Prostaglandin E₂ (PGE₂) is the most biologically active and well-studied prostaglandin. It binds with very high affinity to the EP1, EP2, EP3, and EP4 receptors (Ki = 9.1, 4.9, 0.33, 0.79 nM respectively). (Abramovitz et al., Bos et al.)
MAINTENANCE AND SELF-RENEWAL
· Required for the development of hematopoietic stem cells (HSCs) in mice and zebrafish (North et al.).
· Improves engraftment of mouse HSCs, possibly through increasing homing, survival, and/or self-renewal (Hoggatt et al. 2009, Hoggatt et al. 2013, North et al.).
DIFFERENTIATION
· Promotes differentiation of hematopoietic progenitor cells from mouse, macaque, and human embryonic stem cells (Gori et al., North et al., Woods et al.).
· Promotes differentiation of myeloid-derived suppressor cells from hematopoietic progenitors (Sinha et al.).
· Promotes differentiation of Th17 cells from naïve T-cells (Boniface et al.).
MAINTENANCE AND SELF-RENEWAL
· Required for the development of hematopoietic stem cells (HSCs) in mice and zebrafish (North et al.).
· Improves engraftment of mouse HSCs, possibly through increasing homing, survival, and/or self-renewal (Hoggatt et al. 2009, Hoggatt et al. 2013, North et al.).
DIFFERENTIATION
· Promotes differentiation of hematopoietic progenitor cells from mouse, macaque, and human embryonic stem cells (Gori et al., North et al., Woods et al.).
· Promotes differentiation of myeloid-derived suppressor cells from hematopoietic progenitors (Sinha et al.).
· Promotes differentiation of Th17 cells from naïve T-cells (Boniface et al.).
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Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Applications
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Resources and Publications
Educational Materials (3)
Publications (10)
Gut-Liver Physiomimetics Reveal Paradoxical Modulation of IBD-Related Inflammation by Short-Chain Fatty Acids. Cell systems 2020 mar
Abstract
Although the association between the microbiome and IBD and liver diseases is known, the cause and effect remain elusive. By connecting human microphysiological systems of the gut, liver, and circulating Treg and Th17 cells, we created a multi-organ model of ulcerative colitis (UC) ex vivo. The approach shows microbiome-derived short-chain fatty acids (SCFAs) to either improve or worsen UC severity, depending on the involvement of effector CD4 T cells. Using multiomics, we found SCFAs increased production of ketone bodies, glycolysis, and lipogenesis, while markedly reducing innate immune activation of the UC gut. However, during acute T cell-mediated inflammation, SCFAs exacerbated CD4+ T cell-effector function, partially through metabolic reprograming, leading to gut barrier disruption and hepatic injury. These paradoxical findings underscore the emerging utility of human physiomimetic technology in combination with systems immunology to study causality and the fundamental entanglement of immunity, metabolism, and tissue homeostasis.
Prostaglandin E2 enhances long-term repopulation but does not permanently alter inherent stem cell competitiveness. Blood 2013 OCT
Abstract
Hematopoietic stem cell (HSC) transplantation is a lifesaving therapy for malignant and nonmalignant hematologic diseases and metabolic disorders. Although successful, hematopoietic transplantation can be hindered by inadequate stem cell number or poor engrafting efficiency. To overcome these deficits, we and others have previously reported the HSC-enhancing ability of a short-term exposure of prostaglandin E2 (PGE2); this strategy has now progressed to phase 1 clinical trials in double cord blood transplantation. To further analyze the short- and long-term effects of HSC exposure to PGE2, we followed the repopulation kinetics of PGE2-treated hematopoietic grafts through 5 serial transplantations and compared inherent long-term competitiveness in a HSC head-to-head secondary transplantation model. Treatment with PGE2 did not result in a long-term increase in HSC competitiveness, lineage bias, or enhanced proliferative potential, demonstrating that pulse exposure to PGE2 results in transient increases in HSC homing and engraftment potential.
Efficient generation, purification, and expansion of CD34(+) hematopoietic progenitor cells from nonhuman primate-induced pluripotent stem cells. Blood 2012 SEP
Abstract
Induced pluripotent stem cell (iPSC) therapeutics are a promising treatment for genetic and infectious diseases. To assess engraftment, risk of neoplastic formation, and therapeutic benefit in an autologous setting, testing iPSC therapeutics in an appropriate model, such as the pigtail macaque (Macaca nemestrina; Mn), is crucial. Here, we developed a chemically defined, scalable, and reproducible specification protocol with bone morphogenetic protein 4, prostaglandin-E2 (PGE2), and StemRegenin 1 (SR1) for hematopoietic differentiation of Mn iPSCs. Sequential coculture with bone morphogenetic protein 4, PGE2, and SR1 led to robust Mn iPSC hematopoietic progenitor cell formation. The combination of PGE2 and SR1 increased CD34(+)CD38(-)Thy1(+)CD45RA(-)CD49f(+) cell yield by 6-fold. CD34(+)CD38(-)Thy1(+)CD45RA(-)CD49f(+) cells isolated on the basis of CD34 expression and cultured in SR1 expanded 3-fold and maintained this long-term repopulating HSC phenotype. Purified CD34(high) cells exhibited 4-fold greater hematopoietic colony-forming potential compared with unsorted hematopoietic progenitors and had bilineage differentiation potential. On the basis of these studies, we calculated the cell yields that must be achieved at each stage to meet a threshold CD34(+) cell dose that is required for engraftment in the pigtail macaque. Our protocol will support scale-up and testing of iPSC-derived CD34(high) cell therapies in a clinically relevant nonhuman primate model.
PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED.
