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


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.


CONCLUSIONS
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.
Covas
Dimas T
DT
Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil. dimas@fmrp.usp.br
Panepucci
Rodrigo A
RA
Fontes
Aparecida M
AM
Silva
Wilson A
WA
Orellana
Maristela D
MD
Freitas
Marcela C C
MC
Neder
Luciano
L
Santos
Anemari R D
AR
Peres
Luiz C
LC
Jamur
Maria C
MC
Zago
Marco A
MA
D051929:CD146 Antigen / Q000235:genetics* / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D016000:Cluster Analysis; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D020286:Pericytes / Q000166:cytology* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics; D014470:Umbilical Cord / Q000166:cytology* / Q000502:physiology
D051929:CD146 Antigen