Guideline Regarding Engraftment of Human Cells or Tissues Into
Immunodeficient Mice

# Introduction

Mice whose immune systems have been altered by genetic engineering,
spontaneous mutations or chemicals are widely used in biomedical
studies. The immunological deficiencies that make these animals useful
as models predispose them to a host of opportunistic and adventitious
agents that are not tolerated by immunologically competent mice. Also,
special attention must be given to possible zoonotic hazards posed by
transplantation of foreign tissues or cells into immunodeficient mice.
The Public Health Service (PHS) published guidelines for the prevention
and control of infectious diseases associated with xenotransplantation.
These guidelines can be found at:
http://www.fda.gov/cber/gdlns/xenophs0101.htm

The guidelines outlined below are intended for the introduction of human
cells or tissues into immunodeficient mice. **Prior to initiating any
studies involving animals and infectious agents approval is required
from the Animal Care and Use Committee and the Institutional Biosafety
Committee.**

# Recommended Procedure

Human samples should be prescreened for selected pathogens (e.g. HIV
1-2, EBV, HTLV 1-2, JCV, MOLUV, CMV, Hepatitis B and C) prior to use.
Presently at NCI-Frederick testing for the selected human pathogens is
available through the Laboratory of Molecular Technology; contact Kris
Pike (ext. 6897) to schedule testing. In addition, all cell lines and
tissues need to be MAP tested prior to use in animals; contact Peter
Gorelick (ext. 1134) to schedule testing. Material found to be free of
selected infectious agents could be used within the animal facility. In
cases where human tissue are known or shown to be infected, the level of
containment and procedures for the handling and disposal of materials
will be provided by the NCI-Frederick Biosafety Office. Investigators
working with such materials must have an approved *Pathogen
Registration\** on file. In cases where primary human tissue requires
immediate transfer into mice, the study will be conducted in a
quarantined area within a designated facility. The room should be posted
indicating that untested human tissues are being used. Persons working
with infectious agents or potentially infected material must be aware of
the potential hazards and must be trained and proficient in the
practices and techniques required for handling such material safely. The
facility manager in charge of the area in which the study is being
conducted in coordination with a member of the Biosafety Office is
responsible for providing the appropriate training and the S.O.P. All
mice will be maintained in microisolator cages or negatively ventilated
units (NOTE: PIV units must be operated as a negative pressure unit.
Operation of a PIV as a positive pressure unit is not only unacceptable,
but poses a probable risk of environmental contamination if the mice are
harboring an infectious agent) and the cages changed in a Biosafety
Level 2 (BSL2) changing station. Once the testing for adventitious
agents (human and murine) is received the level of containment will be
re-evaluated. The Biosafety Office will provide procedures for disposing
of potentially contaminated material.

*\*Registration of Research with Pathogens, Oncogenes, and Toxins* form
is available for download at:
http://web.ncifcrf.gov/campus/safety/usedocs.stm