Identification of cord blood-derived mesenchyrnal stem/stromal cell populations with distinct growth kinetics, differentiation potentials, and gene expression profiles

被引:76
作者
Markov, Vladimir
Kusumi, Kenro
Tadesse, Mahlet G.
William, Dilusha A.
Hall, Dorian M.
Lounev, Vitali
Carlton, Arlene
Leonard, Jay
Cohen, Rick I.
Rappaport, Eric F.
Saitta, Biagio [1 ]
机构
[1] Coriell Inst Med Res, Lab Stem Cell & Matrix Biol, Camden, NJ 08103 USA
[2] Univ Penn, Childrens Hosp Philadelphia, Div Human Genet, Sch Med, Philadelphia, PA 19104 USA
[3] Univ Penn, Div Orthopaed Surg, Sch Med, Philadelphia, PA 19104 USA
[4] Univ Penn, Dept Pediat, Sch Med, Philadelphia, PA 19104 USA
[5] Univ Penn, Dept Cell & Dev Biol, Sch Med, Philadelphia, PA 19104 USA
[6] Univ Arizona, Sch Life Sci, Phoenix, AZ 85287 USA
[7] Univ Arizona, Coll Med, Dept Basic Med Sci, Phoenix, AZ 85004 USA
[8] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA
[9] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, Camden, NJ 08103 USA
关键词
D O I
10.1089/scd.2006.0660
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Phenotypic heterogeneity has been observed among mesenchymal stem/stromal cell (MSC) populations, but specific genes associated with this variability have not been defined. To study this question, we analyzed two distinct isogenic MSC populations isolated from umbilical cord blood (UCB1 and UCB2). The use of isogenic populations eliminated differences contributed by genetic background. We characterized these UCB MSCs for cell morphology, growth kinetics, immunophenotype, and potential for differentiation. UCB1 displayed faster growth kinetics, higher population doublings, and increased adipogenic lineage differentiation compared to UCB2. However, osteogenic differentiation was stronger for the UCB2 population. To identify MSC-specific genes and developmental genes associated with observed phenotypic differences, we performed expression analysis using Affymetrix microarrays and compared them to bone marrow (BM) MSCs. We compared UCB1, UCB2, and BM and identified distinct gene expression patterns. Selected clusters were analyzed demonstrating that genes of multiple developmental pathways, such as transforming growth factor-beta (TGF-beta) and wnt genes, and markers of early embryonic stages and mesodermal differentiation displayed significant differences among the MSC populations. In undifferentiated UCB1 cells, multiple genes were significantly up-regulated (p < 0.0001): peroxisome proliferation activated receptor gamma (PPARG), which correlated with adipogenic differentiation capacities, hepatocyte growth factor (HGF), and stromal-derived factor 1 (SDF1/CXCL12), which could both potentially contribute to the higher growth kinetics observed in UCB1 cells. Overall, the results confirmed the presence of two distinct isogenic UCB-derived cell populations, identified gene profiles useful to distinguish MSC types with different lineage differentiation potentials, and helped clarify the heterogeneity observed in these cells.
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页码:53 / 73
页数:21
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