scholarly journals Adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jingting Chen ◽  
Yinmin Wang ◽  
Haoyue Hu ◽  
Yao Xiong ◽  
Shoubao Wang ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Graft Survival ◽  
Hind Limb ◽  
Ex Vivo ◽  
Stromal Vascular Fraction ◽  
Term Survival ◽  
Cellular Therapies ◽  
The Impact ◽  
Prolong Graft Survival ◽  
Transplantation Model

Abstract Background The long-term survival after vascularized composite allotransplantation (VCA) is often limited by systemic rejection as well as the adverse effects of immunosuppressants. The stromal vascular fraction (SVF) can be expanded to produce adipose-derived stem cells (ADSC) which represents a combination of endothelial cells, preadipocytes, immune cells, and ADSC. It has been demonstrated that ADSC possess consistently reliable clinical results. However, literature is scarce regarding SVF in VCA. This study seeks to determine the impact of ex vivo allograft pretreatment in combination with SVF cells in the ability to promote composite tissue allotransplantation immunotolerance. Methods A rat hind limb allotransplant model was used to investigate the influence of ex vivo pretreatment of SVF and ADSC on VCA survival. Intravascular cell-free saline, ADSC, or SVF was infused into the models with immunosuppressants. The histopathological examination and duration that the allografts went without displaying symptoms of rejection was documented. Peripheral T lymphocytes and Tregs were quantified with flow cytometry while allotissue expressions of CD31 were quantified with immunohistochemical staining (IHC). ELISA was used to detect vascular endothelial growth factor (VEGF)-A as well as anti- and pro-inflammatory cytokines. Results We demonstrated that ex vivo treatment of allografts with SVF or ADSC prolonged allograft survival in contrast to medium control cohorts. There were also enhanced levels of immunomodulatory cytokines and increased VEGF-A and CD31 expression as well as reduced infiltration and proliferation of T lymphocytes along with raised Treg expressions. Conclusion These studies demonstrated that adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model and have the potential to establish immunotolerance.

The impact of sarcopenia and myosteatosis in liver transplant candidates on peritransplant course and patient and graft survival

2021 ◽  
Vol 75 (4) ◽  
pp. 311-322
Author(s):  
Irena Míková ◽  
Denisa Kyselová ◽  
Dana Kautznerová ◽  
Marek Tupý ◽  
Marek Kysela ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Graft Survival ◽  
Blood Transfusions ◽  
Term Survival ◽  
Skeletal Muscle Index ◽  
Long Term Survival ◽  
Psoas Major Muscle ◽  
The Impact ◽  
Patient And Graft Survival

Introduction: Sarcopenia (severe muscle depletion) and myosteaosis (pathological fat accumulation in muscle) are frequent muscle abnormalities in patients with cirrhosis associated with unfavorable prognosis. The aim of our study was to evaluate the impact of sarcopenia and myosteatosis in liver transplant (LT) candidates in our center on the peritransplant course and patient and graft survival. Methods: This prospective study included adult LT candidates who underwent clinical and laboratory examination. The skeletal muscle index (SMI) at L3 level and radiodensity of psoas major muscle (PM-RA) were evaluated by CT. Results: Pretransplant sarcopenia was found in 49 of 103 patients (47.6%) and myosteatosis in 53 (51.5%) patients. Patients with sarcopenia had lower BMI, waist circumference, occurrence of hypertension and metabolic syndrome and lower triglyceride and C-peptide levels than patients without sarcopenia. Patients with myosteatosis had higher Child-Pugh score and lower HDL-cholesterol levels than patients without myosteatosis. Pretransplant SMI negatively correlated with the amount of blood transfusions given during LT and occurrence of biliary complications. Patients with myosteatosis had higher need for blood transfusions during LT and after LT, and higher number of surgical revisions. Occurrence of sarcopenia had no significant effect on patient and graft survival. Patients with myosteatosis had worse long-term survival than patients without myosteatosis, the graft survival did not differ. Conclusion: Sarcopenia and myosteatosis are frequent muscle abnormalities in LT candidates with negative impact on peritransplant course. Myosteatosis was associated with a worse long-term survival in our study. Key words: sarcopenia – myosteatosis – liver transplantation – prevalence – complications – survival

scholarly journals The Prognostic Impact of Circulating Regulatory T Lymphocytes on Mortality in Patients with Ischemic Heart Failure with Reduced Ejection Fraction

