Biomechanical cues as master regulators of hematopoietic stem cell fate

Li, Honghu; Luo, Qian; Shan, Wei; Cai, Shuyang; Tie, Ruxiu; Xu, Yan; Lin, Yaw Huei; Qian, Pengxu; Huang, He

doi:10.1007/s00018-021-03882-y

Cited by 23 publications

(21 citation statements)

References 229 publications

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“…Mechanical signals act as important influences on the fate of living organisms in a number of areas, including the circulatory system [ 143 ], neural tissue [ 144 ], tendon tissue engineering [ 145 ], periodontal tissue engineering [ 146 ], cartilage tissue engineering [ 15 ], and others. The effects of several mechanical forces on disease are specified below.…”

Section: Clinical Applications Of the Mechanical Environment Of Stem ...mentioning

confidence: 99%

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

Zhang

Wang

2022

Stem Cell Res Ther

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Stem cell differentiation is of great interest in medical research; however, specifically and effectively regulating stem cell differentiation is still a challenge. In addition to chemical factors, physical signals are an important component of the stem cell ecotone. The mechanical microenvironment of stem cells has a huge role in stem cell differentiation. Herein, we describe the knowledge accumulated to date on the mechanical environment in which stem cells exist, which consists of various factors, including the extracellular matrix and topology, substrate stiffness, shear stress, hydrostatic pressure, tension, and microgravity. We then detail the currently known signalling pathways that stem cells use to perceive the mechanical environment, including those involving nuclear factor-kB, the nicotinic acetylcholine receptor, the piezoelectric mechanosensitive ion channel, and hypoxia-inducible factor 1α. Using this information in clinical settings to treat diseases is the goal of this research, and we describe the progress that has been made. In this review, we examined the effects of mechanical factors in the stem cell growth microenvironment on stem cell differentiation, how mechanical signals are transmitted to and function within the cell, and the influence of mechanical factors on the use of stem cells in clinical applications.

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Section: Clinical Applications Of the Mechanical Environment Of Stem ...mentioning

confidence: 99%

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

Zhang

Wang

2022

Stem Cell Res Ther

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“…Hematopoietic stem cells are able to perceive both soluble signals and biomechanical inputs, including fluid mechanical stresses, from their microenvironment and are emerging as critical mechano-regulators of hematopoiesis. 151 The beating of the heart subjects HSCs to constant hemodynamic forces. In mice, circulating HSCs can experience shear stress that exceeds 600 dyn per cm 2 in regions of the aortic walls.…”

Section: Microgravitymentioning

confidence: 99%

“…Recently, it was shown that YAP activation and the upregulation of YAP target genes are sensitive to cyclic stretch, and for the first time, a connection between biomechanical cues and YAP in determining HSC fate has been confirmed. 167 Kruppel-like factor 2, 168 basic leucine zipper, 151 and cAMP response element-binding protein 169 may all also serve as other crucial transcription factors whose expression reflects the onset of fluid shear forces and prompts HSC differentiation.…”

Section: Microgravitymentioning

confidence: 99%

Changes in interstitial fluid flow, mass transport and the bone cell response in microgravity and normogravity

et al. 2022

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In recent years, our scientific interest in spaceflight has grown exponentially and resulted in a thriving area of research, with hundreds of astronauts spending months of their time in space. A recent shift toward pursuing territories farther afield, aiming at near-Earth asteroids, the Moon, and Mars combined with the anticipated availability of commercial flights to space in the near future, warrants continued understanding of the human physiological processes and response mechanisms when in this extreme environment. Acute skeletal loss, more severe than any bone loss seen on Earth, has significant implications for deep space exploration, and it remains elusive as to why there is such a magnitude of difference between bone loss on Earth and loss in microgravity. The removal of gravity eliminates a critical primary mechano-stimulus, and when combined with exposure to both galactic and solar cosmic radiation, healthy human tissue function can be negatively affected. An additional effect found in microgravity, and one with limited insight, involves changes in dynamic fluid flow. Fluids provide the most fundamental way to transport chemical and biochemical elements within our bodies and apply an essential mechano-stimulus to cells. Furthermore, the cell cytoplasm is not a simple liquid, and fluid transport phenomena together with viscoelastic deformation of the cytoskeleton play key roles in cell function. In microgravity, flow behavior changes drastically, and the impact on cells within the porous system of bone and the influence of an expanding level of adiposity are not well understood. This review explores the role of interstitial fluid motion and solute transport in porous bone under two different conditions: normogravity and microgravity.

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“…Fluid shear stress is absent in static culture systems despite this parameter can affect the hematopoietic niche through paracrine signaling stimulation, e.g. through Yap-1, Piezo 1 ( Heck et al, 2020 ; Zhou et al, 2020 ; Li et al, 2021 ). Endothelial cells can convert FSS into a biochemical response for the neighboring cells, regulating cycling and quiescence of HSCs ( Roux et al, 2020 ).…”

Section: Biophysical Factorsmentioning

confidence: 99%

Functionalized 3D scaffolds for engineering the hematopoietic niche

Bruschi

Vanzolini

Sahu

et al. 2022

Front. Bioeng. Biotechnol.

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Hematopoietic stem cells (HSCs) reside in a subzone of the bone marrow (BM) defined as the hematopoietic niche where, via the interplay of differentiation and self-renewal, they can give rise to immune and blood cells. Artificial hematopoietic niches were firstly developed in 2D in vitro cultures but the limited expansion potential and stemness maintenance induced the optimization of these systems to avoid the total loss of the natural tissue complexity. The next steps were adopted by engineering different materials such as hydrogels, fibrous structures with natural or synthetic polymers, ceramics, etc. to produce a 3D substrate better resembling that of BM. Cytokines, soluble factors, adhesion molecules, extracellular matrix (ECM) components, and the secretome of other niche-resident cells play a fundamental role in controlling and regulating HSC commitment. To provide biochemical cues, co-cultures, and feeder-layers, as well as natural or synthetic molecules were utilized. This review gathers key elements employed for the functionalization of a 3D scaffold that demonstrated to promote HSC growth and differentiation ranging from 1) biophysical cues, i.e., material, topography, stiffness, oxygen tension, and fluid shear stress to 2) biochemical hints favored by the presence of ECM elements, feeder cell layers, and redox scavengers. Particular focus is given to the 3D systems to recreate megakaryocyte products, to be applied for blood cell production, whereas HSC clinical application in such 3D constructs was limited so far to BM diseases testing.

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Biomechanical cues as master regulators of hematopoietic stem cell fate

Cited by 23 publications

References 229 publications

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

Changes in interstitial fluid flow, mass transport and the bone cell response in microgravity and normogravity

Functionalized 3D scaffolds for engineering the hematopoietic niche

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