Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34(+) cells in NOD/SCID mice.
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.
Noort
Willy A
WA
Department of Hematology, Leiden University Medical Center, Leiden University Medical Center, The Netherlands. w.a.noort@lumc.nl
Kruisselbrink
Alwine B
AB
in't Anker
Pieternella S
PS
Kruger
Marjolein
M
van Bezooijen
Rutger L
RL
de Paus
Roelf A
RA
Heemskerk
Mirjam H M
MH
Löwik
Clemens W G M
CW
Falkenburg
J H
JH
Willemze
Roel
R
Fibbe
Willem E
WE
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
D016207:Cytokines