WNPRC stem cell pioneer James Thomson achieved the first successful derivations of nonhuman primate (NHP) and human embryonic stem cells. Dr. Thomson has since developed technologies for generations of transgene-free human and NHP induced pluripotent stem (iPS) cells in defined conditions for production of clinical grade iPS cells. He has also developed defined culture conditions for growth and maintenance of pluripotent stem cells as well as protocols for efficient gene editing in pluripotent stem cells as well as made advancements into iPS cell-derived cell products.
Because iPS cells can be derived from the patient, they offer the possibility to generate autologous therapeutic cells in unlimited numbers and avoid HLA alloimmunization. However, the high costs of personalized stem cell therapy and its complexity make it currently impractical for broad application. Creation of iPS cell banks has been proposed as an approach to supply HLA-matched PS cell derivatives. The banking of iPS cells from HLA-homozygous donors has been suggested to be an effective way to provide a scalable off-the-shelf supply of immunologically compatible cells for cellular therapies and maximize the utility of stem cell banking.
Dr. Thomson started a project to establish a NHP model for banking major histocompatibility (MHC) homozygous iPS cell lines for cellular therapies employing Mauritian cynomolgus macaques. These animals have a very limited MHC diversity and provide a unique opportunity to rapidly select MHC homozygous and MHC and blood group-identical animals, or animals with well-defined MHC mismatches, by genetic screening. Dr. Thomson has also began developing an arterial transplant model in Mauritian cynomolgus macaques. Performing arterial transplants between matched and mismatched Mauritian cynomolgus macaques will evaluate the immunological value of banking MHC homozygous iPS cells and eventually test the function of iPS cell-derived engineered blood vessels.
By developing basic resources broadly needed by all regenerative medicine investigators, Dr. Thomson’s laboratory played a central part in establishing pluripotent stem cell based therapies. To facilitate the translation of basic pluripotent stem cell research to human therapies, the Stem Cell Resources Unit develops expertise and reagents broadly needed by investigators developing primate iPS cell-based transplantation models, with a new focus on a unique population of MHC homozygous cynomolgus macaques.
GOALS AND SERVICES
- Derivation and banking of iPS cells from MHC homozygous NHPs
- Develop protocols for efficient gene editing and providing NHP iPS cell gene editing services for other investigators
- Develop protocols for defined maintenance and growth of NHP iPS cells
- Develop protocols to differentiate and purify specific NHP PSC derivatives
- Proved large-scale production of NHP pluripotent stem cells and their derivatives for transplantation and in vitro studies
- Coordinate and assist in animal procedures for PS cell transplantation studies
- Developing a MHC-defined NHP vascular transplant model to assess efficacy of HLA homozygous iPS cell banks and preclinical evaluation of iPS cell-based therapies for vascular disease
- Stem cells for modeling early development: Ted Golos, Ph.D. (Dept. of Comparative Biosciences, WNPRC). The Stem Cell Resources Unit has provided Dr. Golos’ group with cell culture training, reprogramming training, reprogramming vectors, cell culture reagents, and lab space for their marmoset reprogramming efforts.
- Pluripotent stem cell-based therapies for diseases of blood: Igor Slukvin, M.D., Ph.D (Dept. of Pathology, WNPRC). The Stem Cell Resources Unit has provided Dr. Slukvin’s group with iPS cells from rhesus and cynomolgus macaques. We have also provided cell sorting, next generation sequencing support, and media reagents.
- Myocardial dysfunction: Timothy Kamp, M.D., Ph.D., FACS (Dept. of Medicine), Manfred Boehm, Ph.D. (NHLBI). The Stem Cell Resources Unit has provided several rhesus pluripotent stem cell lines, technical support for culture conditions, and quality controlled media reagents to enable NHP cardiovascular studies.
- Stem cell approaches to transplant tolerance: Dixon Kaufman, M.D., Ph.D., FACS (Dept. of Surgery). Stem Cell Resources Unit has provided MHC-defined rhesus macaque iPS cells for Dr. Kaufman’s group’s kidney transplantation project to examine the mechanisms of immune tolerance in collaboration with Dr. Slukvin.
- Parkinson’s disease: Marina Emborg, M.D., Ph.D. (WNPRC). The Stem Cell Resources Unit has provided lab space, stem cell-specific cell culture training, media reagents, and assistance with lineage specific differentiation for Dr. Emborg’s marmoset embryonic stem cell Parkinson’s disease modeling studies.
- Immunogenicity of ES/iPS cell-derived tissues: William Burlingham, Ph.D. (Dept. of Surgery). Collaboration with Dr. Slukvin to adapt tolerance approaches to autologous iPS cell transplantation.
- Pluripotent stem cell derivation and vascular biology: James Thomson, V.M.D., Ph.D. (Morgridge Institute for Research, WNPRC). The Stem Cell Resources Unit continues to leverage technologies developed within the Thomson lab and apply them to NHP-based models, including cellular-based therapies for vascular disease and banking NHP MHC homozygous iPS cells.
|JAMES THOMSON, V.M.D., PH.D.||Director of Regenerative Biology at the Morgridge Institute for Research||608-316-4348||Email Dr. Thomson|
|JOHN MAUFORT, PH.D.||Assistant Scientist||608-890-4244||Email Dr. Maufort|
|ELIZABETH PERRIN, B.S.||Associate Research Specialist||608-890-4244||Email Ms. Perrin|