Wisconsin National Primate Research Center
Over 60 years of life-saving research and humane animal care
Stem cells becoming neurons in James Thomson's lab at the Morgridge Insitute for Research

Stem cells form a neurosphere in James Thomson's lab at the Morgridge Institute for Research

Translational Stem Cell Technologies

The mission of the Translational Stem Cell Technologies Unit is to facilitate the translation of basic pluripotent stem cell research to human therapies by developing the basic resources broadly needed by investigators pioneering primate ES/iPSC cell-based transplantation models. Nonhuman primates provide a long-lived animal model that closely reflects human physiology and immunology that is essential for testing the safety and efficacy of iPS cell-based transplantation therapies. Under the direction of James Thomson, the unit developed nationally recognized expertise in the development of protocols for NHP ESC/iPSCs. This unit has been a central strength of the center, enabling many studies with primate ES and iPS cell lines and reagents.  These resources have not only been tools employed by WNPRC, but also around the country and the world. Furthermore, the unit partners with the Regenerative and Reproductive Medicine Working Group and Precision Medicine Unit at WNPRC to advance basic and translational science.

The WNPRC Translational Stem Cell Technologies Unit has three primary aims:

  • Improve the defined culture of primate ES/iPS cells and distribute cells and unique culture reagents to other investigators.
  • Provide primate ES/iPS cell culture, differentiation, and gene targeting training for other investigators.
  • Engineer ES/iPS cells to mitigate host immune response for future preclinical and clinical use.

GOALS AND SERVICES

  • Derivation and banking of transgene-free NHP induced pluripotent stem (iPS) cells, including MHC homozygous NHPs
  • Distributing NHP PSC’s and unique culture reagents
  • Develop protocols for efficient gene editing and providing NHP iPSC gene editing support for other investigators
  • Develop protocols for defined maintenance and growth of NHP iPSCs
  • Develop protocols to differentiate and purify NHP clinically relevant therapeutic cell types including cardiac, neural, blood, and endothelial cell types
  • Provide support for development of NHP PSC based transplantation and in vitro studies

CURRENT AND FUTURE TRANSLATIONAL PROJECTS SUPPORTED BY  STEM CELL RESOURCES

  • Pluripotent stem cell-based therapies for diseases of blood
  • Animal models for precision medicine
  • ESC derived vascular grafts for bypass therapy
  • Developing hypoimmunogenic ES/iPS cell lines for future preclinical and clinical use
  • Photoreceptor replacement therapy in nonhuman primates
  • Myocardial dysfunction
  • Immunogenicity of ES/iPS cell-derived tissues

KEY PERSONNEL AND CONTACT INFORMATION

NAME POSITION PHONE E-MAIL
JOHN MAUFORT, PH.D. Lead Scientist 608-890-4244 Email Dr. Maufort

Publications

Baik J, Ortiz-Cordero C, Magli A, Azzag K, Crist SB, Yamashita A, Kiley J, Selvaraj S, Mondragon-Gonzalez R, Perrin E, Maufort JP, Janecek JL, Lee RM, Stone LH, Rangarajan P, Ramachandran S, Graham ML, Perlingeiro RCR. Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem Cells. Cells. 2023 Apr 13;12(8):1147.

D’Souza SS, Kumar A, Maufort J, Weinfurter JT, Raymond M, Strelchenko N, Perrin E, Coonen J, Mejia A, Simmons H, Torbett BE, Reynolds M, Thomson JA, Slukvin I. Assessment of Safety and Immunogenicity of MHC homozygous iPSC-derived CD34+ Hematopoietic Progenitors in a NHP Model. Blood Adv. 2022 Apr 11:bloodadvances.2022006984.

D’Souza SS, Kumar A, Weinfurter J, Park MA, Maufort J, Tao L, Kang H, Dettle ST, Golos T, Thomson JA, Reynolds MR, Slukvin I. Generation of SIV-resistant T cells and macrophages from nonhuman primate induced pluripotent stem cells with edited CCR5 locus. Stem Cell Reports. 2022 Mar 17:S2213-6711(22)00136-9.

