Complexity of bone marrow hematopoietic stem cell niche

Asada, Noboru; Takeishi, Shoichiro; Frenette, Paul S.

doi:10.1007/s12185-017-2262-9

Cited by 118 publications

(102 citation statements)

References 60 publications

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“…The developed HSC niche model enables the culture of HSPCs in vitro, using primary human cells that form the main cellular components of the HSC niche . The model allows further study of interactions between various supportive cell types and HSPCs.…”

Section: Discussionmentioning

confidence: 99%

“…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 . Also endothelial cells have been shown to play a key role in the regulation of HSPCs, expressing high levels of major niche factors . Even though quiescent HSCs have been identified preferentially near the perivascular niche, this environment is not mimicked in previously developed in vitro HSC niche models.…”

Section: Discussionmentioning

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%

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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“…In murine BM, MSCs occupy specific anatomic positions defined as endosteal and vascular niche [5,45]. In particular, MSCs localize in the endosteal niche, lining the bone surface and physically interacting with both osteoblasts and HSPCs [6,46,47]. Endosteal MSCs represent a source of osteoprogenitors and indirectly contribute to osteogenesis by secreting several growth factors and cytokines [48].…”

Section: Mscs As Key Elements Of the Bone Marrow Nichementioning

confidence: 99%

Bone Marrow-Derived Mesenchymal Stromal Cells: A Novel Target to Optimize Hematopoietic Stem Cell Transplantation Protocols in Hematological Malignancies and Rare Genetic Disorders

Crippa

Santi

Bosotti

et al. 2019

JCM

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Mesenchymal stromal cells (MSCs) are crucial elements in the bone marrow (BM) niche where they provide physical support and secrete soluble factors to control and maintain hematopoietic stem progenitor cells (HSPCs). Given their role in the BM niche and HSPC support, MSCs have been employed in the clinical setting to expand ex-vivo HSPCs, as well as to facilitate HSPC engraftment in vivo. Specific alterations in the mesenchymal compartment have been described in hematological malignancies, as well as in rare genetic disorders, diseases that are amenable to allogeneic hematopoietic stem cell transplantation (HSCT), and ex-vivo HSPC-gene therapy (HSC-GT). Dissecting the in vivo function of human MSCs and studying their biological and functional properties in these diseases is a critical requirement to optimize transplantation outcomes. In this review, the role of MSCs in the orchestration of the BM niche will be revised, and alterations in the mesenchymal compartment in specific disorders will be discussed, focusing on the need to correct and restore a proper microenvironment to ameliorate transplantation procedures, and more in general disease outcomes.

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“…At steady-state cell-intrinsic transcription factors, as well as epigenetic regulators [36] in combination with nichemediated signals maintain HSCs at a quiescent state [37,38]. However, during conditions of infection, inflammatory signals rapidly drive HSCs out of quiescence and induce transient proliferation.…”

Section: The Role Of (Necro)inflammation In Demandadapted Hematopoiesismentioning

confidence: 99%

Necroinflammation emerges as a key regulator of hematopoiesis in health and disease

Jost

Höckendorf

2018

Cell Death Differ

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The hematopoietic system represents an organ system with an exceptional capacity for the production of mature blood cells from a small and mostly quiescent pool of hematopoietic stem cells (HSCs). This extraordinary capacity includes selfrenewal but also the propensity to rapidly respond to extrinsic needs, such as acute infections, severe inflammation, and wound healing. In recent years, it became clear that inflammatory signals such as cytokines, chemokine and danger signals from pathogens (PAMPs) or dying cells (DAMPs) impact on HSCs, shaping their proliferation status, lineage bias, and repopulating ability and subsequently increasing the output of mature effector cells. However, inflammatory danger signals negatively impact on the capacity of HSCs to self-renew and to maintain their stem cell capabilities. This is evidenced in conditions of chronic inflammation where bone marrow failure may originate from HSC exhaustion. Even in hematopoietic cancers, inflammatory signals shape the phenotype of the malignant clone as exemplified by necrosome-dependent inflammation elicited during malignant transformation in acute myeloid leukemia. Accordingly, understanding the contribution of inflammatory signals, and specifically necroinflammation, to HSC integrity, HSC long-term functionality, and malignant transformation has attracted substantial research and clinical interest. In this review, we highlight recent developments and open questions at the interplay between inflammation, regulated necrosis, and HSC biology in the context of blood cell development, acute and chronic inflammation, and hematopoietic cancer.

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Complexity of bone marrow hematopoietic stem cell niche

Cited by 118 publications

References 60 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

Bone Marrow-Derived Mesenchymal Stromal Cells: A Novel Target to Optimize Hematopoietic Stem Cell Transplantation Protocols in Hematological Malignancies and Rare Genetic Disorders

Necroinflammation emerges as a key regulator of hematopoiesis in health and disease

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