Search results for " transplantation"

Modulating endothelial adhesion and migration impacts stem cell therapies efficacy

2020

Abstract Background Limited knowledge of stem cell therapies` mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested whether adhesion receptors and chemokine receptors on stem cells can be functionally modulated, and consequently if such modulation may substantially affect therapeutically relevant stem cell interactions with the host endothelium. Methods We investigated the effects of cationic molecule polyethylenimine (PEI) treatment with or without nanoparticles on the functions of adhesion receptors a…

2017

Human Cytomegalovirus (CMV) can lead to primary infection or reactivation in CMV-seronegative or -seropositive kidney transplant recipients, respectively. Complications comprise severe end-organ diseases and acute or chronic transplant rejection. Risk for CMV manifestation is stratified according to the CMV-IgG-serostatus, with donor+/recipient- (D+/R-) patients carrying the highest risk for CMV-replication. However, risk factors predisposing for primary infection in CMV-seronegative recipients are still not fully elucidated. Therefore, we monitored D+/R- high-risk patients undergoing kidney transplantation in combination with antiviral prophylaxis for the incidence of CMV-viremia for a med…

Mouse Model of Cytomegalovirus Disease and Immunotherapy in the Immunocompromised Host: Predictions for Medical Translation that Survived the “Test o…

2018

Human Cytomegalovirus (hCMV), which is the prototype member of the β-subfamily of the herpesvirus family, is a pathogen of high clinical relevance in recipients of hematopoietic cell transplantation (HCT). hCMV causes multiple-organ disease and interstitial pneumonia in particular upon infection during the immunocompromised period before hematopoietic reconstitution restores antiviral immunity. Clinical investigation of pathomechanisms and of strategies for an immune intervention aimed at restoring antiviral immunity earlier than by hematopoietic reconstitution are limited in patients to observational studies mainly because of ethical issues including the imperative medical indication …

Influence of gut microbiota on neuropsychiatric disorders

2017

The last decade has witnessed a growing appreciation of the fundamental role played by an early assembly of a diverse and balanced gut microbiota and its subsequent maintenance for future health of the host. Gut microbiota is currently viewed as a key regulator of a fluent bidirectional dialogue between the gut and the brain (gut-brain axis). A number of preclinical studies have suggested that the microbiota and its genome (microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson’s dis…

Extravascular coagulation in hematopoietic stem and progenitor cell regulation

2018

Abstract The hemostatic system plays pivotal roles in injury repair, innate immunity, and adaptation to inflammatory challenges. We review the evidence that these vascular-protective mechanisms have nontraditional roles in hematopoietic stem cell (HSC) maintenance in their physiological bone marrow (BM) niches at steady-state and under stress. Expression of coagulation factors and the extrinsic coagulation initiator tissue factor by osteoblasts, tissue-resident macrophages, and megakaryocytes suggests that endosteal and vascular HSC niches are functionally regulated by extravascular coagulation. The anticoagulant endothelial protein C receptor (EPCR; Procr) is highly expressed by primitive …

Donor interleukin-22 and host type I interferon signaling pathway participate in intestinal graft-versus-host disease via STAT1 activation and CXCL10.

2014

Acute graft-versus-host disease (aGVHD) remains a major complication following allogeneic hematopoietic cell transplantation, limiting the success of this therapy. We previously reported that interleukin-22 (IL-22) participates to aGVHD development, but the underlying mechanisms of its contribution remain poorly understood. In this study, we analyzed the mechanism of the pathological function of IL-22 in intestinal aGVHD. Ex-vivo colon culture experiments indicated that IL-22 was able to induce Th1-like inflammation via signal transducer and activator of transcription factor-1 (STAT1) and CXCL10 induction in the presence of type I interferon (IFN). To evaluate a potential synergy between IL…

Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion

2015

Activation of TNFR2 with a novel agonist expands T reg cells in vivo and protects allo-HCT recipients from acute GvHD while sparing antilymphoma and antiinfectious properties of transplanted donor T cells.

Electrospun poly(hydroxybutyrate) scaffolds promote engraftment of human skin equivalents via macrophage M2 polarization and angiogenesis.

2018

Human dermo-epidermal skin equivalents (DE) comprising in vitro expanded autologous keratinocytes and fibroblasts are a good option for massive burn treatment. However, the lengthy expansion time required to obtain sufficient surface to cover an extensive burn together with the challenging surgical procedure limits their clinical use. The integration of DE and biodegradable scaffolds has been proposed in an effort to enhance their mechanical properties. Here, it is shown that poly(hydroxybutyrate) electrospun scaffolds (PHB) present good biocompatibility both in vitro and in vivo and are superior to poly-epsilon-caprolactone electrospun scaffolds as a substrate for skin reconstruction. Impl…

Protein tyrosine phosphatase 1b deficiency protects against hepatic fibrosis by modulating nadph oxidases

2019

Inflammation is typically associated with the development of fibrosis, cirrhosis and hepatocellular carcinoma. The key role of protein tyrosine phosphatase 1B (PTP1B) in inflammatory responses has focused this study in understanding its implication in liver fibrosis. Here we show that hepatic PTP1B mRNA expression increased after bile duct ligation (BDL), while BDL-induced liver fibrosis was markedly reduced in mice lacking Ptpn1 (PTP1B−/−) as assessed by decreased collagen deposition and α-smooth muscle actin (α-SMA) expression. PTP1B−/− mice also showed a significant increase in mRNA levels of key markers of monocytes recruitment (Cd68, Adgre1 and Ccl2) compared to their wild-type (PTP1B+…

3d collagen hydrogel promotes in vitro langerhans islets vascularization through ad-mvfs angiogenic activity

2021

Adipose derived microvascular fragments (ad-MVFs) consist of effective vascularization units able to reassemble into efficient microvascular networks. Because of their content in stem cells and related angiogenic activity, ad-MVFs represent an interesting tool for applications in regenerative medicine. Here we show that gentle dissociation of rat adipose tissue provides a mixture of ad-MVFs with a length distribution ranging from 33–955 μm that are able to maintain their original morphology. The isolated units of ad-MVFs that resulted were able to activate transcriptional switching toward angiogenesis, forming tubes, branches, and entire capillary networks when cultured in 3D collagen type-…