Oncotarget

Research Papers:

Severe hypoxia selects hematopoietic progenitors with stem cell potential from primary Myelodysplastic syndrome bone marrow cell cultures

Erico Masala, Ana Valencia-Martinez, Serena Pillozzi, Tommaso Rondelli, Alice Brogi, Alessandro Sanna, Antonella Gozzini, Annarosa Arcangeli, Persio Dello Sbarba and Valeria Santini _

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Oncotarget. 2018; 9:10561-10571. https://doi.org/10.18632/oncotarget.24302

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Abstract

Erico Masala1, Ana Valencia-Martinez1, Serena Pillozzi2, Tommaso Rondelli3, Alice Brogi1,5, Alessandro Sanna1, Antonella Gozzini4, Annarosa Arcangeli2, Persio Dello Sbarba6 and Valeria Santini1

1MDS UNIT, Hematology, AOU-Careggi University Hospital, Department of Experimental and Clinical Medicine, Università degli Studi di Firenze, Florence, Italy

2Department of Experimental and Clinical Medicine, Università degli Studi di Firenze, Florence, Italy

3General Laboratory, AOU-Careggi, Florence, Italy

4Cellular Therapy and Transfusional Medicine Unit, Hematology, AOU-Careggi University Hospital, Florence, Italy

5Department of Medical Biotechnologies, Università degli Studi di Siena, Siena, Italy

6Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, Università degli Studi di Firenze, Florence, Italy

Correspondence to:

Valeria Santini, email: valeria.santini@unifi.it

Persio Dello Sbarba, email: persio@unifi.it

Keywords: MDS; stem cells; hypoxia; high risk MDS; mice transplantation

Received: December 22, 2016     Accepted: January 13, 2018     Published: January 24, 2018

ABSTRACT

Myelodysplastic Syndromes (MDS) are clonal neoplasms where stem/progenitor cells endowed with self-renewal and capable of perpetuating the disease have been demonstrated. It is known that oxygen tension plays a key role in driving normal hematopoiesis and that hematopoietic stem cells are maintained in hypoxic areas of the bone marrow (BM). Hypoxia could also regulate leukemic/dysplastic hematopoiesis. We evaluated the stem cell potential of MDS cells derived from the BM of 39 MDS patients and selected under severe hypoxia. MDS cells rescued from hypoxia-incubated cultures were subjected to stem and progenitor cell assays in vitro, as well as to hematopoietic reconstitution assay in NOD-SCID mice. Incubation in severe hypoxia of cells explanted from MDS patients selected a cell subset endowed with stem cell potential, as determined in vitro. This occurred only from the BM of patients classified as IPSS low/INT-1 risk. Transplantation into NOD-SCID mice confirmed using an in vivo model that severe hypoxia selects a cell subset endowed with stem cell potential from bone marrow mononuclear cells (BMMC). derived from patients belonging to the IPSS low/int-1 risk group. Data here reported show that cells endowed with stem cell potential and capable of adapting to hypoxia and escaping hypoxia-induced apoptosis exist within MDS cell populations.


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