“High Profile Diseases” are written by individual NPRC Core Scientists who are experts in the specific subject of each article. Before publication on the website, each article is reviewed by representatives of all seven NPRCs.
Jordana Lenon (WNPRC)
The National Primate Research Centers have been responsible for groundbreaking advances in pluripotent stem cell research since 1995. (See timeline.) Scientists use pluripotent stem cells as a basic research tool to understand the human body, for pharmaceutical development and drug toxicity testing, to screen for environmental compounds that may be harmful to humans, and for preclinical tissue and organ transplant studies. Embryonic stem cells come from leftover lab-fertilized embryos donated by patients at in vitro fertilization clinics. Induced pluripotent stem cells (iPS cells) are genetically reprogrammed skin, fat or other mature cells that act like embryonic stem cells but can be derived from an individual’s own cells to study and potentially treat a particular genetic or degenerative disease in that individual.
As pluripotent stem cell research moves from bench to bedside, large animals such as nonhuman primates, pigs and sheep are becoming more important for preclinical studies. For example, researchers are using heart, bone, and retinal cells grown from both ES and iPS cells to regenerate healthy cardiac tissue after myocardial infarction, lost bone and cartilage due to joint injury or degeneration, and retinal cells to restore vision in patients with juvenile and age-related macular degeneration.
Pluripotent stem cells can also be used to grow mesenchymal stem cells, which are normally found in bone marrow but are difficult to extract in large quantities for basic and preclinical research. Clinicians hope to grow large numbers of mesenchymal stem cells from a patient’s own iPS cells, to regenerate bone marrow for cancer treatment: There are not enough matched bone marrow donors and even autologous (self) bone marrow extraction, cryopreservation and transplant after cancer treatment is a risky process and not always successful. Mesenchymal stem cells and related types of stem cells are showing potential for therapeutic, protective and regenerative benefits in other tissues and organs as well.
NPRC scientists are also using iPS cells to grow dopaminergic neurons for researching Parkinson’s disease therapies, pancreatic beta cells for diabetes studies, and motor neurons to study ALS. One NPRC scientist is interested in using iPS cells as a source of cells to produce oocytes for fertility treatment in cancer survivors who suffer from ovarian insufficiency. Nonhuman primate models will be the critical stepping stone between many of these basic stem cell research studies and human treatments.
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Vodyanik MA, Bork JA, Thomson JA, Slukvin II. Human embryonic stem cell-derived CD34+ cells: efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential. Blood. 2005 Jan 15;105(2):617-26. PMID:15374881. PMCID unavailable.
Ludwig TE, Levenstein ME, Jones JM, Berggren WT, Mitchen ER, Frane JL, Crandall LJ, Daigh CA, Conard KR, Piekarczyk MS, Llanas RA, Thomson JA. Derivation of human embryonic stem cells in defined conditions. Nat Biotechnol. 2006 Feb;24(2):185-7. PMID:16388305. PMC unavailable.
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Tarantal AF, Lee CC, Batchelder CA, Christensen JE, Prater D, Cherry SR. Radiolabeling and in vivo imaging of transplanted renal lineages differentiated from human embryonic stem cells in fetal rhesus monkeys. Mol Imaging Biol. 2012 Apr;14(2):197-204. PMID: 21479709. PMC4224287.
Shi Q, Hodara V, Simerly CR, Schatten GP, VandeBerg JL. Ex vivo reconstitution of arterial endothelium by embryonic stem cell-derived endothelial progenitorcells in baboons. Stem Cells Dev. 2013 Feb 15;22(4):631-42. PMID: 22931470. PMC3564485.
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Tachibana M, Amato P, Sparman M, Gutierrez NM, Tippner-Hedges R, Ma H, Kang E, Fulati A, Lee HS, Sritanaudomchai H, Masterson K, Larson J, Eaton D, Sadler-Fredd K, Battaglia D, Lee D, Wu D, Jensen J, Patton P, Gokhale S, Stouffer RL, Wolf D, Mitalipov S. Human embryonic stem cells derived by somatic cell nuclear transfer. Cell. 2013 Jun 6;153(6):1228-38. PMID: 23683578. PMC3772789.
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Salih SM, Ringelstetter AK, Elsarrag MZ, Abbott DH, Roti EC. Dexrazoxane abrogates acute doxorubicin toxicity in marmoset ovary. Biol Reprod. 2015 Mar;92(3):73. PMID: 25609833. PMC4367967.
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There are currently 138 publications available for Induced pluripotent Stem Cells in Regenerative Medicine.
Chen J, Nefzger CM, Rossello FJ, Sun YBY, Lim SM, Liu X, de Boer S, Knaupp AS, Li J, Davidson KC, Polo JM, Barberi T
Fine Tuning of Canonical Wnt Stimulation Enhances Differentiation of Pluripotent Stem Cells Independent of β-Catenin-Mediated T-Cell Factor Signaling.
Stem Cells 2018 Feb; (): .
D'Souza SS, Kumar A, Slukvin II
Functional Heterogeneity of Endothelial Cells Derived from Human Pluripotent Stem Cells.
Stem cells and development 2018 Apr; 27(8): 524-533.
Ke M, He Q, Hong D, Li O, Zhu M, Ou WB, He Y, Wu Y
Leukemia inhibitory factor regulates marmoset induced pluripotent stem cell proliferation via a PI3K/Akt‑dependent Tbx‑3 activation pathway.
Int. J. Mol. Med. 2018 Jul; 42(1): 131-140.
Liu YW, Chen B, Yang X, Fugate JA, Kalucki FA, Futakuchi-Tsuchida A, Couture L, Vogel KW, Astley CA, Baldessari A, Ogle J, Don CW, Steinberg ZL, Seslar SP, Tuck SA, Tsuchida H, Naumova AV, Dupras SK, Lyu MS, Lee J, Hailey DW, Reinecke H, Pabon L, Fryer BH, MacLellan WR, Thies RS, Murry CE
Human embryonic stem cell-derived cardiomyocytes restore function in infarcted hearts of non-human primates.
Nat. Biotechnol. 2018 Aug; 36(7): 597-605.
Navara CS, Chaudhari S, McCarrey JR
Optimization of culture conditions for the derivation and propagation of baboon (Papio anubis) induced pluripotent stem cells.
PLoS ONE 2018 ; 13(3): e0193195.
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A starring role for nonhuman primates in the stem cell story
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How human embryonic stem cells sparked a revolution
November 18, 2017
A decade after stem cell feat, research ramps up
December 2, 2016
Pluripotent stem cells: the last 10 years
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Scientists developing MRI-guided stem cell delivery method
September 29, 2016
Thomson honored for stem cell research legacy
September 5, 2014
Disease in a dish approach could aid Huntington's disease discovery
April 30, 2014
Scientists regenerate heart muscle in primates