title: Maitake beta-glucan enhances umbilical cord blood stem cell transplantation in the NOD/SCID mouse.
abstract: Beta glucans are cell wall constituents of yeast, fungi and bacteria, as well as mushrooms and barley. Glucans are not expressed on mammalian cells and are recognized as pathogen-associated molecular patterns (PAMPS) by pattern recognition receptors (PRR). Beta glucans have potential activity as biological response modifiers for hematopoiesis and enhancement of bone marrow recovery after injury. We have reported that Maitake beta glucan (MBG) enhanced mouse bone marrow (BMC) and human umbilical cord blood (CB) cell granulocyte-monocyte colony forming unit (GM-CFU) activity in vitro and protected GM-CFU forming stem cells from doxorubicin (DOX) toxicity. The objective of this study was to determine the effects of MBG on expansion of phenotypically distinct subpopulations of progenitor and stem cells in CB from full-term infants cultured ex vivo and on homing and engraftment in vivo in the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse. MBG promoted a greater expansion of CD34+CD33+CD38- human committed hematopoietic progenitor (HPC) cells compared to the conventional stem cell culture medium (P = 0.002 by ANOVA). CD34+CXCR4+CD38- early, uncommitted human hematopoietic stem cell (HSC) numbers showed a trend towards increase in response to MBG. The fate of CD34+ enriched CB cells after injection into the sublethally irradiated NOS/SCID mouse was evaluated after retrieval of xenografted human CB from marrow and spleen by flow cytometric analysis. Oral administration of MBG to recipient NOS/SCID mice led to enhanced homing at 3 days and engraftment at 6 days in mouse bone marrow (P = 0.002 and P = 0.0005, respectively) compared to control mice. More CD34+ human CB cells were also retrieved from mouse spleen in MBG treated mice at 6 days after transplantation. The studies suggest that MBG promotes hematopoiesis through effects on CD34+ progenitor cell expansion ex vivo and when given to the transplant recipient could enhance CD34+ precursor cell homing and support engraftment.
authors.affiliation: Department of Pediatrics, Cornell University Weill Medical College, 1300 York Avenue, New York, NY 10021, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Lin
authors.forename: Elisa
authors.initials: E
authors.lastname: De Stanchina
authors.forename: Xi Kathy
authors.initials: XK
authors.lastname: Zhou
authors.forename: Yuhong
authors.initials: Y
authors.lastname: She
authors.forename: Danthanh
authors.initials: D
authors.lastname: Hoang
authors.forename: Sandy Wy
authors.initials: SW
authors.lastname: Cheung
authors.forename: Barrie
authors.initials: B
authors.lastname: Cassileth
authors.forename: Susanna
authors.initials: S
authors.lastname: Cunningham-Rundles
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D036101:Cord Blood Stem Cell Transplantation; D005312:Fetal Blood / Q000166:cytology; D048691:Grifola / Q000737:chemistry*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009419:Nerve Tissue Proteins / Q000378:metabolism; D047071:beta-Glucans / Q000494:pharmacology*; D000099181:Dectin-1
chemical_list: D018952:Antigens, CD34; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D047071:beta-Glucans; D000099181:Dectin-1