Request for Information (RFI) Regarding Tissue Source Options for Generating Human Immune System (HIS) Mice

Notice Number: NOT-OD-19-093

Key Dates
Release Date: April 23, 2019
Response Date : May 29, 2019

Related Announcements

Issued by
National Institute of Allergy and Infectious Diseases (NIAID)
Division of Program Coordination, Planning and Strategic Initiatives, Office of Research Infrastructure Programs (ORIP)


The National Institutes of Health intends to invite applications to develop or further refine humanized mouse models that can be used to recapitulate aspects of human biology without reliance on the use of human fetal tissue (NOT-OD-19-042). Through this Request for Information (RFI), the National Institute of Allergy and Infectious Diseases (NIAID) and the Office of Research Infrastructure Programs (ORIP) seek input from the scientific community regarding alternatives to the use of fetal tissue for the generation of human immune system (HIS) mice. The information obtained from responses will aid the NIH in prioritizing tissue sources and types to be evaluated for developing alternatives.


Research using human fetal tissue and embryonic stem cell-derived systems has shed light on biomedical research questions ranging from understanding basic physiologic mechanisms of normal human tissue development, organ/tissue system functions, and disease processes to testing novel therapies for human diseases.

HIS mice are severely immune deficient mice that are reconstituted with human immune cells or tissues (derived from fetal or non-fetal sources), such that the immune system of the mouse is partially to primarily replaced with human immune cells and tissues. While no single HIS model is universally appropriate or optimal for all applications, various models can recapitulate key aspects of human T cell immunity but are less able to recapitulate human innate immunity and antibody responses, regardless of the human tissue source. Currently, eight humanized mouse strains constitute the major platforms used to generate HIS mice. These platforms use a variety of fetal and non-fetal derived human immune cells and tissues. New technologies raise the potential of reconstituting these model systems without fetal tissue and of yielding replicable and reproducible systems.

NIAID and ORIP plan to collect information on which tissues and sources are deemed important by the biomedical research community as potential alternatives to the use of fetal tissue to conduct detailed characterization, direct comparisons and further development of HIS mouse models.

Information Requested

This RFI invites the scientific community to provide comments regarding the tissues and quantities that will be needed for comparative studies. Examples include, but are not limited to, the following areas:

  • Post-birth sources of human cells/tissue (e.g., cord blood, neonatal, adult) for immune reconstitution;
  • Surgical versus post-mortem tissues;
  • Whole organs versus partial organs;
  • Banked versus fresh tissue;
  • Tissues from patients with specific disease conditions; and
  • Sample size.

Comments are also sought on the following:

  • Specific tissue collection and processing protocols;
  • Timelines from collection to use, frequency of need;
  • Minimal information needed about the donor and/or tissue;
  • Need for de-identification of specimens;
  • Storage and transportation requirements for the use of fresh vs frozen tissues;
  • Lead time needed for pre-notification of tissue shipment;
  • Potential legal issues to be considered;
  • Institutional issues and approvals (e.g. IRB, etc.);
  • Material transfer agreements; and
  • Other enhancement suggestions for provision of neonatal or adult tissues.


Responses will be accepted through May 29, 2019. Please submit responses via webform at Only submissions through the web will be considered for this RFI.

All interested extramural investigators and other interested parties are invited to respond. Responders are free to address any or all of the above items.

All individual responses will remain secure to the extent permitted by law. Any identifiers (e.g., names, institutions, email addresses, etc.) will be removed when responses are compiled. Only the processed, anonymized results will be shared internally with NIH staff members, as appropriate. The U.S. Government cannot guarantee the confidentiality of the information provided.

Responders are advised that the U.S. Government is under no obligation to acknowledge receipt of the information received or provide feedback to responders with respect to any information submitted. This RFI is for information and planning purposes only and should not be construed as a solicitation for applications or as an obligation on the part of the U.S. Government to provide support for any ideas identified in response to it. The U.S. Government will not pay for the preparation of any information submitted or for its use of that information. Responders should be aware that the information provided will be analyzed and may be used to develop future funding opportunity announcements and/or appear in various reports.


Responses to this RFI should only be submitted through the webform noted above in “Responses”.

Questions about this RFI may be directed to any of the NIH staff members listed below:

Mercy PrabhuDas, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3534

Oleg Mirochnitchenko, PhD
Office of Research Infrastructure Programs (ORIP)
Telephone: 301-435-0748