 

OLDER CITATIONS RESULTING FROM TRANSLATIONAL STEM CELL TECHNOLOGIES UNIT SUPPORT

  1. S. C. Vermilyea et al., In Vitro CRISPR/Cas9-Directed Gene Editing to Model LRRK2 G2019S Parkinson’s Disease in Common Marmosets. Sci Rep 10, 3447 (2020).
  2. A. Kumar et al., Generation of T cells from Human and Nonhuman Primate Pluripotent Stem Cells. Bio-Protocol 10, (2020).
  3. R. N. Aravalli, C. J. Steer, Utility of Common Marmoset (Callithrix jacchus) Embryonic Stem Cells in Liver Disease Modeling, Tissue Engineering and Drug Metabolism. Genes (Basel) 11, (2020).
  4. R. N. Aravalli, D. P. Collins, J. H. Hapke, A. T. Crane, C. J. Steer, Hepatic Differentiation of Marmoset Embryonic Stem Cells and Functional Characterization of ESC-Derived Hepatocyte-Like Cells. Hepat Med 12, 15-27 (2020).
  5. I. Rodriguez-Polo et al., Baboon induced pluripotent stem cell generation by piggyBac transposition of reprogramming factors. Primate Biol 6, 75-86 (2019).
  6. J. P. Maufort et al., Major Histocompatibility Complex-Matched Arteries Have Similar Patency to Autologous Arteries in a Mauritian Cynomolgus Macaque Major Histocompatibility Complex-Defined Transplant Model. J Am Heart Assoc 8, e012135 (2019).
  7. S. Wang et al., Interaction of p53 and ASPPs regulates rhesus monkey embryonic stem cells conversion to neural fate concomitant with apoptosis. Cell Cycle 17, 1146-1153 (2018).
  8. N. Eldabah et al., Altered Functional Expression of beta-Adrenergic Receptors in Rhesus Monkey Embryonic Stem Cell-Derived Cardiomyocytes. Stem Cells Dev 27, 336-346 (2018).
  9. S. C. Vermilyea et al., Real-Time Intraoperative MRI Intracerebral Delivery of Induced Pluripotent Stem Cell-Derived Neurons. Cell Transplant 26, 613-624 (2017).
  10. S. C. Vermilyea et al., Induced Pluripotent Stem Cell-Derived Dopaminergic Neurons from Adult Common Marmoset Fibroblasts. Stem Cells Dev 26, 1225-1235 (2017).
  11. T. Huma et al., Kisspeptin-10 treatment generated specific GnRH expression in cells differentiated from rhesus monkey derived Lyon NSCs. Neuroscience 349, 318-329 (2017).
  12. S. S. D’Souza et al., GSK3beta Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells. Stem Cell Reports 6, 243-256 (2016).
  13. L. Walker et al., Non-human primate and rodent embryonic stem cells are differentially sensitive to embryotoxic compounds. Toxicol Rep 2, 165-174 (2015).
  14. H. Chen et al., Characterization of glial-restricted precursors from rhesus monkey embryonic stem cells. Transl Neurosci 6, 244-251 (2015).
  15. T. Nii et al., Analysis of essential pathways for self-renewal in common marmoset embryonic stem cells. FEBS Open Bio 4, 213-219 (2014).
  16. T. Huma et al., Kisspeptin-10 modulates the proliferation and differentiation of the rhesus monkey derived stem cell line: R366.4. ScientificWorldJournal 2013, 135470 (2013).
  17. A. J. Harvey, S. Mao, C. Lalancette, S. A. Krawetz, C. A. Brenner, Transcriptional differences between rhesus embryonic stem cells generated from in vitro and in vivo derived embryos. PLoS One 7, e43239 (2012).
  18. Y. Chen et al., Folic acid deficiency inhibits neural rosette formation and neuronal differentiation from rhesus monkey embryonic stem cells. J Neurosci Res 90, 1382-1391 (2012).
  19. X. Wang et al., Hepatocytic differentiation of rhesus monkey embryonic stem cells promoted by collagen gels and growth factors. Cell Biol Int 35, 775-781 (2011).
  20. T. Maeda, R. Kurita, T. Yokoo, K. Tani, N. Makino, Telomerase inhibition promotes an initial step of cell differentiation of primate embryonic stem cell. Biochem Biophys Res Commun 407, 491-494 (2011).
