Mesenchymal Stem Cells, Fibroblasts and Pericytes: Different Functional States of the Same Cell?.

Mesenchymal stem cells (MSC) are multipotent precursors present in the bone marrow (BM), capable of differentiating into osteoblasts, adipocytes, chondrocytes and myoblasts. In addition to BM, MSC can be obtained from a variety of adult and fetal tissues. Additionally pericytes, that form a continuous subendothelial network of the vascular bed, share many properties with MSC, whereas the name stromal cell or fibroblast is often used interchangeably with MSC. How similar are MSCs obtained from different human tissues and what is their relationship with fibroblasts and pericytes? To answer these questions we have examined the expression of a set of 30 genes in 18 different human cell lines cultured in vitro: 7 MSC cultures from different sources (3 adult tissues: bone marrow, saphena vein, adipose tissue, and 4 fetal tissues: artery, liver, umbilical artery and umbilical vein), 2 of fibroblasts, 2 MSC cultures differentiated in vitro into adipocytes or osteoblasts, and one each of pericytes from the human retina, of bone marrow, endothelial cells, liver, brain, skeletal muscle and heart. Genes were selected on the basis of previous results of SAGE for MSC, CD34⁺ cells and fibroblasts. Cluster analysis using the software Cluster 3.0 UPGMA (average linkage) showed that all the MSC lines formed a very close cluster with pericytes and fibroblasts, separated from other normal human cells. Changes of the expression of highly expressed MSC genes were modest during in vitro differentiation of MSCs into osteoblasts or adipocytes, although the differentiation was accompanied by the increased expression of tissue specific genes. In addition, all the MSC lines had similar immunophenotypic markers and capacity for in vitro differentiation. Similarity of the gene expression profiles of MSC and fibrobasts were further confirmed by clustering of the 1,000 top expressed tags of SAGE libraries for 21 normal human tissues. Despite the similarity, expression of genes related to angiogenesis, especially CXCL6, was higher in MSC from umbilical vein, adult saphena vein and in pericytes than in BM-derived MSC. In conclusion, MSC that can be obtained from a variety of adult and fetal tissues have very similar biological markers, differentiation potential and gene expression profiles. Comparison of these characteristics also shows that MSC, fibroblasts and pericytes are very closely related, representing probably different functional states of the same cell. Finally, differentiaton of MSC into osteoblasts or adipocytes is marked by the expression of tissue specific genes, without dramatical changes of the overall profile.