title: Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34(+) cells in NOD/SCID mice.
abstract: OBJECTIVE
  Mesenchymal stem cells (MSC) have been implicated as playing an important role in hematopoietic stem cell engraftment. We identified and characterized a new population of MSC derived from human fetal lung. In cotransplantation experiments, we examined the homing of MSC as well as the effect on engraftment of human umbilical cord blood (UCB)-derived CD34(+) cells in NOD/SCID mice.
  
  
  METHODS
  Culture-expanded fetal lung-derived CD34(+) cells were characterized by immune phenotyping and cultured under conditions promoting differentiation to osteoblasts or adipocytes. Irradiated (3.5 Gy) NOD/SCID mice (n = 51) were transplanted intravenously with 0.03 to 1.0 x 10(6) UCB CD34(+) cells in the presence or absence of 1 x 10(6) culture-expanded fetal lung-derived MSC, irradiated CD34(-) cells, B cells, or with cultured MSC only.
  
  
  RESULTS
  Culture-expanded fetal lung CD34(+) cells were identified as MSC based on phenotype (CD105(+), SH3(+), SH4(+), CD160(+)) and their multilineage potential. Cotransplantation of low doses of UCB CD34(+) cells and MSC resulted in a three-fold to four-fold increase in bone marrow engraftment after 6 weeks, whereas no such effect was observed after cotransplantation of irradiated CD34(-) or B cells. Homing experiments indicated the presence of MSC in the lung, but not in the bone marrow, of NOD/SCID mice.
  
  
  CONCLUSIONS
  We identified a population of MSC derived from human fetal lung. Upon cotransplantation, MSC, but not irradiated CD34(-) or B cells, promote engraftment of UCB CD34(+) cells in bone marrow, spleen, and blood by mechanisms that may not require homing of MSC to the bone marrow.
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden University Medical Center, The Netherlands. w.a.noort@lumc.nl
authors.forename: Willy A
authors.initials: WA
authors.lastname: Noort
authors.forename: Alwine B
authors.initials: AB
authors.lastname: Kruisselbrink
authors.forename: Pieternella S
authors.initials: PS
authors.lastname: in't Anker
authors.forename: Marjolein
authors.initials: M
authors.lastname: Kruger
authors.forename: Rutger L
authors.initials: RL
authors.lastname: van Bezooijen
authors.forename: Roelf A
authors.initials: RA
authors.lastname: de Paus
authors.forename: Mirjam H M
authors.initials: MH
authors.lastname: Heemskerk
authors.forename: Clemens W G M
authors.initials: CW
authors.lastname: Löwik
authors.forename: J H
authors.initials: JH
authors.lastname: Falkenburg
authors.forename: Roel
authors.initials: R
authors.lastname: Willemze
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D001402:B-Lymphocytes / Q000528:radiation effects; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology*; D016332:Fetal Tissue Transplantation; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000528:radiation effects; D006801:Humans; D008168:Lung / Q000166:cytology / Q000196:embryology; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009928:Organ Specificity; D010006:Osteoblasts / Q000166:cytology; D011828:Radiation Chimera; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology; D014183:Transplantation, Heterologous
chemical_list: D016207:Cytokines