From the niche to malignant hematopoiesis and back: reciprocal interactions between leukemia and the bone marrow microenvironment

Soto, Celia; Celso, Cristina Lo; Purton, Louise E.; Frisch, B.

doi:10.1002/jbm4.10516

Cited by 11 publications

(14 citation statements)

References 128 publications

(236 reference statements)

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“…In particular, our group and others have shown that leukemic cell interaction with osteoblasts is an important component in sustaining leukemic burden. However, the interactions of the HSC niche with bone marrow pathologies are poorly understood ( Soto et al, 2021 ). AML is the most common form of leukemia that arises in the bone marrow ( Soto et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, the interactions of the HSC niche with bone marrow pathologies are poorly understood ( Soto et al, 2021 ). AML is the most common form of leukemia that arises in the bone marrow ( Soto et al, 2021 ). The standard therapy for AML of combined daunorubicin and cytarabine administration, termed 7 + 3 induction therapy, which was first employed in the 1970s, is still the predominant upfront therapy for most AML patients and gives rise to poor outcomes with an overall 5-years survival rate of <30% ( Roussel et al, 2020 ; Kantarjian et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, osteocytes embedded in bone are the most abundant bone cell in vivo and are not present in our BMME-on-chip ( Frisch, 2019 ). The relative importance of these cells and processes for the regulation of HSCs are not well-established, and thus the implication of their absence in our system is not known ( Soto et al, 2021 ). However, the ability of our BMME-on-chip to maintain a fully functional HSC population suggests that they are not required for HSC maintenance.…”

Section: Limitationsmentioning

confidence: 99%

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Bone Marrow Microenvironment-On-Chip for Culture of Functional Hematopoietic Stem Cells

Sharipol

Lesch²,

Soto³

et al. 2022

Front. Bioeng. Biotechnol.

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Hematopoiesis takes place in the bone marrow and is supported by a complex cellular and molecular network in the bone marrow microenvironment. Commonly used models of the human bone marrow microenvironment include murine models and two-dimensional and three-dimensional tissue cultures. While these model systems have led to critical advances in the field, they fail to recapitulate many aspects of the human bone marrow. This has limited our understanding of human bone marrow pathophysiology and has led to deficiencies in therapy for many bone marrow pathologies such as bone marrow failure syndromes and leukemias. Therefore, we have developed a modular murine bone marrow microenvironment-on-chip using a commercially available microfluidic platform. This model includes a vascular channel separated from the bone marrow channel by a semi-porous membrane and incorporates critical components of the bone marrow microenvironment, including osteoblasts, endothelial cells, mesenchymal stem cells, and hematopoietic stem and progenitor cells. This system is capable of maintaining functional hematopoietic stem cells in vitro for at least 14 days at frequencies similar to what is found in the primary bone marrow. The modular nature of this system and its accessibility will allow for acceleration of our understanding of the bone marrow.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Limitationsmentioning

confidence: 99%

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Bone Marrow Microenvironment-On-Chip for Culture of Functional Hematopoietic Stem Cells

Sharipol

Lesch²,

Soto³

et al. 2022

Front. Bioeng. Biotechnol.

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“…Growth and survival of the malignant clone is favoured by age-related or inflammationdriven changes in the BM microenvironment (BMME) (43,44). On the other hand, BMME is affected by signals coming from mutated HSCs, in a bidirectional crosstalk (45).…”

Section: Composition Of Bm Nichesmentioning

confidence: 99%

Bone Marrow Niches and Tumour Cells: Lights and Shadows of a Mutual Relationship

et al. 2022

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The bone marrow (BM) niche is the spatial structure within the intra-trabecular spaces of spongious bones and of the cavity of long bones where adult haematopoietic stem cells (HSCs) maintain their undifferentiated and cellular self-renewal state through the intervention of vascular and nervous networks, metabolic pathways, transcriptional and epigenetic regulators, and humoral signals. Within the niche, HSCs interact with various cell types such as osteoblasts, endothelial cells, macrophages, and mesenchymal stromal cells (MSCs), which maintain HSCs in a quiescent state or sustain their proliferation, differentiation, and trafficking, depending on body needs. In physiological conditions, the BM niche permits the daily production of all the blood and immune cells and their admittance/ingress/progression into the bloodstream. However, disruption of this delicate microenvironment promotes the initiation and progression of malignancies such as those included in the spectrum of myeloid neoplasms, also favouring resistance to pharmacological therapies. Alterations in the MSC population and in the crosstalk with HSCs owing to tumour-derived factors contribute to the formation of a malignant niche. On the other hand, cells of the BM microenvironment cooperate in creating a unique milieu favouring metastasization of distant tumours into the bone. In this framework, the pro-tumorigenic role of MSCs is well-documented, and few evidence suggest also an anti-tumorigenic effect. Here we will review recent advances regarding the BM niche composition and functionality in normal and in malignant conditions, as well as the therapeutic implications of the interplay between its diverse cellular components and malignant cells.

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“…To understand LSCs survival mechanisms, it is crucial to understand how leukemia cells interact with different elements of the 3D bone marrow microenvironment [ 11 ]. Such need has fueled the interest in developing 3D in vitro AML culture models in the last decade.…”

Section: Introductionmentioning

confidence: 99%

The Potential Role of 3D In Vitro Acute Myeloid Leukemia Culture Models in Understanding Drug Resistance in Leukemia Stem Cells

Al-Kaabneh

Frisch

Aljitawi

2022

Cancers

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The complexity of the bone marrow (BM) microenvironment makes studying hematological malignancies in vitro a challenging task. Three-dimensional cell cultures are being actively studied, particularly due to their ability to serve as a bridge of the gap between 2D cultures and animal models. The role of 3D in vitro models in studying the mechanisms of chemotherapeutic resistance and leukemia stem cells (LSCs) in acute myeloid leukemia (AML) is not well-reviewed. We present an overview of 3D cell models used for studying AML, emphasizing the recent advancements in microenvironment modeling, chemotherapy testing, and resistance.

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From the niche to malignant hematopoiesis and back: reciprocal interactions between leukemia and the bone marrow microenvironment

Cited by 11 publications

References 128 publications

Bone Marrow Microenvironment-On-Chip for Culture of Functional Hematopoietic Stem Cells

Bone Marrow Microenvironment-On-Chip for Culture of Functional Hematopoietic Stem Cells

Bone Marrow Niches and Tumour Cells: Lights and Shadows of a Mutual Relationship

The Potential Role of 3D In Vitro Acute Myeloid Leukemia Culture Models in Understanding Drug Resistance in Leukemia Stem Cells

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