  21. L. F. Jin, S. H. Ji, J. F. Yang, W. Z. Ji, Notch signaling dependent differentiation of cholangiocyte-like cells from rhesus monkey embryonic stem cells. Dongwuxue Yanjiu 32, 391-395 (2011).
  22. W. Zhao, H. Yuan, X. Xu, L. Ma, Isolation and initial application of a novel peptide that specifically recognizes the neural stem cells derived from rhesus monkey embryonic stem cells. J Biomol Screen 15, 687-694 (2010).
  23. Y. Tokuyama, S. L. Ingram, J. S. Woodward, C. L. Bethea, Functional characterization of rhesus embryonic stem cell-derived serotonin neurons. Exp Biol Med (Maywood) 235, 649-657 (2010).
  24. B. Maranca-Huwel, H. W. Denker, Epithelial-mesenchymal transition in rhesus monkey embryonic stem cell colonies: the role of culturing conditions. In Vitro Cell Dev Biol Anim 46, 516-528 (2010).
  25. S. Lu et al., Targeting of embryonic stem cells by peptide-conjugated quantum dots. PLoS One 5, e12075 (2010).
  26. C. B. Ware et al., Histone deacetylase inhibition elicits an evolutionarily conserved self-renewal program in embryonic stem cells. Cell Stem Cell 4, 359-369 (2009).
  27. X. Chen et al., Neural progenitors derived from monkey embryonic stem cells in a simple monoculture system. Reprod Biomed Online 19, 426-433 (2009).
  28. C. L. Bethea, A. P. Reddy, D. Pedersen, Y. Tokuyama, Expression profile of differentiating serotonin neurons derived from rhesus embryonic stem cells and comparison to adult serotonin neurons. Gene Expr Patterns 9, 94-108 (2009).
  29. H. Liu et al., Generation of induced pluripotent stem cells from adult rhesus monkey fibroblasts. Cell Stem Cell 3, 587-590 (2008).
  30. J. Leschik, S. Stefanovic, B. Brinon, M. Puceat, Cardiac commitment of primate embryonic stem cells. Nat Protoc 3, 1381-1387 (2008).
  31. C. B. Ware, S. W. Baran, A controlled-cooling protocol for cryopreservation of human and non-human primate embryonic stem cells. Methods Mol Biol 407, 43-49 (2007).
  32. C. A. Vandevoort, T. L. Thirkill, G. C. Douglas, Blastocyst-derived trophoblast stem cells from the rhesus monkey. Stem Cells Dev 16, 779-788 (2007).
  33. D. Rajesh et al., Differential requirements for hematopoietic commitment between human and rhesus embryonic stem cells. Stem Cells 25, 490-499 (2007).
  34. H. W. Denker, R. Behr, C. Heneweer, C. Viebahn, M. Thie, Epithelial-mesenchymal transition in Rhesus monkey embryonic stem cell colonies: a model for processes involved in gastrulation? Cells Tissues Organs 185, 48-50 (2007).
  35. S. W. Baran, C. B. Ware, Cryopreservation of rhesus macaque embryonic stem cells. Stem Cells Dev 16, 339-344 (2007).
  36. X. Zhang et al., Feeder layer- and serum-free culture of rhesus monkey embryonic stem cells. Reprod Biomed Online 13, 412-420 (2006).
  37. K. Schwanke et al., Generation and characterization of functional cardiomyocytes from rhesus monkey embryonic stem cells. Stem Cells 24, 1423-1432 (2006).
  38. M. Michelini et al., Primate embryonic stem cells create their own niche while differentiating in three-dimensional culture systems. Cell Prolif 39, 217-229 (2006).
  39. F. Li, S. J. Lu, G. R. Honig, Hematopoietic cells from primate embryonic stem cells. Methods Enzymol 418, 243-251 (2006).
  40. R. Kurita et al., Tal1/Scl gene transduction using a lentiviral vector stimulates highly efficient hematopoietic cell differentiation from common marmoset (Callithrix jacchus) embryonic stem cells. Stem Cells 24, 2014-2022 (2006).
  41. A. Fujimoto, S. M. Mitalipov, H. C. Kuo, D. P. Wolf, Aberrant genomic imprinting in rhesus monkey embryonic stem cells. Stem Cells 24, 595-603 (2006).