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Andreas Hammer ◽  
Patrick Sulzgruber ◽  
Lorenz Koller ◽  
Niema Kazem ◽  
Felix Hofer ◽  
...  
Keyword(s):  
Heart Failure ◽  
T Lymphocytes ◽  
Ejection Fraction ◽  
Cellular Immunity ◽  
Prognostic Impact ◽  
Inverse Association ◽  
Term Survival ◽  
Reduced Ejection Fraction ◽  
Regulatory T Lymphocytes ◽  
The Impact

Background. Heart failure with reduced ejection fraction (HFrEF) constitutes a global health issue. While proinflammatory cytokines proved to have a pivotal role in the development and progression of HFrEF, less attention has been paid to the cellular immunity. Regulatory T lymphocytes (Tregs) seem to have an important role in the induction and maintenance of immune homeostasis. Therefore, we aimed to investigate the impact of Tregs on the outcome in HFrEF. Methods. We prospectively enrolled 112 patients with HFrEF and performed flow cytometry for cell phenotyping. Individuals were stratified in ischemic (iHFrEF, n=57) and nonischemic etiology (niHFrEF, n=55). Cox regression hazard analysis was used to assess the influence of Tregs on survival. Results. Comparing patients with iHFrEF to niHFrEF, we found a significantly lower fraction of Tregs within lymphocytes in the ischemic subgroup (0.42% vs. 0.56%; p=0.009). After a mean follow-up time of 4.5 years, 32 (28.6%) patients died due to cardiovascular causes. We found that Tregs were significantly associated with cardiovascular survival in the entire study cohort with an adjusted HR per one standard deviation (1-SD) of 0.60 (95% CI: 0.39-0.92; p=0.017). A significant inverse association of Tregs and cardiovascular mortality in patients with iHFrEF with an adj. HR per 1-SD of 0.59 (95% CI: 0.36-0.96; p=0.034) has been observed, while this association was not evident in the nonischemic subgroup (adj. HR per 1-SD of 0.62 (95% CI: 0.17-2.31); p=0.486). Conclusion. Our results indicate a potential influence of Tregs in the pathogenesis and progression of iHFrEF, fostering the implication of cellular immunity in iHFrEF pathophysiology and proving Tregs as a predictor for long-term survival among iHFrEF patients. A preview of this study has been presented at a meeting of the European Society of Cardiology earlier this year.

Quantitative Assessment of Human T Lymphocytes in RAG2−/−γc−/− Mice: The Impact of Ex Vivo Manipulation on In Vivo Functionality

2007 ◽  
Vol 35 (1) ◽  
pp. 117-127 ◽  
Author(s):  
Rozemarijn S. van Rijn ◽  
Elles R. Simonetti ◽  
Anton Hagenbeek ◽  
Mark Bonyhadi ◽  
Gert Storm ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Quantitative Assessment ◽  
Ex Vivo ◽  
Human T Lymphocytes ◽  
The Impact

Recipient bone marrow-derived stromal cells prolong graft survival in a rat hind limb allotransplantation model

Microsurgery ◽  
2016 ◽  
Vol 37 (6) ◽  
pp. 632-640 ◽  
Author(s):  
Ryosuke Ikeguchi ◽  
Ryosuke Kakinoki ◽  
Souichi Ohta ◽  
Hiroki Oda ◽  
Hirofumi Yurie ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Graft Survival ◽  
Stromal Cells ◽  
Hind Limb ◽  
Prolong Graft Survival

scholarly journals The Caspase-1/IL-18 Axis of the Inflammasome in Tumor Cells: A Modulator of the Th1/Tc1 Response of Tumor-Infiltrating T Lymphocytes in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 189
Author(s):  
Linda Bilonda Mutala ◽  
Cécile Deleine ◽  
Matilde Karakachoff ◽  
Delphine Dansette ◽  
Kathleen Ducoin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
Ex Vivo ◽  
Explant Culture ◽  
T Cell Response ◽  
Mrna Levels ◽  
Innate And Adaptive Immunity ◽  
Caspase 1 ◽  
Culture Model

