Mesenchymal stromal cells from Shwachman-Diamond syndrome patients fail to recreate a bone marrow niche in vivo and exhibit impaired angiogenesis

British Journal of Haematology
Donatella BardelliGiovanna D'amico

Abstract

Shwachman-Diamond syndrome (SDS) is a rare multi-organ recessive disease mainly characterised by pancreatic insufficiency, skeletal defects, short stature and bone marrow failure (BMF). As in many other BMF syndromes, SDS patients are predisposed to develop a number of haematopoietic malignancies, particularly myelodysplastic syndrome and acute myeloid leukaemia. However, the mechanism of cancer predisposition in SDS patients is only partially understood. In light of the emerging role of mesenchymal stromal cells (MSCs) in the regulation of bone marrow homeostasis, we assessed the ability of MSCs derived from SDS patients (SDS-MSCs) to recreate a functional bone marrow niche, taking advantage of a murine heterotopic MSC transplant model. We show that the ability of semi-cartilaginous pellets (SCPs) derived from SDS-MSCs to generate complete heterotopic ossicles in vivo is severely impaired in comparison with HD-MSC-derived SCPs. Specifically, after in vitro angiogenic stimuli, SDS-MSCs showed a defective ability to form correct networks, capillary tubes and vessels and displayed a marked decrease in VEGFA expression. Altogether, these findings unveil a novel mechanism of SDS-mediated haematopoietic dysfunction based on hampered...Continue Reading

References

Jan 12, 1999·The Journal of Clinical Investigation·P J Newman
Dec 24, 2002·Nature Genetics·Graeme R B BoocockJohanna M Rommens
Jul 28, 2005·Pediatric Blood & Cancer·Yigal Dror
May 10, 2006·British Journal of Haematology·Elaine W LeungYigal Dror
Mar 23, 2010·Nature·Marc H G P RaaijmakersDavid T Scadden
May 30, 2012·Laboratory Investigation; a Journal of Technical Methods and Pathology·Dong-Feng NiuRyohei Katoh
Nov 6, 2013·Journal of Cellular and Molecular Medicine·Nicolas EspagnollePhilippe Bourin
Oct 16, 2015·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·William B StallcupFusanori Yotsumoto
Feb 13, 2016·Frontiers in Cellular Neuroscience·Andrea TrostHerbert A Reitsamer

❮ Previous
Next ❯

Related Concepts

Related Feeds

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

Related Papers

Anales de pediatría : publicación oficial de la Asociación Española de Pediatría (A.E.P.)
R Maria Macipe CostaMaria T Calvo Martín
[Rinshō ketsueki] The Japanese journal of clinical hematology
M YaguchiK Toriyama
© 2022 Meta ULC. All rights reserved