Inflammatory Cytokine Networks in Gastrointestinal Tract Graft vs. Host Disease

Piper, Clint; Drobyski, William R.

doi:10.3389/fimmu.2019.00163

Cited by 34 publications

(33 citation statements)

References 100 publications

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“…T cells are chief contributors to manifestation and severity of GVHD and act by secreting cytokines that lead to disease onset, especially in the context of cytokine storm 67,68 such as that observed in TBI. Here, we show that bone marrow phenotype correlates tightly with T cell abundance.…”

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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“…MSCs and their derivative exosomes have long been known for their immune-modulatory potential and thus have been evaluated in various pre-clinical and clinical settings. A noteworthy, similar condition is observed in Graft versus host disease (GvHD) associated pulmonary disease [56,57]. In a preliminary clinical study, MSC-exosomes were shown to alleviate the symptoms of grade IV GvHD patients [58].…”

Section: Therapeutic Role Of Msc Derived Exosomes In Lung Diseasesmentioning

confidence: 67%

Mesenchymal Stem Cell Derived Exosomes: a Nano Platform for Therapeutics and Drug Delivery in Combating COVID-19

Pinky

Gupta

Krishnakumar

et al. 2020

Stem Cell Rev and Rep

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The recent pandemic situation transpired due to coronavirus novel strain SARS-CoV-2 has become a global concern. This human coronavirus (HCov-19) has put the world on high alert as the numbers of confirmed cases are continuously increasing. The world is now fighting against this deadly virus and is leaving no stone unturned to find effective treatments through testing of various available drugs, including those effective against flu, malaria, etc. With an urgent need for the development of potential strategies, two recent studies from China using Mesenchymal Stem Cells (MSCs) to treat COVID-19 pneumonia have shed some light on a potential cure for the COVID-19 infected patients. However, MSCs, despite being used in various other clinical trials have always been questioned for their tendency to aggregate or form clumps in the injured or disease microenvironment. It has also been reported in various studies that exosomes secreted by these MSCs, contribute towards the cell's biological and therapeutic efficacy. There have been reports evaluating the safety and feasibility of these exosomes in various lung diseases, thereby proposing them as a cell-free therapeutic agent. Also, attractive features like cell targeting, low-immunogenicity, safety, and high biocompatibility distinguish these exosomes from other synthetic nano-vesicles and thus potentiate their role as a drug delivery nano-platform. Building upon these observations, herein, efforts are made to give an overview of stem cell-derived exosomes as an appealing therapeutic agent and drug delivery nano-carrier. In this review, we briefly recapitulate the recent evidence and developments in understanding exosomes as a promising candidate for novel nano-intervention in the current pandemic scenario. Furthermore, this review will highlight and discuss mechanistic role of exosomes to combat severe lung pathological conditions. We have also attempted to dwell into the nano-formulation of exosomes for its better applicability, storage, and stability thereby conferring them as off the shelf therapeutic.

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“…We combined treosulfan with fludarabine, thymoglobulin, and cyclophosphamide (60 mg/kg × 2 doses), resulting in a transplant preparative regimen that was lower in intensity than Conv MA regimens but stronger than the previous RIC regimen 9 . Pro‐inflammatory cytokines during HSCT have been associated with adverse outcomes 12‐14 . In animal studies, treosulfan has shown to cause lower levels of inflammatory cytokines compared to busulfan and cyclophosphamide, which may provide an additional advantage in particular in patients with HLH.…”

Section: Discussionmentioning

confidence: 99%

Effect of different conditioning regimens on survival and engraftment for children with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoeitic stem cell transplantation: A single institution experience

Ali

Wall

Ali

et al. 2020

Pediatric Blood & Cancer

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Background Hemophagocytic lymphohistiocytosis (HLH), a rare hyperinflammatory immuneregulatory disorder, is a challenge in hematopoietic stem cell transplantation (HSCT) because of the high rate of mixed chimerism, relapse, and graft failure (GF) unless intensive myeloablative regimens are used. However, historically conventional myeloablative regimens (conv MA) are associated with high toxicity and mortality. Procedure We retrospectively compared transplant outcomes between three preparative regimens of varying intensities: Conv MA (n = 15), reduced‐intensity conditioning (RIC, n = 12), and a treosulfan‐based reduced‐toxicity conditioning (RTC, n = 9). Results Patients in the RIC cohort had a higher incidence of mixed donor chimerism and five patients (42%) developed secondary GF (P = .002) compared to the other two regimens. There was a higher incidence of veno‐occlusive disease and intensive care unit (ICU) admissions in the Conv MA cohort. With the RTC regimen, there was a similar 2‐year overall survival (89, 73, and 83%; P = .87), but improved compound EFS (lack of relapse, GF, second transplant or additional donor cell infusions, or death; 89, 73, and 42%, P = .041) in RTC, Conv MA, and RIC regimen, respectively. Conclusions The intensity of the preparative regimen has a significant impact on outcome of HSCT for HLH. The newly described treosulfan‐based RTC provides for a stable graft with a reasonable toxicity profile.

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Inflammatory Cytokine Networks in Gastrointestinal Tract Graft vs. Host Disease

Cited by 34 publications

References 100 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

Mesenchymal Stem Cell Derived Exosomes: a Nano Platform for Therapeutics and Drug Delivery in Combating COVID-19

Effect of different conditioning regimens on survival and engraftment for children with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoeitic stem cell transplantation: A single institution experience

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