Extravascular coagulation in hematopoietic stem and progenitor cell regulation

Nguyen, Thien S.; Lapidot, Tsvee; Ruf, Wolfram

doi:10.1182/blood-2017-12-768986

Cited by 39 publications

(31 citation statements)

References 103 publications

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“…Moreover, the DAMPs Hmgb1 and S100a9 are not only important activators of the ComC in the MBL-dependent pathway but in parallel also trigger activation of the coagulation cascade (CoaC) [ 8 , 13 , 35 ]. To explain this, DAMPs bind to MBL that subsequently triggers mannan-activated serine proteases (MASPs) to activate both ComC and in parallel also CoaC.…”

Section: Discussionmentioning

confidence: 99%

The Nlrp3 Inflammasome Orchestrates Mobilization of Bone Marrow-Residing Stem Cells into Peripheral Blood

Lenkiewicz

Adamiak

Thapa

et al. 2019

Stem Cell Rev and Rep

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Mobilization of stem cells from bone marrow (BM) into peripheral blood (PB) in response to tissue or organ injury, infections, strenuous exercise, or mobilization-inducing drugs is as we postulated result of a “sterile inflammation” in the BM microenvironment that triggers activation of the Complement Cascade (ComC). Therefore, we became interested in the role of the Nlrp3 inflammasome in this process and show for the first time that its activation in ATP-dependent manner orchestrates BM egress of hematopoietic stem/progenitor cells (HSPCs) as well as other stem cells, including mesenchymal stroma cells (MSCs), endothelial progenitor cells (EPCs), and very small embryonic-like stem cells (VSELs). To explain this extracellular ATP is a potent activator of the Nrlp3 inflammasome, which leads to the release of interleukin 1β and interleukin 18, as well as several danger-associated molecular pattern molecules (DAMPs) that activate the mannan-binding lectin (MBL) pathway of the ComC, from cells of the innate immunity network. In support of this mechanism, we demonstrate that the Nlrp3 inflammasome become activated in innate immunity cells by granulocyte colony stimulating factor (G-CSF) and AMD3100 in an ATP-dependent manner. Moreover, administration of the Nlrp3 inflammasome activator nigericin induces mobilization in mice, and the opposite effect is obtained by administration of an Nlrp3 inhibitor (MCC950) to mice mobilized by G-CSF or AMD3100. In summary, our results further support the crucial role of innate immunity, BM sterile inflammation, and novel role of the ATP–Nlrp3–ComC axis in the egress of stem cells into PB.

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Section: Discussionmentioning

confidence: 99%

The Nlrp3 Inflammasome Orchestrates Mobilization of Bone Marrow-Residing Stem Cells into Peripheral Blood

Lenkiewicz

Adamiak

Thapa

et al. 2019

Stem Cell Rev and Rep

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“…Hemostasis and coagulation occur as early as 1 hour after implantation and onset of granulation tissue development at the injury site seen within 2 hours . Nguyen et al observed the expression of coagulation factors and extrinsic coagulation initiator tissue factor by osteoblasts. This study further demonstrated the previously unknown regulatory role of such extravascular coagulation factors on the endosteal stem cell niche and the activation of their egress to areas of injury.…”

