Impaired hematopoietic progenitor cells in trauma hemorrhagic shock

Kumar, Manoj; Bhoi, Sanjeev

doi:10.1016/j.jcot.2016.05.013

Cited by 10 publications

(11 citation statements)

References 32 publications

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“…Activity of the bone marrow has been shown to be altered by trauma in patients. Severe trauma induces endothelial hyperpermeability, hematopoietic stem and progenitor cell trafficking, anemia, inflammation, compensatory immunosuppression, and bone marrow dysfunction 56,57 . Specifically, Livingston and colleagues have described bone marrow failure, including reduced hematopoietic activity and severe growth defects in bone marrow stromal cells which are a critical component of the hematopoietic niche 5 .…”

Section: Discussionmentioning

confidence: 99%

Injury intensifies T cell mediated graft-versus-host disease in a humanized model of traumatic brain injury

Díaz

Horton

Kumar

et al. 2020

Sci Rep

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The immune system plays critical roles in promoting tissue repair during recovery from neurotrauma but is also responsible for unchecked inflammation that causes neuronal cell death, systemic stress, and lethal immunodepression. Understanding the immune response to neurotrauma is an urgent priority, yet current models of traumatic brain injury (TBI) inadequately recapitulate the human immune response. Here, we report the first description of a humanized model of TBI and show that TBI places significant stress on the bone marrow. Hematopoietic cells of the marrow are regionally decimated, with evidence pointing to exacerbation of underlying graft-versus-host disease (GVHD) linked to presence of human T cells in the marrow. Despite complexities of the humanized mouse, marrow aplasia caused by TBI could be alleviated by cell therapy with human bone marrow mesenchymal stromal cells (MSCs). We conclude that MSCs could be used to ameliorate syndromes triggered by hypercytokinemia in settings of secondary inflammatory stimulus that upset marrow homeostasis such as TBI. More broadly, this study highlights the importance of understanding how underlying immune disorders including immunodepression, autoimmunity, and GVHD might be intensified by injury. Traumatic brain injury (TBI) is a major contributor to long-term disability and mortality in children and adults, and, despite intensive efforts, there are no effective treatments for TBI 1,2. Sequelae of TBI and soft tissue injuries resulting from polytrauma include changes in cerebral metabolism, excitotoxicity, induction of emergency hematopoiesis, infiltration of fluid and inflammatory cells into the brain, systemic cytokine storm and localized cytokine release, and activation of microglia, the resident macrophage of the central nervous system 3-8. The immune system plays critical roles in promoting tissue repair and clearance of dying neurons during recovery from neurotrauma but is also responsible for the deleterious inflammation that kills healthy neurons. Systemic immunodepression and vulnerability to infection often follow the acute phase of TBI wherein hypercytokinemia and inflammation resolve, placing patients at increased risk of pneumonia and sepsis 9. Thus, understanding the contribution of the immune system to recovery is critical to development of efficacious therapies for neurotrauma 10,11 .

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Section: Discussionmentioning

confidence: 99%

Injury intensifies T cell mediated graft-versus-host disease in a humanized model of traumatic brain injury

Díaz

Horton

Kumar

et al. 2020

Sci Rep

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“…The sympathetic nervous system, which regulates the body's response to trauma, can directly interact with immune cells through adrenergic receptors . Trauma, HS, and subsequent release of proinflammatory cytokines can result in a sustained increase in circulatory norepinephrine, which can suppress the growth and differentiation of hematopoietic progenitors, particularly erythroid progenitors, and facilitate their mobilization out of the bone marrow . Blocking the adrenergic receptors in Sprague–Dawley rats was shown to restore progenitor function .…”

