Stem Cells and Regenerative Medicine
Regenerative medicine is the process of creating living, functional tissues to repair or replace tissue or organ function lost due to damage or congenital defects. Regenerative medicine has the potential to solve the problem of the shortage of organs available for donation. It also holds the promise of repairing or replacing damaged tissues and organs in the body by stimulating organs previously considered irreparable to heal themselves. The recent discovery of the reprogramming of adult cells to a pluripotent state provides opportunities to address a major problem of regenerative medicine: immune rejection of transplanted tissue. The ability to generate differentiated cells and tissues using cells from specific patients will facilitate individualized medicine and eventually lead to specialized therapies. The field is moving toward translation to clinical practice and is becoming increasingly dependent on animal models and information regarding the potential therapeutic efficacy of new technologies. Generating the correct type and quantity of the specific cell types required for replacement therapy is a significant challenge, as are the problems associated with introducing these cells into the proper environment in vivo and overcoming immune reactions. Finding solutions to these problems will require extensive testing in experimental animal models.
Along with rodents, several other animal species are being developed as models for various studies in the field of regenerative medicine. Understanding the properties and capabilities of stem cells derived from such animals as fish, rabbits, dogs, pigs, sheep, goats, and monkeys will increase the potential for the use of the most appropriate systems for modeling particular human disease conditions or for other medical applications. Non-rodent species, especially “large animal models,” provide important advantages for transplantation studies, including large size, similarity to human physiology and pathology, and longer life span, thus facilitating translation to studies in humans. The use of animal stem cells as a model for human cells in procedures related to regenerative medicine requires in-depth understanding of common regulatory pathways, as well as species-specific properties and their impact on potential therapeutic applications.
As part of the effort to respond to the needs and challenges identified by the research community and outlined in the report for the 2012 workshop “Improving Animal Models for Regenerative Medicine” organized by ORIP and representatives from several other NIH Institutes, ORIP published several funding opportunity announcements, including PAR-16-093, PAR-16-094, and PAR-16-322 "Improvement of Animal Models for Stem Cell-Based Regenerative Medicine"—(R01), (R21), and (R24), respectively. The intent of this initiative is to facilitate the use of stem cell–based therapies for regenerative medicine. The initiative focuses on the following areas: (1) comparative analysis of animal and human stem cells to provide information for selection of the most predictive and informative model systems, (2) development of new technologies for stem cell characterization and transplantation, and (3) improvement of animal disease models for stem cell–based therapeutic applications.
Apply for funding under PAR-21-167 "Development of Animal Models and Related Biological Materials for Research (R21)," RFA-OD-22-013 "Resource-Related Research Projects for Development of Animal Models and Related Materials (R24)," and Parent R01 PA-20-185, which currently support improvement of animal models for stem cell-based regenerative medicine.
Examples of projects funded by ORIP:
Transplantation of Testis Stem Cells in Large Animals
Ina Dobrinski
University of Calgary
Calgary, Canada
Novel Humanized Mouse Models For Engraftment of Tissue-Specific Human Macrophage Population
Michael Allen Brehm, Dale Leslie Greiner, Priti Kumar, Patricia Dorothy Schafer, Leonard Shultz
University of Massachusetts Chan Medical School
Worcester, MA
Translational Nonhuman Primate Regenerative Medicine and Gene Therapy/Genome Editing Resource Program
Alice F. Tarantal
University of California, Davis
Davis, CA
Developing second generation SCID pig models: filling the gaps to improve translation of therapeutics in regenerative medicine
Christopher Tuggle
Iowa State University
Ames, IA
Genetically Diverse Mouse Embryonic Stem Cells: A Platform for Cellular Systems Genetics
Christopher Lee Baker, Steven Carmen Munger, Laura G. Reinholdt
The Jackson Laboratory
Bar Harbor, ME
Developing preclinical xenograft models in zebrafish
David Michael Langenau
Massachusetts General Hospital
Boston, MA
Novel hematopoietic humanized mouse model to study CAR-T therapy-associated cytokine release syndrome
Yong Fan
Allegheny Health Network Research Institute
Pittsburgh, PA
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
Jorge A. Piedrahita
North Carolina State University
Raleigh, NC
Novel humanized mouse model of mucosal immunity
Anna Karolina Palucka
The Jackson Laboratory
Bar Harbor, ME
Developing a new chordate model for stem cell biology and regeneration
Anthony W. De Tomaso
University of California, Santa Barbara
Santa Barbara, CA
Mesenchymal stem/stromal cells to enhance cytotoxic T cell immunity during HIV infection
Amir Kol
University of California, Davis
Davis, CA
Direct generation of complex genetically-modified mouse models via embryonic stem cells
Duancheng Wen
Weill Cornell Medicine, Cornell University
New York, NY
Genetically enabling Hydra oligactis for comparative studies in development, regeneration and aging
Celina Juliano
University of California, Davis
Davis, CA
Establishment of xenopus stem cell lines
Nadege Gouignard
University of Wisconsin–Milwaukee
Milwaukee, WI
Establishing Acomys as a genetic platform for regeneration research
Kathleen Joyce Millen
Seattle Children's Hospital
Seattle, WA
