Derivation of Induced Pluripotent Stem Cells from the Baboon: A Nonhuman Primate Model for Preclinical Testing of Stem Cell Therapies

Abstract

Development of effective pluripotent stem cell-based therapies will require safety and efficacy testing in a clinically relevant preclinical model such as nonhuman primates (NHPs). Baboons and macaques are equally similar to humans genetically and both have been extensively used for biomedical research. Macaques are preferred for human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) research whereas baboons are preferred for transplantation studies because of the greater similarity of their anatomy and immunogenetic system to those of humans. We generated four induced pluripotent stem cell (iPSC) lines from skin cells of the olive baboon (Papio anubis). Each line shows the distinct morphology of primate pluripotent stem cells, including flat colonies with well-defined borders and a high nuclear/cytoplasm ratio. Each is positive for the pluripotency markers OCT4, SOX2, NANOG, and SSEA4. Pluripotency was confirmed in two lines by teratoma formation with representative tissues from each germ layer, whereas a third produced cells from all three germ layers following embryoid body differentiation. Three lines have a normal male karyotype and the fourth is missing the short arm of one copy of chromosome 18. This may serve as an in vitro model for the human developmental disorder 18p-, which impacts 1 in 50,000 births/year. These iPSC lines represent the first step toward establishing the baboon as a NHP model for developing stem cell-based therapies.

Studying human and nonhuman primate evolutionary biology with powerful in vitro and in vivo functional genomics tools

“…iPSCs have already been generated for both humans and a few nonhuman primate species, and similar resources could be created for any species from which fresh blood or skin tissue samples can be collected from at least one individual. Specifically, once a fresh sample is obtained and living, nucleated cells have been isolated, scientists can then reprogram these differentiated cells to induce pluripotency in a number of ways—with the most common and efficient method involving the activation of critical “pluripotency genes,” or Yamanaka factors, typically KLF4 , SOX2 , MYC , and POU5F1 (also known as Oct4 ) .…”

hiPSC-CM Monolayer Maturation State Determines Drug Responsiveness in High Throughput Pro-Arrhythmia Screen

“…Human based pre-clinical cardiotoxicity approaches are currently being developed and validated via collaboration between academic laboratories, federal regulatory agencies and the pharmaceutical industry 4 , 8 – 10 . The evolving human based approach for pre-clinical cardiotoxicity is called the Comprehensive in vitro Proarrhythmia Assay (CiPA for short).…”

Standards for Deriving Nonhuman Primate-Induced Pluripotent Stem Cells, Neural Stem Cells and Dopaminergic Lineage

“…Following the generation of human iPSC, [ 1 , 2 ] the derivation of the NHP-iPSCs has been reported from various NHP species, including the rhesus macaque, the marmoset, and the baboon [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. IPSCs from NHP play a unique role in cell biology and regenerative medicine as they offer the missing link between rodent and human studies aimed at understanding the basic mechanisms controlling pluripotency, cell fate determination, and pathogenesis of diseases.…”