In colorectal cancer (CRC), a high density of T lymphocytes represents a strong prognostic marker in subtypes of CRC. Optimized immunotherapy strategies to boost this T-cell response are still needed. A good candidate is the inflammasome pathway, an emerging player in cancer immunology that bridges innate and adaptive immunity. Its effector protein caspase-1 matures IL-18 that can promote a T-helper/cytotoxic (Th1/Tc1) response. It is still unknown whether tumor cells from CRC possess a functional caspase-1/IL-18 axis that could modulate the Th1/Tc1 response. We used two independent cohorts of CRC patients to assess IL-18 and caspase-1 expression by tumor cells in relation to the density of TILs and the microsatellite status of CRC. Functional and multiparametric approaches at the protein and mRNA levels were performed on an ex vivo CRC explant culture model. We show that, in the majority of CRCs, tumor cells display an activated and functional caspase-1/IL-18 axis that contributes to drive a Th1/Tc1 response elicited by TILs expressing IL-18Rα. Furthermore, unsupervised clustering identified three clusters of CRCs according to the caspase-1/IL-18/TIL density/interferon gamma (IFNγ) axis and microsatellite status. Together, our results strongly suggest that targeting the caspase-1/IL-18 axis can improve the anti-tumor immune response in subgroups of CRC.

scholarly journals 231 Impact of Brachyspira hyodysentariae on intestinal function and integrity

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 116-116
Author(s):  
Emma T Helm ◽  
Susanne J Lin ◽  
Nicholas Gabler ◽  
Eric R Burrough
Keyword(s):  
Ex Vivo ◽  
Potato Starch ◽  
Nutrient Digestibility ◽  
High Morbidity ◽  
Post Inoculation ◽  
Intestinal Function ◽  
Treatment Groups ◽  
Intestinal Integrity ◽  
Beet Pulp ◽  
The Impact

Abstract Swine dysentery (SD) induced by Brachyspira hyodysentariae (Bhyo) causes colitis and mucohemorrhagic diarrhea in grow-finish pigs, however little is known about the physiological changes that occur to the gastrointestinal tract during Bhyo infection. Thus, the objective of this study was to evaluate the impact of a Bhyo challenge on intestinal function and integrity of pigs fed two divergent diets. A total of 36 Bhyo negative gilts (24.3 ± 3.6 kg BW) were selected and assigned to one of three treatment groups (n=12 pigs/trt): 1) Bhyo negative, 20% DDGS diet (CON), 2) Bhyo challenged, 20% DDGS diet (DDGS), and 3) Bhyo challenged, 10% DDGS, 5% beet pulp and 5% resistant potato starch diet (RS). Pigs were fed diets 21 days prior to challenge and on days post inoculation (dpi) 0 and 1, pigs were inoculated with Bhyo or sham. Fecal samples were collected for ATTD and pigs were euthanized for colon collection within 72 hours of initial observation of clinical SD, or at the end of the study (dpi 10-16). Tissues were assessed for ex vivo measures of intestinal integrity and mitochondrial function. The challenge resulted in high morbidity, with 88% of DDGS and RS pigs developing clinical SD. Colon transepithelial resistance was increased in DDGS pigs compared with CON and RS pigs (P=0.005), and colon macromolecule permeability was reduced in both DDGS and RS pigs compared with CON pigs (P=0.006), likely due to mucoid discharge. Colonic mitochondrial oxygen consumption was not impacted by treatment (P >0.10). Further, ATTD of DM, OM, N, and GE were reduced in DDGS pigs compared with CON pigs (P< 0.001), whilst nutrient digestibility was not reduced in RS pigs. Taken together, these data show Bhyo does not appear to reduce ex vivo colonic integrity. Further, the RS diet may reduce severity of a Bhyo challenge.

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