Treating chronic GVHD-induced fibrosis?

Socié, Gérard

doi:10.1182/blood-2018-02-830505

Cited by 7 publications

(5 citation statements)

References 9 publications

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“…While acute form of the GVBD is caused by the T cells, B cells, the chronic GVBD mostly depend on macrophages. Activated macrophages infiltrate various organs and tissues and produce transforming growth factorβ (TGF-β), leading to fibroblast activation and overproduction of collagen [23][24][25]. Belumosudil, through inhibition of the RhoA/ROCK pathway, reduces cGVBD fibrosis by downregulating TGF-β signaling and inhibiting the expression of profibrotic genes and collagen production [26].…”

Section: Clinically Approved Therapies With Fingolimod and Belumosudilmentioning

confidence: 99%

Repurposing of multiple sclerosis (MS) and graft versus host disease (GVHD) therapeutics to inhibit chronic rejection of transplanted organs

Kloc,

Uosef,

Halasa

2023

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Chronic rejection of transplanted organs is an incurable event in transplantation. Macrophages infiltrating allograft induce vessel occlusion and tissue fibrosis, which over the months-years post-transplantation cause organ failure. Patients require re-transplantation, which is extremely problematic because of the permanent lack of organ donors. Our studies showed that chronic rejection depends on the function of macrophages and the RhoA/ROCK pathway. Genetic (RhoA knockout) or pharmacologic (ROCK inhibitors) interference with the RhoA pathway inhibits macrophage functions and prevents chronic rejection in the rodent transplantation model. Most commercially available RhoA pathway inhibitors are not approved for clinical use. However, we found two compounds: fingolimod (Gilenya, FTY720) and belumosudil (Rezurock), which are clinically approved for relapsing multiple sclerosis (MS) and chronic graft versus host disease (cGVHD), respectively, which also inhibit the RhoA pathway. We tested these two drugs in the rodent transplantation model, and both inhibited chronic rejection. Thus, we proposed to repurpose these drugs for organ transplantation. A clinical trial on the effect of fingolimod in kidney transplant patients is ongoing, and the belumosudil trial is pending.

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Section: Clinically Approved Therapies With Fingolimod and Belumosudilmentioning

confidence: 99%

Repurposing of multiple sclerosis (MS) and graft versus host disease (GVHD) therapeutics to inhibit chronic rejection of transplanted organs

Kloc,

Uosef,

Halasa

2023

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“…Allogenic ADMSC-EVs reduced the CCl 4 -induced collagen volume fraction and α-SMA/collagen I/III expression by transferring miR-150-5p to inhibit CXCL1 signaling in a mouse CCl 4 model ( 87 ). Chronic graft-versus-host disease (cGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation and is highly associated with major organ damage, such as liver damage ( 132 , 133 ). In cGVHD mice, hBMSC-EVs alleviated the degree of liver fibrosis and prolonged animal survival by inducing IL-10 + regulatory cells and inhibiting IL-17 + pathogenic T cells ( 88 ).…”

Section: Therapeutic Potential Of Native Evsmentioning

confidence: 99%

Extracellular vesicles as advanced therapeutics for the resolution of organ fibrosis: Current progress and future perspectives

Wang

Lou

et al. 2022

Front. Immunol.

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Organ fibrosis is a serious health challenge worldwide, and its global incidence and medical burden are increasing dramatically each year. Fibrosis can occur in nearly all major organs and ultimately lead to organ dysfunction. However, current clinical treatments cannot slow or reverse the progression of fibrosis to end-stage organ failure, and thus advanced anti-fibrotic therapeutics are urgently needed. As a type of naturally derived nanovesicle, native extracellular vesicles (EVs) from multiple cell types (e.g., stem cells, immune cells, and tissue cells) have been shown to alleviate organ fibrosis in many preclinical models through multiple effective mechanisms, such as anti-inflammation, pro-angiogenesis, inactivation of myofibroblasts, and fibrinolysis of ECM components. Moreover, the therapeutic potency of native EVs can be further enhanced by multiple engineering strategies, such as genetic modifications, preconditionings, therapeutic reagent-loadings, and combination with functional biomaterials. In this review, we briefly introduce the pathology and current clinical treatments of organ fibrosis, discuss EV biology and production strategies, and particularly focus on important studies using native or engineered EVs as interventions to attenuate tissue fibrosis. This review provides insights into the development and translation of EV-based nanotherapies into clinical applications in the future.

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“…Briefly, the pathophysiology of GvHD includes pre-transplant host tissue damage, followed by activation of donor T-cells and inflammatory factor release which results in amplified tissue damage [92,93]. This ultimately results in widespread inflammation and multiorgan system fibrosis [94]. One of the greatest challenges of GvHD is its nearly identical symptomatic presentation and appearance on most imaging devices to colitis.…”

Section: Graft Versus Host Diseasementioning

confidence: 99%

Advances in Imaging of Inflammation, Fibrosis, and Cancer in the Gastrointestinal Tract

Harold

MacCuaig

Holter-Charkabarty

et al. 2022

IJMS

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Gastrointestinal disease is prevalent and broad, manifesting itself in a variety of ways, including inflammation, fibrosis, infection, and cancer. However, historically, diagnostic technologies have exhibited limitations, especially with regard to diagnostic uncertainty. Despite development of newly emerging technologies such as optoacoustic imaging, many recent advancements have focused on improving upon pre-existing modalities such as ultrasound, computed tomography, magnetic resonance imaging, and endoscopy. These advancements include utilization of machine learning models, biomarkers, new technological applications such as diffusion weighted imaging, and new techniques such as transrectal ultrasound. This review discusses assessment of disease processes using imaging strategies for the detection and monitoring of inflammation, fibrosis, and cancer in the context of gastrointestinal disease. Specifically, we include ulcerative colitis, Crohn’s disease, diverticulitis, celiac disease, graft vs. host disease, intestinal fibrosis, colorectal stricture, gastric cancer, and colorectal cancer. We address some of the most recent and promising advancements for improvement of gastrointestinal imaging, including unique discussions of such advancements with regard to imaging of fibrosis and differentiation between similar disease processes.

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Treating chronic GVHD-induced fibrosis?

Cited by 7 publications

References 9 publications

Repurposing of multiple sclerosis (MS) and graft versus host disease (GVHD) therapeutics to inhibit chronic rejection of transplanted organs

Repurposing of multiple sclerosis (MS) and graft versus host disease (GVHD) therapeutics to inhibit chronic rejection of transplanted organs

Extracellular vesicles as advanced therapeutics for the resolution of organ fibrosis: Current progress and future perspectives

Advances in Imaging of Inflammation, Fibrosis, and Cancer in the Gastrointestinal Tract

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