Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro

F. G.J. Calkoen, C. Vervat, M. van Pel, V. de Haas, L. Vijfhuizen, E. Eising, W. G.M. Kroes, P. A.C. 't Hoen, M. M. van den Heuvel-Eibrink, R. M. Egeler, M. J.D. van Tol, L. M. Ball

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

14 Citaten (Scopus)

Samenvatting

Pediatric myelodysplastic syndrome (MDS) is a heterogeneous disease covering a spectrum ranging from aplasia (RCC) to myeloproliferation (RAEB(t)). In adult-type MDS there is increasing evidence for abnormal function of the bone-marrow microenvironment. Here, we extensively studied the mesenchymal stromal cells (MSCs) derived from children with MDS. MSCs were expanded from the bone-marrow of 17 MDS patients (RCC: n = 10 and advanced MDS: n = 7) and pediatric controls (n = 10). No differences were observed with respect to phenotype, differentiation capacity, immunomodulatory capacity or hematopoietic support. mRNA expression analysis by Deep-SAGE revealed increased IL-6 expression in RCC- and RAEB(t)-MDS. RCC-MDS MSC expressed increased levels of DKK3, a protein associated with decreased apoptosis. RAEB(t)-MDS revealed increased CRLF1 and decreased DAPK1 expressions. This pattern has been associated with transformation in hematopoietic malignancies. Genes reported to be differentially expressed in adult MDS-MSC did not differ between MSC of pediatric MDS and controls.An altered mRNA expression profile, associated with cell survival and malignant transformation, of MSC derived from children with MDS strengthens the hypothesis that the micro-environment is of importance in this disease. Our data support the understanding that pediatric and adult MDS are two different diseases. Further evaluation of the pathways involved might reveal additional therapy targets.

Originele taal-2Engels
Pagina's (van-tot)198-210
Aantal pagina's13
TijdschriftStem Cell Research
Volume14
Nummer van het tijdschrift2
DOI's
StatusGepubliceerd - 1 mrt. 2015
Extern gepubliceerdJa

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