Section: The Living Bone and The Endosteal‐implant Interfacementioning

confidence: 99%

Orthopaedic osseointegration: Implantology and future directions

Overmann

Aparicio

Richards

et al. 2020

Journal Orthopaedic Research

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Osseointegration (OI) is the direct anchorage of a metal implant into bone, allowing for the connection of an external prosthesis to the skeleton. Osseointegration was first discovered in the 1960s based on the microscopic analysis of titanium implant placed into host bone. New bone was observed to attach directly to the metal surface. Following clinical investigations into dentistry applications, OI was adapted to treat extremity amputations. These bone anchored implants, which penetrate the skin and soft tissues, eliminate many of the challenges of conventional prosthetic sockets, such as poor fit and suspension, skin breakdown, and pain. Osseointegrated implants show promise to improve prosthesis use, pain, and function for amputees. The successful process of transcutaneous metal integration into host bone requires three synergistic systems: the host bone, the metal implant, and the skin‐implant interface. All three systems must be optimized for successful incorporation and longevity of the implant. Osseointegration begins during surgical implantation of the metal components through a complex interplay of cellular mechanisms. While implants can vary in design—including the original screw, press fit implants, and compressive osseointegration—they face common challenges to successful integration and maintenance of fixation within the host bone. Overcoming these challenges requires the understanding of the complex interactions between each element of OI. This review outlines (a) the basic components of OI, (b) the science behind both the bone‐implant and the skin‐implant interfaces, (c) the current challenges of OI, and (d) future opportunities within the field.

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“…Proteins like factor XI, XII, and prothrombin have been demonstrated in extravascular localizations including atherosclerotic vessels, but whether these are deposited or locally synthesized remains unknown (Borissoff et al 2010;Wilcox 1994;Soardi et al 1961). Of interest, coagulation enzymes including thrombin and aPC participate in the control of hematopoiesis in the bone marrow (Nguyen et al 2018), which may be relevant for the response to stress situations including inflammation. Within atherosclerotic lesions, coagulation proteins like TF and factors VII and X contribute to form catalytic complexes driving thrombin and fibrin formation (Borissoff et al 2010).…”

Section: Coagulation Proteasesmentioning

confidence: 99%

Antithrombotic Therapy: Prevention and Treatment of Atherosclerosis and Atherothrombosis

Olie

Meijden

Spronk

et al. 2020

Handbook of Experimental Pharmacology

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Atherosclerosis is a multifactorial vascular disease that develops in the course of a lifetime. Numerous risk factors for atherosclerosis have been identified, mostly inflicting pro-inflammatory effects. Vessel injury, such as occurring during erosion or rupture of atherosclerotic lesions triggers blood coagulation, in attempt to maintain hemostasis (protect against bleeding). However, thrombo-inflammatory mechanisms may drive blood coagulation such that thrombosis develops, the key process underlying myocardial infarction and ischemic stroke (not due to embolization from the heart). In the blood coagulation system, platelets and coagulation proteins are both essential elements. Hyperreactivity of blood coagulation aggravates atherosclerosis in preclinical models. Pharmacologic inhibition of blood coagulation, either with platelet inhibitors, or better documented with anticoagulants, or both, limits the risk of thrombosis and may potentially reverse atherosclerosis burden, although the latter evidence is still based on animal experimentation. Patients at risk of atherothrombotic complications should receive a single antiplatelet agent (acetylsalicylic acid, ASA, or clopidogrel); those who survived an atherothrombotic event will be prescribed temporary dual antiplatelet therapy (ASA plus a P2Y12 inhibitor) in case of myocardial infarction (6-12 months), or stroke (<6 weeks), followed by a single antiplatelet agent indefinitely. High risk for thrombosis patients (such as those with peripheral artery disease) benefit from a combination of an anticoagulant and ASA. The price of gained efficacy is always increased risk of (major) bleeding; while tailoring therapy to individual needs may limit the risks to some extent, new generations of agents that target less critical elements of hemostasis and coagulation mechanisms are needed to maintain efficacy while reducing bleeding risks.

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Extravascular coagulation in hematopoietic stem and progenitor cell regulation

Cited by 39 publications

References 103 publications

The Nlrp3 Inflammasome Orchestrates Mobilization of Bone Marrow-Residing Stem Cells into Peripheral Blood

The Nlrp3 Inflammasome Orchestrates Mobilization of Bone Marrow-Residing Stem Cells into Peripheral Blood

Orthopaedic osseointegration: Implantology and future directions

Antithrombotic Therapy: Prevention and Treatment of Atherosclerosis and Atherothrombosis

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