Redistribution, homing and organ-invasion of neoplastic stem cells in myeloid neoplasms

Valent, Peter; Sadovnik, Irina; Eisenwort, Gregor; Herrmann, Harald; Bauer, Karin; Mueller, Niklas; Sperr, Wolfgang R.; Wicklein, Daniel; Schumacher, Udo

doi:10.1016/j.semcancer.2019.07.025

Cited by 16 publications

(8 citation statements)

References 170 publications

(337 reference statements)

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“…The same processes which affect normal HSPC homing can also affect leukemia stem cell migration and homing to extramedullary tissue niches or their return to marrow where they can pirate the normal hematopoietic niche 52 . These leukemia initiating cells often circulate along with leukemia blasts.…”

Section: Hspc Homing: Rolling Adhesion and Transmigrationmentioning

confidence: 99%

Stem cell homing: From physiology to therapeutics

2020

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Stem cell homing is a multistep endogenous physiologic process that is also used by exogenously administered hematopoietic stem and progenitor cells (HSPCs). This multistep process involves cell migration and is essential for hematopoietic stem cell transplantation. The process can be manipulated to enhance ultimate engraftment potential, and understanding stem cell homing is also important to the understanding of stem cell mobilization. Homing is also of potential importance in the recruitment of marrow mesenchymal stem and stromal cells (MSCs) to sites of injury and regeneration. This process is less understood but assumes importance when these cells are used for repair purposes. In this review, the process of HSPC and MSC homing is examined, as are methods to enhance this process.

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Section: Hspc Homing: Rolling Adhesion and Transmigrationmentioning

confidence: 99%

Stem cell homing: From physiology to therapeutics

2020

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“…The high expression of CXCR4 on CD34 + leukemic blasts suggest that their migration capacity is also regulated over the CXCL12-CXCR4 axis. This hypothesis is supported by the evidence that the CXCL12-CXCR4 signaling pathway is crucial for leukemic blast survival as well as for in vivo homing and repopulation of the healthy hematopoietic niche 55,56 . It is known that the vascular density is increased in the AML marrow, while the role of the sinusoidal endothelium on leukemic blasts is still not understood.…”

Section: Discussionmentioning

confidence: 83%

Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

Giger

Hofer

Miljkovic‐Licina

et al. 2021

Preprint

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In many leukemia patients, a poor prognosis is attributed either to the development of chemotherapy resistance by leukemic stem cells (LSCs) or to the inefficient engraftment of transplanted hematopoietic stem/progenitor cells (HSPCs) into the bone marrow (BM). Here, we build a 3D in vitro model system of bone marrow organoids (BMOs) that recapitulate several structural and cellular components of native BM. These organoids are formed in a high-throughput manner from the aggregation of endothelial and mesenchymal cells within hydrogel microwells. Accordingly, the mesenchymal compartment shows partial maintenance of its self-renewal and multilineage potential, while endothelial cells self-organize into an interconnected vessel-like network. Intriguingly, such a vascular compartment enhances the recruitment of HSPCs in a chemokine ligand/receptor-dependent manner, reminiscent of HSPC homing behavior in vivo. Additionally, we also model LSC migration and nesting in BMOs, thus highlighting the potential of this system as a well accessible and scalable preclinical model for candidate drug screening and patient-specific assays.

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“…This hypothesis is supported by the evidence that the CXCL12–CXCR4 signaling pathway is crucial for leukemic blast survival as well as for in vivo homing and repopulation of the healthy hematopoietic niche. 55,56 It is known that the vascular density is increased in the AML marrow, while the role of the sinusoidal endothelium on leukemic blasts is still not understood. Thus, our BMOs, which contain a complex endothelial-like network, provide an in vitro environment to investigate and understand such endothelial–leukemia cell interactions in future studies.…”

Section: Discussionmentioning

confidence: 99%

Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

et al. 2022

View full text Add to dashboard Cite

In many leukemia patients, a poor prognosis is attributed either to the development of chemotherapy resistance by leukemic stem cells (LSCs) or to the inefficient engraftment of transplanted hematopoietic stem/progenitor cells (HSPCs) into the bone marrow (BM). Here, we build a 3D in vitro model system of bone marrow organoids (BMOs) that recapitulate several structural and cellular components of native BM. These organoids are formed in a high-throughput manner from the aggregation of endothelial and mesenchymal cells within hydrogel microwells. Accordingly, the mesenchymal compartment shows partial maintenance of its self-renewal and multilineage potential, while endothelial cells self-organize into an interconnected vessel-like network. Intriguingly, such an endothelial compartment enhances the recruitment of HSPCs in a chemokine ligand/receptor-dependent manner, reminiscent of HSPC homing behavior in vivo. Additionally, we also model LSC migration and nesting in BMOs, thus highlighting the potential of this system as a well accessible and scalable preclinical model for candidate drug screening and patient-specific assays.

show abstract

Redistribution, homing and organ-invasion of neoplastic stem cells in myeloid neoplasms

Cited by 16 publications

References 170 publications

Stem cell homing: From physiology to therapeutics

Stem cell homing: From physiology to therapeutics

Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

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