Collection of Samples of Bone Marrow Aspiration From Patients With Myelodysplastic Syndrome

Mitochondrial dysfunction is often associated with MDS. Studies have shown mitochondrial DNA (mtDNA) mutations in different MDS subtypes; however, their role in the pathogenesis and disease progression are not yet clear. Point mutations were found in various locations in the mitochondrial genome including tRNAs, rRNAs, and mitochondrial proteins.

Mitochondrial fragmentation in hematopoietic stem and progenitor cells (HSPC) can lead to ineffective hematopoiesis in MDS, suggesting mitochondria as a therapeutic target for treating MDS.

Mitochondria augmentation therapy (MAT) is a novel cell technology where hematopoietic stem and progenitor cells (HSPCs) are augmented ex vivo with mitochondria obtained from donor cells or tissue. MAT is based on the demonstrated ability of isolated mitochondria to enter cells and impact mitochondrial function and metabolic activity in the recipient cells. The transfer of mitochondria from cell to cell has been demonstrated using extracellular vesicles, nanotubes, and micropinocytosis. Mitochondria entering cells provide copies of normal mtDNA, which can be further propagated via replication within the recipient cell and via intercellular transfer.

Research will include in vitro and in vivo studies with the bone marrow sample, including, among other, the following: mitochondrial augmentation of bone marrow aspiration and/or subpopulations of cells (e.g. CD34+) isolated from the bone marrow aspiration; differentiation of augmented and/or non-augmented bone marrow aspiration and/or subpopulations of cells into hematopoietic lineages (e.g. erythroid, megakaryocyte, etc); assays of mitochondrial content and function; assays of hematopoietic lineages; culture of augmented and/or non-augmented bone marrow aspiration and/or subpopulations; cryopreservation of augmented and/or non-augmented bone marrow aspiration and/or subpopulations; sequencing of mitochondrial DNA and nuclear DNA; in vivo studies of engraftment, biodistribution and function of augmented and/or non-augmented bone marrow aspiration and/or subpopulations of cells isolated from the bone marrow aspiration.

Research will include in vitro studies with the peripheral blood sample, including, among other, the following: immunophenotyping of peripheral blood cells and immune-related functional assays; mitochondrial content and function of peripheral blood cells.

Inclusion criteria

• Male or female patients of 18 years old and up.
• Suspected or previously diagnosed with Myelodysplastic Syndrome.
• Patient able to understand and provide voluntary written informed consent.

Exclusion criteria

• History of prior allogeneic hematopoietic stem cell transplantation, cell therapy, gene therapy.