Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146+ perivascular cells and fibroblasts

Covas, Dimas T.; Panepucci, Rodrigo A.; Fontes, Aparecida M.; Silva, Wilson A.; Orellana, Maristela D.; Freitas, Marcela C.C.; Neder, Luciano; Santos, Anemari R.D.; Peres, Luiz C.; Jamur, Maria C.; Zago, Marco A.

doi:10.1016/j.exphem.2007.12.015

« Previous Next »Experimental Hematology
Volume 36, Issue 5 , Pages 642-654, May 2008

Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146⁺ perivascular cells and fibroblasts

Dimas T. Covas
- Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil
- Offprint requests to: Dimas T. Covas, M.D., Ph.D., Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Hemocentro, R. Tenente Catão Roxo, 2501, 14051-140 Ribeirão Preto, Brazil
Rodrigo A. Panepucci
- Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil
Aparecida M. Fontes
- Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil
Wilson A. Silva Jr.
- Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil
- Department of Genetics of Faculty of Medicine, University of São Paulo, Ribeirão Preto, Brazil
Maristela D. Orellana
- Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil
Marcela C.C. Freitas
- Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil
Luciano Neder
- Department of Pathology, University of São Paulo, Ribeirão Preto, Brazil
Anemari R.D. Santos
- Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil
Luiz C. Peres
- Department of Pathology, University of São Paulo, Ribeirão Preto, Brazil
Maria C. Jamur
- Department of Cell and Molecular Biology, University of São Paulo, Ribeirão Preto, Brazil
Marco A. Zago
- Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil

Received 17 December 2007; received in revised form 17 December 2007; accepted 21 December 2007. published online 27 February 2008.

Objective

The relationship of multipotent mesenchymal stromal cells (MSC) with pericytes and fibroblasts has not been established thus far, although they share many markers of primitive marrow stromal cells and the osteogenic, adipogenic, and chondrogenic differentiation potentials.

Materials and Methods

We compared MSCs from adult or fetal tissues, MSC differentiated in vitro, fibroblasts and cultures of retinal pericytes obtained either by separation with anti-CD146 or adhesion. The characterizations included morphological, immunophenotypic, gene-expression profile, and differentiation potential.

Results

Osteogenic, adipocytic, and chondrocytic differentiation was demonstrated for MSC, retinal perivascular cells, and fibroblasts. Cell morphology and the phenotypes defined by 22 markers were very similar. Analysis of the global gene expression obtained by serial analysis of gene expression for 17 libraries and by reverse transcription polymerase chain reaction of 39 selected genes from 31 different cell cultures, revealed similarities among MSC, retinal perivascular cells, and hepatic stellate cells. Despite this overall similarity, there was a heterogeneous expression of genes related to angiogenesis, in MSC derived from veins, artery, perivascular cells, and fibroblasts. Evaluation of typical pericyte and MSC transcripts, such as NG2, CD146, CD271, and CD140B on CD146 selected perivascular cells and MSC by real-time polymerase chain reaction confirm the relationship between these two cell types. Furthermore, the inverse correlation between fibroblast-specific protein-1 and CD146 transcripts observed on pericytes, MSC, and fibroblasts highlight their potential use as markers of this differentiation pathway.

Conclusion

Our results indicate that human MSC and pericytes are similar cells located in the wall of the vasculature, where they function as cell sources for repair and tissue maintenance, whereas fibroblasts are more differentiated cells with more restricted differentiation potential.