Shwachman-Diamond syndrome (SDS) is a rare inherited disorder characterized by bone marrow (BM) dysfunction and exocrine pancreatic insufficiency. SDS patients have an increased risk for myelodisplastic syndrome and acute myeloid leukemia. Mesenchymal stem cells (MSCs) are the key component of the hematopoietic microenvironment and are relevant in inducing genetic mutations leading to leukemia. However, their role in SDS is still unexplored. We demonstrated that morphology, growth kinetics and expression of surface markers of MSCs from SDS patients (SDS-MSCs) were similar to normal MSCs. Moreover, SDS-MSCs were able to differentiate into mesengenic lineages and to inhibit the proliferation of mitogen-activated lymphocytes. We demonstrated in an in vitro coculture system that SDS-MSCs, significantly inhibited neutrophil apoptosis probably through interleukin-6 production. In a long-term coculture with CD34+-sorted cells, SDS-MSCs were able to sustain CD34+ cells survival and to preserve their stemness. Finally, SDS-MSCs had normal karyotype and did not show any chromosomal abnormality observed in the hematological components of the BM of SDS patients. Despite their pivotal role in the hematopoietic stem cell niche, our data suggest that MSC themselves do not seem to be responsible for the hematological defects typical of SDS patients. © 2012 Macmillan Publishers Limited All rights reserved.

André, V., Longoni, D., Bresolin, S., Cappuzzello, C., Dander, E., Galbiati, M., et al. (2012). Mesenchymal stem cells from Shwachman-Diamond syndrome patients display normal functions and do not contribute to hematological defects. BLOOD CANCER JOURNAL, 2(10) [10.1038/bcj.2012.40].

Mesenchymal stem cells from Shwachman-Diamond syndrome patients display normal functions and do not contribute to hematological defects

CAPPUZZELLO, CLAUDIA;DANDER, ERICA;Serafini, M;Cazzaniga, G;BIONDI, ANDREA;
2012

Abstract

Shwachman-Diamond syndrome (SDS) is a rare inherited disorder characterized by bone marrow (BM) dysfunction and exocrine pancreatic insufficiency. SDS patients have an increased risk for myelodisplastic syndrome and acute myeloid leukemia. Mesenchymal stem cells (MSCs) are the key component of the hematopoietic microenvironment and are relevant in inducing genetic mutations leading to leukemia. However, their role in SDS is still unexplored. We demonstrated that morphology, growth kinetics and expression of surface markers of MSCs from SDS patients (SDS-MSCs) were similar to normal MSCs. Moreover, SDS-MSCs were able to differentiate into mesengenic lineages and to inhibit the proliferation of mitogen-activated lymphocytes. We demonstrated in an in vitro coculture system that SDS-MSCs, significantly inhibited neutrophil apoptosis probably through interleukin-6 production. In a long-term coculture with CD34+-sorted cells, SDS-MSCs were able to sustain CD34+ cells survival and to preserve their stemness. Finally, SDS-MSCs had normal karyotype and did not show any chromosomal abnormality observed in the hematological components of the BM of SDS patients. Despite their pivotal role in the hematopoietic stem cell niche, our data suggest that MSC themselves do not seem to be responsible for the hematological defects typical of SDS patients. © 2012 Macmillan Publishers Limited All rights reserved.
Articolo in rivista - Articolo scientifico
Mesenchymal stem cells, Shwachman-Diamond syndrome, hematological defects
English
2012
2
10
e94
none
André, V., Longoni, D., Bresolin, S., Cappuzzello, C., Dander, E., Galbiati, M., et al. (2012). Mesenchymal stem cells from Shwachman-Diamond syndrome patients display normal functions and do not contribute to hematological defects. BLOOD CANCER JOURNAL, 2(10) [10.1038/bcj.2012.40].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/50118
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