title: Ex vivo rapamycin treatment of human cord blood CD34+ cells enhances their engraftment of NSG mice.
abstract: Since cord blood (CB) has become a commonly used source of transplantable hematopoietic stem (HSC) and hematopoietic progenitor cells (HPC), there has been a need to overcome the limited HSC and HPC numbers available to transplant from a single CB, especially for adult recipients. Our laboratory previously demonstrated that Rheb2 overexpression significantly impaired the repopulating ability of HSC. Since overexpression of Rheb2 leads to increased signaling through mTOR, we examined the effect of the mTOR inhibitor rapamycin ex vivo on cytokine expanded CD34(+) CB cells for the engraftment of these cells in non-obese diabetic, severe combined immunodeficient, IL-2 receptor γ chain null (NSG) mice. We observed significant enhancement in engraftment of the CB treated ex vivo with cytokines in the presence of rapamycin prior to transplant, effects seen in primary as well as secondary transplants. These pre-clinical results suggest a positive role for rapamycin during ex vivo culture of CB SCID repopulating cells/HSC.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, 46202, USA.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Rohrabaugh
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Campbell
authors.forename: Giao
authors.initials: G
authors.lastname: Hangoc
authors.forename: Hal E
authors.initials: HE
authors.lastname: Broxmeyer
mesh_terms: D000818:Animals; D018952:Antigens, CD34; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005312:Fetal Blood / Q000187:drug effects*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents; D051379:Mice; D016513:Mice, SCID; D020123:Sirolimus / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018952:Antigens, CD34; D007166:Immunosuppressive Agents; D020123:Sirolimus