Individual and combined effects of mesenchymal stromal cells and recombinant stimulatory cytokines on the in vitro growth of primitive hematopoietic cells from human umbilical cord blood

Flores-Guzmán, Patricia; Flores-Figueroa, Eugenia; Montesinos, Juan José; Martı́nez-Jaramillo, Guadalupe; Fernández-Sánchez, Verónica; Valencia-Plata, Ignacio; Alarcon-Santos, Guadalupe; Mayani, Héctor

doi:10.3109/14653240903180076

Cited by 31 publications

(18 citation statements)

References 34 publications

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“…Hematopoietic progenitor cells capable of forming colonies in vitro (colony-forming cells, CFC) were assayed in methylcellulose-based semisolid cultures (MethoCult, STI), as described [36, 37]. …”

Section: Methodsmentioning

confidence: 99%

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Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1

Purizaca

Contreras-Quiroz

Dorantes-Acosta

et al. 2013

Clinical and Developmental Immunology

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Acute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM) has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34+ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested.

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Section: Methodsmentioning

confidence: 99%

“…Cultures were sustained for 5 weeks, cells harvested, and proportions plated in semi-solid cultures for quantification of CFC [37]. …”

Section: Methodsmentioning

confidence: 99%

Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1

Purizaca

Contreras-Quiroz

Dorantes-Acosta

et al. 2013

Clinical and Developmental Immunology

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“…Importantly, MSC have been proposed as an adjuvant cellular therapy to promote hematopoietic recovery in patients subjected to HCT, particularly to avoid GvHD, and enhance cellular engraftment . In addition, MSC have long been used to support the ex vivo expansion of HSPC . Indeed, since the establishment of long‐term cultures of BM stromal cells to be used as hematopoietic supportive feeder layers in Dexter‐type cultures, MSC have been conventionally cultured as 2‐D adherent cells to tissue culture polystyrene (TCPS) and explored in HSPC co‐culture systems.…”

Section: The Hematopoietic Supportive Capacity Of the Native Niche Anmentioning

confidence: 99%

Hematopoietic Niche – Exploring Biomimetic Cues to Improve the Functionality of Hematopoietic Stem/Progenitor Cells

Costa

Soure

Cabral

et al. 2017

Biotechnology Journal

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The adult bone marrow (BM) niche is a complex entity where a homeostatic hematopoietic system is maintained through a dynamic crosstalk between different cellular and non-cellular players. Signaling mechanisms triggered by cell-cell, cell-extracellular matrix (ECM), cell-cytokine interactions, and local microenvironment parameters are involved in controlling quiescence, self-renewal, differentiation, and migration of hematopoietic stem/progenitor cells (HSPC). A promising strategy to more efficiently expand HSPC numbers and tune their properties ex vivo is to mimic the hematopoietic niche through integration of adjuvant stromal cells, soluble cues, and/or biomaterial-based approaches in HSPC culture systems. Particularly, mesenchymal stem/stromal cells (MSC), through their paracrine activity or direct contact with HSPC, are thought to be a relevant niche player, positioning HSPC-MSC co-culture as a valuable platform to support the ex vivo expansion of hematopoietic progenitors. To improve the clinical outcome of hematopoietic cell transplantation (HCT), namely when the available HSPC are present in a limited number such is the case of HSPC collected from umbilical cord blood (UCB), ex vivo expansion of HSPC is required without eliminating the long-term repopulating capacity of more primitive HSC. Here, we will focus on depicting the characteristics of co-culture systems, as well as other bioengineering approaches to improve the functionality of HSPC ex vivo.

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“…These combinations usually include early acting cytokines, such as stem cell factor (SCF), the ligand for FLT-3 (FLT3-L), and thrombopoietin (TPO). Interestingly, other elements, such as mesenchymal stromal cells, metal chelators, Notch ligands, or small molecules that favor stem cell self-renewal (such as UM171, OAC1, SR1, nicotinamide, and Resveratrol), have also been incorporated into some of these systems [23][24][25][26][27][28]. In fact, some of these molecules have already been tested in clinical settings or are close to being tested.…”

Section: Introductionmentioning

confidence: 99%

Functional Integrity and Gene Expression Profiles of Human Cord Blood-Derived Hematopoietic Stem and Progenitor Cells Generated In Vitro

Dircio-Maldonado¹,

Flores-Guzmán²,

Corral-Navarro³

et al. 2018

Stem Cells Translational Medicine

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To date, different experimental strategies have been developed for the ex vivo expansion of human hematopoietic stem (HSCs) and progenitor (HPCs) cells. This has resulted in significant advances on the use of such expanded cells in transplantation settings. To this day, however, it is still unclear to what extent those stem and progenitor cells generated in vitro retain the functional and genomic integrity of their freshly isolated counterparts. In trying to contribute to the solving of this issue, in the present study we have selected and purified three different hematopoietic cell populations: HSCs (CD34+ CD38‐ CD45RA‐ CD71‐ Lin‐ cells), myeloid progenitor cells (CD34+ CD38+ CD45RA+ CD71‐ Lin‐ cells), and erythroid progenitor cells (CD34+ CD38+ CD45RA‐ CD71+ Lin‐ cells), obtained directly from fresh human umbilical cord blood (UCB) units or generated in vitro under particular culture conditions. We, then, compared their functional integrity in vitro and their gene expression profiles. Our results indicate that in spite of being immunophenotipically similar, fresh and in vitro generated cells showed significant differences, both in functional and genetic terms. As compared to their fresh counterparts, those HSCs generated in our culture system showed a deficient content of long‐term culture‐initiating cells, and a marked differentiation bias toward the myeloid lineage. In addition, in vitro generated HSCs and HPCs showed a limited expansion potential. Such functional alterations correlated with differences in their gene expression profiles. These observations are relevant in terms of HSC biology and may have implications in UCB expansion and transplantation. Stem Cells Translational Medicine 2018;7:602–614

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Individual and combined effects of mesenchymal stromal cells and recombinant stimulatory cytokines on the in vitro growth of primitive hematopoietic cells from human umbilical cord blood

Cited by 31 publications

References 34 publications

Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1

Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1

Hematopoietic Niche – Exploring Biomimetic Cues to Improve the Functionality of Hematopoietic Stem/Progenitor Cells

Functional Integrity and Gene Expression Profiles of Human Cord Blood-Derived Hematopoietic Stem and Progenitor Cells Generated In Vitro

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