Advanced Services|Patient Derived Xenografts

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Patient-Derived Xenograft mice (PDX) are established by direct implantation of patient’s cancerous tissues (approximately 2-3 mm) into immunedeficient NSG mice. The tumors that are successfully engrafted can be further expanded by transferring small tumor pieces to more mice and creating a mice avatar for the tumor sample. The engraftment success rate varies between tumor types (for example, high for breast and melanoma and low for lung). Time for tumor growth depends on different factors, mainly tumor aggressiveness and could be 1-6 months for initial tumor engraftment.

Roni Oren

Location: The Centre for Comparative Medicine

The use of PDX models allows for the expansion of the tumor tissue, to provide the researcher a preform for different experimental procedures in vivo and to remove tumor mass for ex vivo experiments, including genomic analysis, histology, metabolic analysis etc. The use of PDX as a model to study cancer is rapidly expanding and replaces/supports work using human cell line xenografts.
The PDX service unit is a part of the Moross Integrated Cancer Center (MICC).  In the unit we support all aspects of establishment and utilization of PDX cancer models.

Obtaining PDX models

The tumor samples are obtained in collaboration with different hospitals in Israel.
PDX mice models are also available commercially through The Jackson Laboratory.

Sample processing

Upon receiving a new tumor sample it is processed as soon as possible according to specific needs. In general, a piece of the sample is implanted to NSG mice, another section is sent for health testing (see below), a section is also sent to histology for pathological evaluation and the remaining tumor is kept in the tumor bank (Human Tissue Samples Bank) for future usage.

PDX management tool

For tracking and managing the PDX bearing mice, all experimental procedures and frozen samples is done using a Weizmann developed web tool
All mice are tagged with a unique identifier chip (implanted subcutaneous). Tubes, Histology cassettes and slides are labeled with a unique barcode and tracked.

Introduction of PDXs

Introduction of PDXs to Weizmann animal facilities has to be approved for both ethics and health issues:

  • Studies involving human subjects or human originated specimens require approval of the WIS bioethics committee
  • Samples obtained from patients must be obtained under a Helsinki approval submitted by the physician
  • IACUC approved protocol is required for the use of lab animals in the study
  • All samples originated from patients must be submitted to diagnostic health hazards evaluation

Health hazards evaluation - Instructions to users

Animal procedures involving PDXs (with IACUC approval) could be carried in the dedicated room (in MAMTAK). In parallel, a sample from each specimen should tested at an outside source (IDEXX-RADIL).
From previous experience, the time period between sample shipment and receiving the result is about 10 days. Further handling of the mice/tumor approved only after negative results.
If the cells are first grown in the lab and inoculate into the mice only after the (negative) health status is confirmed, then the animal study can be done without further confirmation.

Sample submission for health testing

Each specimen should be stored in a cryovial containing 1-10*10^6 cells or 0.5 ml, or a piece of tissue; on dry ice.
Call Dr. Roni Oren to arrange a test.
Alongside the sample, provide the following information:

  • Name of PI
  • Specimen list (matching the labels on the vials)
  • Date (when you intend to bring in the specimens)

We prefer to ship the specimens to IDEXX-RADIL on Mondays or Tuesdays before noon. If necessary, we will keep the specimens in -80C until shipping.
Human specimens will be tested for the h-IMPACT profile.