title: Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models.
abstract: Hematopoietic stem cells (HSCs) are used in transplantation therapy to reconstitute the hematopoietic system. Human cord blood (hCB) transplantation has emerged as an attractive alternative treatment option when traditional HSC sources are unavailable; however, the absolute number of hCB HSCs transplanted is significantly lower than bone marrow or mobilized peripheral blood stem cells (MPBSCs). We previously demonstrated that dimethyl-prostaglandin E2 (dmPGE2) increased HSCs in vertebrate models. Here, we describe preclinical analyses of the therapeutic potential of dmPGE2 treatment by using human and nonhuman primate HSCs. dmPGE2 significantly increased total human hematopoietic colony formation in vitro and enhanced engraftment of unfractionated and CD34(+) hCB after xenotransplantation. In nonhuman primate autologous transplantation, dmPGE2-treated CD34(+) MPBSCs showed stable multilineage engraftment over 1 year postinfusion. Together, our analyses indicated that dmPGE2 mediates conserved responses in HSCs from human and nonhuman primates and provided sufficient preclinical information to support proceeding to an FDA-approved phase 1 clinical trial.
authors.affiliation: Genetics and Gastroenterology Divisions, Brigham and Women's Hospital, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Goessling
authors.forename: Robyn S
authors.initials: RS
authors.lastname: Allen
authors.forename: Xiao
authors.initials: X
authors.lastname: Guan
authors.forename: Ping
authors.initials: P
authors.lastname: Jin
authors.forename: Naoya
authors.initials: N
authors.lastname: Uchida
authors.forename: Michael
authors.initials: M
authors.lastname: Dovey
authors.forename: James M
authors.initials: JM
authors.lastname: Harris
authors.forename: Mark E
authors.initials: ME
authors.lastname: Metzger
authors.forename: Aylin C
authors.initials: AC
authors.lastname: Bonifacino
authors.forename: David
authors.initials: D
authors.lastname: Stroncek
authors.forename: Joseph
authors.initials: J
authors.lastname: Stegner
authors.forename: Myriam
authors.initials: M
authors.lastname: Armant
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlaeger
authors.forename: John F
authors.initials: JF
authors.lastname: Tisdale
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Zon
authors.forename: Robert E
authors.initials: RE
authors.lastname: Donahue
authors.forename: Trista E
authors.initials: TE
authors.lastname: North
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D003114:Colony-Forming Units Assay; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology*; D006085:Graft Survival; D006801:Humans; D023421:Models, Animal; D011323:Primates; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34; D015232:Dinoprostone