Traditional and Advanced Cell Cultures in Hematopoietic Stem Cell Studies

Antonio Carlos Ribeiro-Filho, Débora Levy, Jorge Luis Maria Ruiz, Marluce da Cunha Mantovani, Sérgio Paulo Bydlowski, Antonio Carlos Ribeiro-Filho, Débora Levy, Jorge Luis Maria Ruiz, Marluce da Cunha Mantovani, Sérgio Paulo Bydlowski

Abstract

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.

Keywords: 2D culture; 3D culture; hematopoiesis; hematopoietic stem cells; stem cell culture.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Hierarchy of human hematopoiesis. LT-HSC: Long Term-Hematopoietic Stem Cell; ST-HSC: Short Term-Hematopoietic Stem Cell; MPP: Multipotent Progenitor; OPP: Oligopotent Progenitor; LRP: Lineage Restricted Progenitor; MEC: Mature Effector Cell. The markers of the most important lineages are listed: Common Lymphoid Progenitor (CLP); Common Myeloid Progenitor (CMP); Megakaryocyte-Erythrocyte Progenitor (MEP); Granulocyte-Macrophage Progenitor (GMP). Restricted lineage progenitor cells: Megakaryocyte Progenitor (MkP); Erythrocytic Progenitor (EryP); Granulocytic Progenitor (GrP); Monocyte Progenitor (MncP); Dendritic Progenitor Cell (Pro DC); Progenitor Cell-T (Pro-T); Progenitor Cell-B (Pro-B); Progenitor Cell-Nk (Pro-Nk).
Figure 2
Figure 2
Two-dimensional (2D) and three-dimensional (3D) cell culture. (A) Schematic model of 2D cell culture. Standard model of 2D cell culture. Cells are cultured as a single layer in a culture flask. (B) Schematic model of 3D cell culture. 3D model of cell culture giving the notion of height, width and depth; cells are surrounded by the medium. (C) Example of 2D culture. HEK 293 cells in 2D cell culture; the adherence to a flat surface provides mechanical support for growth in monolayers. Scale bar 400 μm. (D) Example of 3D culture. HEK 293 cells 3D cell culture in agarose allowing the cells to grow or interact with their surroundings in all three dimensions. Scale bar 1000 μm.

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