreserved for future work.
Tissue Harvesting & Preparation
For studies that require terminal endpoints, Yecuris can harvest and prepare tissues as formalin fixed, OCT embedded, or flash frozen in liquid nitrogen.
Histological Assessment
Assessment of of samples by histology for structure and steatosis (H&E), hepatic ballooning (H&E), fibrosis (PSA), glycogen (PAS), humanization (FAH), and inflammation (CD45)
Cell & Tissue Sourcing
Looking for a hard to find donor profile?  Let our sourcing experts reach out to their network of tissue providers to locate the optimal donor for your application.
Custom Diet Formulation
Looking for a custom diet?  Let us help!  Our experts will help you formulate the ideal diet for use in FRG® KO mouse experiments.
Metabolic Caging
Used for excretion studies, Yecuris has metabolic caging options available for both cold and hot compound dosing.
Protocol Generation and Reporting
With over a decade of experience encompassing hundreds of studies across more than a dozen fields, you can depend on Yecuris scientists to work with you to develop well-formulated study strategies to assist you in achieving your critical experimental endpoints.
Expansion of Primary Hepatocytes
Primary hepatocytes do not expand in traditional cell culture systems.  The FRG® KO mouse has been used successfully to geometrically expand cell populations up to 100-fold through each generation of mouse.  The use of this model system as a hepatocyte bioreactor makes the procurement and expansion of rare cell types feasible for program scale development.
Talk to Our Scientists

Custom Transplantation Projects