3D models of the hematopoietic stem cell niche under steady-state and active conditions

Rödling, Lisa; Schwedhelm, Ivo; Kraus, Saskia; Bieback, Karen; Hansmann, Jan; Lee-Thedieck, Cornelia

doi:10.1038/s41598-017-04808-0

Cited by 69 publications

(70 citation statements)

References 104 publications

(82 reference statements)

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“…The model allows further study of interactions between various supportive cell types and HSPCs. Current 3D models are based on MSCs and/or O‐MSCs, mimicking only the endosteal niche . MSCs as well as adipogenic and osteogenic progenitors are known to be an essential component of the HSC niche, required for the quiescence, proliferation, and differentiation of HSPCs .…”

Section: Discussionmentioning

confidence: 99%

“…Also cytokine supplemented media was used, with less supportive capacities toward primitive HSPCs over time when compared to feeder cell lines . Other studies focused on optimizing hydrogels or culture conditions did not include controls containing supportive cells or cytokines other than the ones tested in their endosteal models . A direct comparison of culture conditions and components required for the maintenance of HSPC is preferred, in order to evaluate the supportive potential of experimental conditions in newly developed in vitro HSC niche models.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to these materials, models used either stromal cell lines or human primary cells as supportive cell sources. The primary cell sources are multipotent mesenchymal stromal cells (MSCs) or osteogenic differentiated MSCs (O‐MSCs) . In these primary cell models, the use of additional cytokine supplemented medium is still common practice, to enhance the survival of the cultured HSPCs.…”

Section: Introductionmentioning

confidence: 99%

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A Human Hematopoietic Niche Model Supporting Hematopoietic Stem and Progenitor Cells In Vitro

Braham

Yim

Mateos

et al. 2019

Adv Healthcare Materials

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Niches in the bone marrow regulate hematopoietic stem and progenitor cell (HSPC) fate and behavior through cell–cell interactions and soluble factor secretion. The niche‐HSPC crosstalk is a very complex process not completely elucidated yet. To aid further investigation of this crosstalk, a functional in vitro 3D model that closely represents the main supportive compartments of the bone marrow is developed. Different combinations of human stromal cells and hydrogels are tested for their potential to maintain CD34+ HSPCs. Cell viability, clonogenic hematopoietic potential, and surface marker expression are assessed over time. Optimal HSPC support is obtained in presence of adipogenic and osteogenic cells, together with progenitor derived endothelial cells. When cultured in a bioactive hydrogel, the supportive cells self‐assemble into a hypoxic stromal network, stimulating CD34+CD38+ cell formation, while maintaining the pool of CD34+38− HSPCs. HSPC clusters colocalize with the stromal networks, in close proximity to sinusoidal clusters of CD31+ endothelial cells. Importantly, the primary in vitro niche model supports HSPCs with no cytokine addition. Overall, the engineered primary 3D bone marrow environment provides an easy and reliable model to further investigate interactions between HSPCs and their endosteal and perivascular niches, in the context of normal hematopoiesis or blood‐related diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Human Hematopoietic Niche Model Supporting Hematopoietic Stem and Progenitor Cells In Vitro

Braham

Yim

Mateos

et al. 2019

Adv Healthcare Materials

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“…Indeed, co‐culture of UCB hematopoietic cells with alginate microencapsulated MSC in a rotating wall vessel rendered higher expansion levels of total nucleated and CD34 + cells than static co‐culture or bioreactor culture alone while maintaining more primitive HSPC . On the other hand, Rodling and colleagues explored HSPC and MSC‐seeded PEG hydrogels on a perfused model of the BM niche and suggested that a similar approach could be followed in drug screening and toxicity testing . Microfluidic systems can also contribute to develop more efficient drugs, with higher specificity for treatment of hemato‐oncological diseases.…”

Section: Biomaterial‐supported Cultures Of Hspc In Bioreactorsmentioning

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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“…One of the main purposes of developing artificial bone marrow like structures for culturing leukaemia cells is drug sensitivities [27]. Foam-based 3D culture similar to fiber scaffolds [16] increased the resistance of the leukaemia cell lines to inhibitory effects of imatinib and to the maintenance of AML cells [29,30] and also selects bortezomib-resistant CML stem cells [31].…”

Section: Discussionmentioning

confidence: 99%

Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells

Karimpoor

Yebra-Fernandez

Parhizkar

et al. 2018

J. R. Soc. Interface.

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The development of assays for evaluating the sensitivity of leukaemia cells to anti-cancer agents is becoming an important aspect of personalized medicine. Conventional cell cultures lack the three-dimensional (3D) structure of the bone marrow (BM), the extracellular matrix and stromal components which are crucial for the growth and survival of leukaemia stem cells. To accurately predict the sensitivity of the leukaemia cells in an in vitro assay a culturing system containing the essential components of BM is required. In this study, we developed a porous calcium alginate foam-based scaffold to be used for 3D culture. The new 3D culture was shown to be cell compatible as it supported the proliferation of both normal haematopoietic and leukaemia cells. Our cell differential assay for myeloid markers showed that the porous foam-based 3D culture enhanced myeloid differentiation in both leukaemia and normal haematopoietic cells compared to two-dimensional culture. The foam-based scaffold reduced the sensitivity of the leukaemia cells to the tested antileukaemia agents in K562 and HL60 leukaemia cell line model and also primary myeloid leukaemia cells. This observation supports the application of calcium alginate foams as scaffold components of the 3D cultures for investigation of sensitivity to antileukaemia agents in primary myeloid cells.

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3D models of the hematopoietic stem cell niche under steady-state and active conditions

Cited by 69 publications

References 104 publications

A Human Hematopoietic Niche Model Supporting Hematopoietic Stem and Progenitor Cells In Vitro

A Human Hematopoietic Niche Model Supporting Hematopoietic Stem and Progenitor Cells In Vitro

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

Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells

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