Ex vivo expansion of hematopoietic stem cells

Xie, Jingjing; Zhang, Chengcheng

doi:10.1007/s11427-015-4895-3

Cited by 20 publications

(12 citation statements)

References 197 publications

(255 reference statements)

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“…The detailed mechanistic pathway to reveal the exact genes or modifiers is remained to be elucidated, however, pan-inhibitors of DNA methylation are considered for preclinical and clinical application. The DNA methyltransferase inhibitors (DNMTI) including histone deacetylase (HDAC) inhibitors (valproic acid) [ 20 21 22 ], 5-aza-2'-deoxycytidine (AZA) [ 20 23 ], and nicotinamide (NAM, class3 HDAC-SIRT1 inhibitor) [ 8 20 24 ] are currently being tested for their efficacy in reducing hypermethylation of the regulatory or marker genes in hematopoiesis during ex vivo expansion. Also a large scale chemical library screening has been applied to increase long-term survival of cultured HSCs [ 20 ].…”

Section: Efforts For Ex Vivo Expansion Of Hscsmentioning

confidence: 99%

Hematopoietic stem cell expansion and generation: the ways to make a breakthrough

2015

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Hematopoietic stem cell transplantation (HSCT) is the first field where human stem cell therapy was successful. Flooding interest on human stem cell therapy to cure previously incurable diseases is largely indebted to HSCT success. Allogeneic HSCT has been an important modality to cure various diseases including hematologic malignancies, various non-malignant hematologic diseases, primary immunodeficiency diseases, and inborn errors of metabolism, while autologous HSCT is generally performed to rescue bone marrow aplasia following high-dose chemotherapy for solid tumors or multiple myeloma. Recently, HSCs are also spotlighted in the field of regenerative medicine for the amelioration of symptoms caused by neurodegenerative diseases, heart diseases, and others. Although the demand for HSCs has been growing, their supply often fails to meet the demand of the patients needing transplant due to a lack of histocompatible donors or a limited cell number. This review focuses on the generation and large-scale expansion of HSCs, which might overcome current limitations in the application of HSCs for clinical use. Furthermore, current proof of concept to replenish hematological homeostasis from non-hematological origin will be covered.

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Section: Efforts For Ex Vivo Expansion Of Hscsmentioning

confidence: 99%

Hematopoietic stem cell expansion and generation: the ways to make a breakthrough

2015

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“…Transplantation of cells into irradiated immunocompromised mice remains the gold standard assay for the assessment of the repopulation capability of hematopoietic stem cells. The successful repopulation of a vacant bone marrow niche proves that the cells are native HSCs (Jingjing and ChengCheng, 2015; Nakamura-Ishizu et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Bone marrow-on-a-chip: Emulating the human bone marrow

Sieber

Winter²,

et al. 2018

Preprint

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Multipotent hematopoietic stem and progenitor cells HSPC reside in specialized stem cell niches within the bone marrow, that provide a suitable microenvironment for lifelong maintenance of the stem cells. Meaningful in vitro models recapitulating the in vivo stem cell niche biology can be employed for both basic research as well as for applied sciences and represent a powerful tool to reduce animal tests in preclinical studies. Recently we published the generation of an in vitro bone marrow niche model, capable of long-term cultivation of HSC based on an organ-on-a-chip platform. This study provides a detailed analysis of the 3D culture system including matrix environment analysis by SEM, transcriptome analysis and system intrinsic differentiation induction. Furthermore, the bone marrow on a chip model can serve to multiply and harvest HSPC, since repeated cell removal not compromised the functionality of the culture system. The prolongation of the culture time to 8 weeks demonstrate the capacity to apply the model in repeated drug testing experiments. The quality of the presented system is emphasized by the differentiation capacity of long-term cultivated HSPC in vitro and in vivo. Transplanted human HSPC migrated actively into the bone marrow of irradiated mice and contributed to the long-term reconstitution of the hematopoietic system after four and eight weeks of in vitro cultivation.The introduced system offers a multitude of possible applications to address a broad spectrum of questions regarding HSPC, the corresponding bone marrow niche biology, and pathological aberrations.

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“…Co-culture of HSCs is one of the most frequently used models for understanding how the highly specific bone marrow niche interacts ex vivo with hematopoietic cells, promoting their differentiation and expansion. The technique can focus on the importance of non-contact culture systems on the successful maintenance of hematopoietic cells [47] and on the use of the stroma as a cell layer to provide support for HSC culturing, as mentioned above. Several studies have shown that contact between HSCs and stromal cells is important for maintaining HSC function [48,49].…”

Section: Stem Cell Culture Methodsmentioning

confidence: 99%

Traditional and Advanced Cell Cultures in Hematopoietic Stem Cell Studies

Ribeiro-Filho

Levy

Ruiz

et al. 2019

Cells

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Hematopoiesis is the main function of bone marrow. Human hematopoietic stem and progenitor cells reside in the bone marrow microenvironment, making it a hotspot for the development of hematopoietic diseases. Numerous alterations that correspond to disease progression have been identified in the bone marrow stem cell niche. Complex interactions between the bone marrow microenvironment and hematopoietic stem cells determine the balance between the proliferation, differentiation and homeostasis of the stem cell compartment. Changes in this tightly regulated network can provoke malignant transformation. However, our understanding of human hematopoiesis and the associated niche biology remains limited due to accessibility to human material and the limits of in vitro culture models. Traditional culture systems for human hematopoietic studies lack microenvironment niches, spatial marrow gradients, and dense cellularity, rendering them incapable of effectively translating marrow physiology ex vivo. This review will discuss the importance of 2D and 3D culture as a physiologically relevant system for understanding normal and abnormal hematopoiesis.

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Ex vivo expansion of hematopoietic stem cells

Cited by 20 publications

References 197 publications

Hematopoietic stem cell expansion and generation: the ways to make a breakthrough

Hematopoietic stem cell expansion and generation: the ways to make a breakthrough

Bone marrow-on-a-chip: Emulating the human bone marrow

Traditional and Advanced Cell Cultures in Hematopoietic Stem Cell Studies

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