scholarly journals PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem and progenitor cells

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Linda Varagnolo ◽  
Qiong Lin ◽  
Nadine Obier ◽  
Christoph Plass ◽  
Johannes Dietl ◽  
...  
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

scholarly journals Engineering of fully humanized and vascularized 3D bone marrow niches sustaining undifferentiated human cord blood hematopoietic stem and progenitor cells

2021 ◽  
Vol 12 ◽  
pp. 204173142110448
Author(s):  
Gordian Born ◽  
Marina Nikolova ◽  
Arnaud Scherberich ◽  
Barbara Treutlein ◽  
Andrés García-García ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Progenitor Cells ◽  
Stromal Vascular Fraction ◽  
Human Adipose Tissue ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
A Cell ◽  
Modular Platform

Hematopoietic stem and progenitor cells (HSPCs) are frequently located around the bone marrow (BM) vasculature. These so-called perivascular niches regulate HSC function both in health and disease, but they have been poorly studied in humans due to the scarcity of models integrating complete human vascular structures. Herein, we propose the stromal vascular fraction (SVF) derived from human adipose tissue as a cell source to vascularize 3D osteoblastic BM niches engineered in perfusion bioreactors. We show that SVF cells form self-assembled capillary structures, composed by endothelial and perivascular cells, that add to the osteogenic matrix secreted by BM mesenchymal stromal cells in these engineered niches. In comparison to avascular osteoblastic niches, vascularized BM niches better maintain immunophenotypically-defined cord blood (CB) HSCs without affecting cell proliferation. In contrast, HSPCs cultured in vascularized BM niches showed increased CFU-granulocyte-erythrocyte-monocyte-megakaryocyte (CFU-GEMM) numbers. The vascularization also contributed to better preserve osteogenic gene expression in the niche, demonstrating that niche vascularization has an influence on both hematopoietic and stromal compartments. In summary, we have engineered a fully humanized and vascularized 3D BM tissue to model native human endosteal perivascular niches and revealed functional implications of this vascularization in sustaining undifferentiated CB HSPCs. This system provides a unique modular platform to explore hemato-vascular interactions in human healthy/pathological hematopoiesis.

scholarly journals Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Annette Audigé ◽  
Mary-Aude Rochat ◽  
Duo Li ◽  
Sandra Ivic ◽  
Audrey Fahrny ◽  
...  
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
Nsg Mice ◽  
Stem And Progenitor Cells

scholarly journals Only Hematopoietic Stem and Progenitor Cells from Cord Blood Are Susceptible to Malignant Transformation by MLL-AF4 Translocations

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1487
Author(s):  
Kathy-Ann Secker ◽  
Lukas Bruns ◽  
Hildegard Keppeler ◽  
Johan Jeong ◽  
Thomas Hentrich ◽  
...  
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Growth Potential ◽  
Fusion Partner ◽  
Cell Of Origin ◽  
Human Cord Blood ◽  
Lymphoid Leukemia ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
The Impact

Mixed lineage leukemia (MLL) (KMT2A) rearrangements (KMT2Ar) play a crucial role in leukemogenesis. Dependent on age, major differences exist regarding disease frequency, main fusion partners and prognosis. In infants, up to 80% of acute lymphoid leukemia (ALL) bear a MLL translocation and half of them are t(4;11), resulting in a poor prognosis. In contrast, in adults only 10% of acute myeloid leukemia (AML) bear t(9;11) with an intermediate prognosis. The reasons for these differences are poorly understood. Recently, we established an efficient CRISPR/Cas9-based KMT2Ar model in hematopoietic stem and progenitor cells (HSPCs) derived from human cord blood (huCB) and faithfully mimicked the underlying biology of the disease. Here, we applied this model to HSPCs from adult bone marrow (huBM) to investigate the impact of the cell of origin and fusion partner on disease development. Both genome-edited infant and adult KMT2Ar cells showed monoclonal outgrowth with an immature morphology, myelomonocytic phenotype and elevated KMT2Ar target gene expression comparable to patient cells. Strikingly, all KMT2Ar cells presented with indefinite growth potential except for MLL-AF4 huBM cells ceasing proliferation after 80 days. We uncovered FFAR2, an epigenetic tumor suppressor, as potentially responsible for the inability of MLL-AF4 to immortalize adult cells under myeloid conditions.

scholarly journals Development of a vascular niche platform for expansion of repopulating human cord blood stem and progenitor cells

Blood ◽  
2012 ◽  
Vol 120 (6) ◽  
pp. 1344-1347 ◽  
Author(s):  
Jason M. Butler ◽  
Eric J. Gars ◽  
Daylon J. James ◽  
Daniel J. Nolan ◽  
Joseph M. Scandura ◽  
...  
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Culture Conditions ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Cord Blood Cells

Abstract Transplantation of ex vivo expanded human umbilical cord blood cells (hCB) only partially enhances the hematopoietic recovery after myelosuppressive therapy. Incubation of hCB with optimal combinations of cytokines and niche cells, such as endothelial cells (ECs), could augment the efficiency of hCB expansion. We have devised an approach to cultivate primary human ECs (hECs) in serum-free culture conditions. We demonstrate that coculture of CD34+ hCB in direct cellular contact with hECs and minimal concentrations of thrombopoietin/Kit-ligand/Flt3-ligand resulted in a 400-fold expansion of total hematopoietic cells, 150-fold expansion of CD45+CD34+ progenitor cells, and 23-fold expansion of CD45+ Lin−CD34hi+CD45RA−CD49f+ stem and progenitor cells over a 12-day period. Compared with cytokines alone, coculture of hCB with hECs permitted greater expansion of cells capable of multilineage engraftment and serial transplantation, hallmarks of long-term repopulating hematopoietic stem cells. Therefore, hECs establish a cellular platform for expansion of hematopoietic stem and progenitor cells and treatment of hematologic disorders.

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