Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential.
OBJECTIVE
We previously found that human fetal lung is a rich source of mesenchymal stem cells (MSC). Here we characterize and analyze the frequency and function of MSC in other second-trimester fetal tissues.


METHODS
Single cell suspensions of fetal bone marrow (BM), liver, lung, and spleen were made and analyzed by flow cytometry for the expression of CD90, CD105, CD166, SH3, SH4, HLA-ABC, HLA-DR, CD34 and CD45. We assessed the frequency of MSC by limiting dilution assay.


RESULTS
The frequency of MSC in BM was significantly higher than in liver, lung, and spleen (p<0.05). On primary non-expanded cells from fetal liver, lung and spleen the number of cells positive for mesenchymal markers was significantly higher within the CD34 positive population than within the CD34 negative population. The phenotype of the culture-expanded MSC was similar for all fetal tissues, i.e. CD90, CD105, CD166, SH3, SH4 and HLA-ABC positive and CD34, CD45 and HLA-DR negative. Culture-expanded cells from all tissues were able to differentiate along adipogenic and osteogenic pathways. However, adipogenic differentiation was less in MSC derived from spleen, and osteogenic differentiation was reduced in liver-derived MSC (p<0.05).


CONCLUSIONS
Our results indicate that culture-expanded MSC derived from second-trimester fetal tissues, although phenotypically similar, exhibit heterogeneity in differentiating potential. We speculate that these differences may be relevant for the clinical application of MSC.
in 't Anker
Pieternella S
PS
Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands.
Noort
Willy A
WA
Scherjon
Sicco A
SA
Kleijburg-van der Keur
Carin
C
Kruisselbrink
Alwine B
AB
van Bezooijen
Rutger L
RL
Beekhuizen
Willem
W
Willemze
Roelof
R
Kanhai
Humphrey H H
HH
Fibbe
Willem E
WE
D000029:Abortion, Legal; D017667:Adipocytes / Q000737:chemistry / Q000145:classification / Q000166:cytology / Q000378:metabolism; D018952:Antigens, CD34 / Q000032:analysis / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005333:Fetus / Q000166:cytology; D006098:Granulocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D008099:Liver / Q000166:cytology* / Q000196:embryology; D008168:Lung / Q000166:cytology* / Q000196:embryology; D008214:Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D008648:Mesoderm / Q000145:classification / Q000166:cytology*; D009000:Monocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000145:classification / Q000166:cytology*; D010011:Osteocytes / Q000737:chemistry / Q000145:classification / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D013154:Spleen / Q000166:cytology* / Q000196:embryology
D018952:Antigens, CD34