  42. J. A. Byrne, S. M. Mitalipov, D. P. Wolf, Current progress with primate embryonic stem cells. Curr Stem Cell Res Ther 1, 127-138 (2006).
  43. T. Li et al., Transplantable neural progenitor populations derived from rhesus monkey embryonic stem cells. Stem Cells 23, 1295-1303 (2005).
  44. T. Li et al., Homologous feeder cells support undifferentiated growth and pluripotency in monkey embryonic stem cells. Stem Cells 23, 1192-1199 (2005).
  45. R. Behr, C. Heneweer, C. Viebahn, H. W. Denker, M. Thie, Epithelial-mesenchymal transition in colonies of rhesus monkey embryonic stem cells: a model for processes involved in gastrulation. Stem Cells 23, 805-816 (2005).
  46. D. P. Wolf, H. C. Kuo, K. Y. Pau, L. Lester, Progress with nonhuman primate embryonic stem cells. Biol Reprod 71, 1766-1771 (2004).
  47. U. Salli et al., Serotonin neurons derived from rhesus monkey embryonic stem cells: similarities to CNS serotonin neurons. Exp Neurol 188, 351-364 (2004).
  48. D. S. Kaufman et al., Functional endothelial cells derived from rhesus monkey embryonic stem cells. Blood 103, 1325-1332 (2004).
  49. G. R. Honig, F. Li, S. J. Lu, L. Vida, Hematopoietic differentiation of rhesus monkey embryonic stem cells. Blood Cells Mol Dis 32, 5-10 (2004).
  50. Y. Pei, J. Ma, X. Zhang, W. Ji, Serum-free culture of rhesus monkey embryonic stem cells. Arch Androl 49, 331-342 (2003).
  51. L. Ma et al., Photodynamic inhibitory effects of three perylenequinones on human colorectal carcinoma cell line and primate embryonic stem cell line. World J Gastroenterol 9, 485-490 (2003).
  52. H. C. Kuo et al., Differentiation of monkey embryonic stem cells into neural lineages. Biol Reprod 68, 1727-1735 (2003).
  53. S. S. Chen et al., Multilineage differentiation of rhesus monkey embryonic stem cells in three-dimensional culture systems. Stem Cells 21, 281-295 (2003).
  54. J. D. Calhoun et al., Differentiation of rhesus embryonic stem cells to neural progenitors and neurons. Biochem Biophys Res Commun 306, 191-197 (2003).
  55. N. Nakatsuji, H. Suemori, Embryonic stem cell lines of nonhuman primates. ScientificWorldJournal 2, 1762-1773 (2002).
  56. S. J. Lu, C. Quan, F. Li, L. Vida, G. R. Honig, Hematopoietic progenitor cells derived from embryonic stem cells: analysis of gene expression. Stem Cells 20, 428-437 (2002).
  57. S. J. Lu, F. Li, L. Vida, G. R. Honig, Comparative gene expression in hematopoietic progenitor cells derived from embryonic stem cells. Exp Hematol 30, 58-66 (2002).
  58. V. S. Marshall, M. A. Waknitz, J. A. Thomson, Isolation and maintenance of primate embryonic stem cells. Methods Mol Biol 158, 11-18 (2001).
  59. F. Li, S. Lu, L. Vida, J. A. Thomson, G. R. Honig, Bone morphogenetic protein 4 induces efficient hematopoietic differentiation of rhesus monkey embryonic stem cells in vitro. Blood 98, 335-342 (2001).
  60. L. Jacobson, B. Kahan, A. Djamali, J. Thomson, J. S. Odorico, Differentiation of endoderm derivatives, pancreas and intestine, from rhesus embryonic stem cells. Transplant Proc 33, 674 (2001).
  61. J. A. Thomson, V. S. Marshall, J. Q. Trojanowski, Neural differentiation of rhesus embryonic stem cells. APMIS 106, 149-156; discussion 156-147 (1998).
  62. J. A. Thomson, V. S. Marshall, Primate embryonic stem cells. Curr Top Dev Biol 38, 133-165 (1998).
  63. J. A. Thomson et al., Pluripotent cell lines derived from common marmoset (Callithrix jacchus) blastocysts. Biol Reprod 55, 254-259 (1996).
  64. J. A. Thomson et al., Isolation of a primate embryonic stem cell line. Proc Natl Acad Sci U S A 92, 7844-7848 (1995).