Section: Discussionmentioning

confidence: 99%

Flow Cytometric Analysis of Hematopoietic Populations in Rat Bone Marrow. Impact of Trauma and Hemorrhagic Shock

et al. 2019

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Severe injury and hemorrhagic shock (HS) result in multiple changes to hematopoietic differentiation, which contribute to the development of immunosuppression and multiple organ failure (MOF). Understanding the changes that take place during the acute injury phase may help predict which patients will develop MOF and provide potential targets for therapy. Obtaining bone marrow from humans during the acute injury phase is difficult so published data are largely derived from peripheral blood samples, which infer bone marrow changes that reflect the sustained inflammatory response. This preliminary and opportunistic study investigated leucopoietic changes in rat bone marrow 6 h following traumatic injury and HS. Terminally anesthetized male Porton Wistar rats were allocated randomly to receive a sham operation (cannulation with no injury) or femoral fracture and HS. Bone marrow cells were flushed from rat femurs and immunophenotypically stained with specific antibody panels for lymphoid (CD45R, CD127, CD90, and IgM) or myeloid (CD11b, CD45, and RP‐1) lineages. Subsequently, cell populations were fluorescence‐activated cell sorted for morphological assessment. Stage‐specific cell populations were identified using a limited number of antibodies, and leucopoietic changes were determined 6 h following trauma and HS. Myeloid subpopulations could be identified by varying levels CD11b expression, CD45, and RP‐1. Trauma and HS resulted in a significant reduction in total CD11b + myeloid cells including both immature (RP‐1(−)) and mature (RP‐1+) granulocytes. Multiple B‐cell lymphoid subsets were identified. The total percentage of CD90+ subsets remained unchanged following trauma and HS, but there was a reduction in the numbers of maturing CD90(−) cells suggesting movement into the periphery. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

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“…1 , 2 Recent studies shown mobilization of HPCs from BM in peripheral blood cells associated with the poor outcome in patients with T/HS. 1 Multiple factors are involved in the HF and not just the mobilization of HPCs from bone marrow in to peripheral blood. Elevated cytokines, Granulocyte colony stimulating factor (G-CSF), norepinephrine levels and decreased the expression of erythropoietin receptor (EpoR) also contributed the hematopoietic failure in T/HS Patients (Fig.…”

Section: Hematopoietic Failure and T/hsmentioning

confidence: 99%

“…Elevated serum cytokines (TNF-a, IL-6) levels, granulocyte colony stimulating factor (G-CSF), catecholamine, mobilization of hematopoietic progenitor cells (HPCs) from bone marrow in to peripheral blood cells and decreased expression of erythropoietin (EPO-R) receptor are also associated with HF among T/HS. 1 , 2 Advanced care and treatment of the traumatic injured and haemorrhage patients has undergone much progress in the last decades. Resuscitation fluid, blood and its components are used for the control of haemorrhage.…”

Section: Introductionmentioning

confidence: 99%

Human-induced pluripotent stem cells derived hematopoietic progenitor cells for treatment of hematopoietic failure among trauma hemorrhagic shock patients

Kumar

Bhoi

Sharma

2019

Journal of Clinical Orthopaedics and Trauma

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Hematopoietic failure (HF) has been observed in trauma hemorrhagic shock (T/HS) patients. Multiple factors are involved. Elevated serum levels of cytokines, catecholamine, granulocyte colony stimulating factor, peripheral blood hematopoietic progenitor cells (HPCs) and decreased expression of erythropoietin receptor are associated with HF among T/HS. HF leads to anaemia, susceptibility to infection, sepsis and multi-organ failure. There is a lack of molecular understanding of HF and its potential therapeutic strategies. Cell-based therapy has ability to modulate the production of inflammatory cytokines, vascular dysfunction, tissue damage and apoptosis. Human-induced pluripotent stem cells (iPSC) derived HPCs may have the ability to restore HF in T/HS. Autologous cell-based iPSC have great promises for various diseases such as Alzheimer's disease, Parkinson's disease, cardiovascular disease, diabetes, amyotrophic lateral sclerosis, and spinal cord injury without ethical concerns. Similarly, treatment with iPSC derived hematopoietic stem cells can used for the treatment of HF among T/HS and may also improve the outcome. Here, we review the potential of human iPSC derived HSC to reversed HF following T/HS.

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Impaired hematopoietic progenitor cells in trauma hemorrhagic shock

Cited by 10 publications

References 32 publications

Injury intensifies T cell mediated graft-versus-host disease in a humanized model of traumatic brain injury

Injury intensifies T cell mediated graft-versus-host disease in a humanized model of traumatic brain injury

Flow Cytometric Analysis of Hematopoietic Populations in Rat Bone Marrow. Impact of Trauma and Hemorrhagic Shock

Human-induced pluripotent stem cells derived hematopoietic progenitor cells for treatment of hematopoietic failure among trauma hemorrhagic shock patients

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