Bone Marrow Homing and Engraftment Defects of Human Hematopoietic Stem and Progenitor Cells

Caocci, Giovanni; Nasa, Giorgio La

doi:10.4084/mjhid.2017.032

Cited by 30 publications

(26 citation statements)

References 72 publications

(72 reference statements)

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“…Successful bone marrow engraftment requires HSPC homing to the bone marrow vasculature, trans-endothelial migration, and lodging to the bone marrow niche. Research over the past few decades has revealed proteins that play key roles in HSPC homing and engraftment including selectins, ICAM-1, VCAM-1 on the EC 53,54 , beta1 subfamily integrins, and CXCR4 on HSPCs 2,55,56 . However, the mechanisms involved in trans-endothelial migration of HSPCs were unclear since loss of function studies focusing on these proteins showed HSPC defects mainly in short-term homing or long-term engraftment processes.…”

Section: Discussionmentioning

confidence: 99%

Diaphanous-related formin mDia2 regulates beta2 integrins to control hematopoietic stem and progenitor cell engraftment

et al. 2020

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Bone marrow engraftment of the hematopoietic stem and progenitor cells (HSPCs) involves homing to the vasculatures and lodgment to their niches. How HSPCs transmigrate from the vasculature to the niches is unclear. Here, we show that loss of diaphanous-related formin mDia2 leads to impaired engraftment of long-term hematopoietic stem cells and loss of competitive HSPC repopulation. These defects are likely due to the compromised transendothelial migration of HSPCs since their homing to the bone marrow vasculatures remained intact. Mechanistically, loss of mDia2 disrupts HSPC polarization and induced cytoplasmic accumulation of MAL, which deregulates the activity of serum response factor (SRF). We further reveal that beta2 integrins are transcriptional targets of SRF. Knockout of beta2 integrins in HSPCs phenocopies mDia2 deficient mice. Overexpression of SRF or beta2 integrins rescues HSPC engraftment defects associated with mDia2 deficiency. Our findings show that mDia2-SRF-beta2 integrin signaling is critical for HSPC lodgment to the niches.

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Section: Discussionmentioning

confidence: 99%

Diaphanous-related formin mDia2 regulates beta2 integrins to control hematopoietic stem and progenitor cell engraftment

et al. 2020

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“…Mesenchymal stem cells alone have been proposed to have beneficial effects in patients suffering a multitude of pathologies across body systems, including: the lungs, brain, musculoskeletal system, peripheral nervous system, skin, and the heart . Although some have reported that direct injection of these cells into the affected tissues can have beneficial therapeutic effects, the level of engraftment of the cells to the site of application typically ranges between only 1% and 10%, and has been proposed to be as low as 0.001% . As a result, the number of cells that are typically used in these therapies tend to be very large, ultimately creating the potential for carcinogenesis and other negative outcomes.…”

Section: The Delivery Of Biological Therapeutics Using Hydrogelsmentioning

confidence: 99%

Structuring of Hydrogels across Multiple Length Scales for Biomedical Applications

et al. 2018

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The development of new materials for clinical use is limited by an onerous regulatory framework, which means that taking a completely new material into the clinic can make translation economically unfeasible. One way to get around this issue is to structure materials that are already approved by the regulator, such that they exhibit very distinct physical properties and can be used in a broader range of clinical applications. Here, the focus is on the structuring of soft materials at multiple length scales by modifying processing conditions. By applying shear to newly forming materials, it is possible to trigger molecular reorganization of polymer chains, such that they aggregate to form particles and ribbon-like structures. These structures then weakly interact at zero shear forming a solid-like material. The resulting self-healing network is of particular use for a range of different biomedical applications. How these materials are used to allow the delivery of therapeutic entities (cells and proteins) and as a support for additive layer manufacturing of larger-scale tissue constructs is discussed. This technology enables the development of a range of novel materials and structures for tissue augmentation and regeneration.

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“…A first step in this process is homing of infused intravenously HSPCs to BM followed by their lodging into hematopoietic niches and engraftment. The homing process is facilitated by chemoattractants secreted from BM in response to myeloablative conditioning [4][5][6]. A crucial role in this step plays an α-chemokine stromal derived factor-1 (SDF-1) secreted by BM cells that survived myeloablative treatment [5,7,8].…”

Section: Introductionmentioning

confidence: 99%

A Novel Evidence That Mannan Binding Lectin (MBL) Pathway of Complement Cascade Activation is Involved in Homing and Engraftment of Hematopoietic Stem Progenitor Cells (HSPCs)

Adamiak

Cymer

Anusz

et al. 2020

Stem Cell Rev and Rep

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Delayed homing and engraftment of hematopoietic stem progenitor cells (HSPCs) or even failure to engraft at all is significant clinical problem after hematopoietic transplant. Therefore, in order to develop more efficient homing and engraftment facilitating strategies it is important to learn more about this process. Our team has postulated that myeloablative conditioning for transplantation induces in bone marrow (BM) microenvironment a state of sterile inflammation in which elements of innate immunity activated by radio-or chemotherapy conditioning for transplant play an important role. In frame with this claim we reported that a significant role in this process plays activation of complement cascade (ComC). Accordingly, mice that that lack a fifth component (C5) of ComC turned out to engraft poorly with normal syngeneic BM cells as compared to normal control animals. In extension of our previous studies we provide for first time evidence that mannan binding lectin (MBL) pathway is involved in activation of ComC in myeloablated transplant recipient BM and thus plays an important role in homing and engraftment of HSPCs. To support this MBL-KO mice show significant defect in hematopoietic reconstitution after hematopoietic transplantation. This correlates with a decrease in expression of stromal derived factor-1 (SDF-1) and impaired activation of Nlrp3 inflammasome in irradiated BM of these mice.

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Bone Marrow Homing and Engraftment Defects of Human Hematopoietic Stem and Progenitor Cells

Cited by 30 publications

References 72 publications

Diaphanous-related formin mDia2 regulates beta2 integrins to control hematopoietic stem and progenitor cell engraftment

Diaphanous-related formin mDia2 regulates beta2 integrins to control hematopoietic stem and progenitor cell engraftment

Structuring of Hydrogels across Multiple Length Scales for Biomedical Applications

A Novel Evidence That Mannan Binding Lectin (MBL) Pathway of Complement Cascade Activation is Involved in Homing and Engraftment of Hematopoietic Stem Progenitor Cells (HSPCs)

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