title: Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential.
abstract: 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.
authors.affiliation: Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Pieternella S
authors.initials: PS
authors.lastname: in 't Anker
authors.forename: Willy A
authors.initials: WA
authors.lastname: Noort
authors.forename: Sicco A
authors.initials: SA
authors.lastname: Scherjon
authors.forename: Carin
authors.initials: C
authors.lastname: Kleijburg-van der Keur
authors.forename: Alwine B
authors.initials: AB
authors.lastname: Kruisselbrink
authors.forename: Rutger L
authors.initials: RL
authors.lastname: van Bezooijen
authors.forename: Willem
authors.initials: W
authors.lastname: Beekhuizen
authors.forename: Roelof
authors.initials: R
authors.lastname: Willemze
authors.forename: Humphrey H H
authors.initials: HH
authors.lastname: Kanhai
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
mesh_terms: 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
chemical_list: D018952:Antigens, CD34