scholarly journals Connective tissue biomatrix: its isolation and utilization for long-term cultures of normal rat hepatocytes.

1980 ◽  
Vol 87 (1) ◽  
pp. 255-263 ◽  
Author(s):  
M Rojkind ◽  
Z Gatmaitan ◽  
S Mackensen ◽  
M A Giambrone ◽  
P Ponce ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Connective Tissue ◽  
Basement Membrane ◽  
Rat Liver ◽  
Rat Hepatocytes ◽  
Ground Substance ◽  
Type I ◽  
Term Survival ◽  
Normal Rat

A new procedure is introduced for the isolation of connective tissue fibers, called biomatrix, containing a significant portion of the extracellular matrix (basement membrane components and components of the ground substance). Biomatrix isolated from normal rat liver contains >90% of the tissue's collagens and all of the known collagen types, including types I and III and basement membrane collagens. The purified collagenous fibers are associated with noncollagenous acidic proteins (including fibronectins and possibly small amounts of glycosaminoglycans). Procedures are also described for preparing tissue culture substrates with these fibers by either smearing tissue culture dishes with frozen sections or by shredding the biomatrix into small fibrils with a homogenizer. The biomatrix as a substrate has a remarkable ability to sustain normal rat hepatocytes long-term in culture. The hepatocytes, which on tissue culture plastic or on type I collagen gels do not survive more than a few weeks, have been maintained for more than 5 mo in vitro when cultured on biomatrix. These cells cultured on rat liver biomatrix show increased attachment and survival efficiencies, long-term survival (months) and retention of some hepatocyte-specific functions.

scholarly journals Tolerance and pancreatic islet transplantation

2001 ◽  
Vol 356 (1409) ◽  
pp. 759-765 ◽  
Author(s):  
Luca Inverardi ◽  
Camillo Ricordi
Keyword(s):  
Diabetes Mellitus ◽  
Islet Transplantation ◽  
Type I Diabetes ◽  
Immunological Tolerance ◽  
Type I Diabetes Mellitus ◽  
Current Status ◽  
Type I ◽  
Pancreatic Islet Transplantation ◽  
Term Survival

Islet transplantation holds renewed promise as a cure for type I diabetes mellitus. Results of recent clinical trials have shown remarkable success, and have reignited universal optimism for this procedure. In spite of this success, the need for life–long immunosuppression of the recipient still limits islet transplantation to patients with poorly controlled diabetes or to those requiring kidney transplantation. It is obvious that the achievement of immunological tolerance would broaden the indication for islet transplantation to a much larger cohort of patients with type I diabetes mellitus, most likely preventing long–term complications and contributing to a much improved quality of life. Increased understanding of the basic mechanisms of tolerance induction has resulted in the implementation of numerous experimental approaches to achieve long–term survival of islet grafts in the absence of chronic immunosuppression. In this brief review we will attempt to summarize the current status of research and knowledge.

EXTH-77. POLIO VIROTHERAPY OF MURINE BRAIN TUMORS INDUCES MICROGLIA PROLIFERATION AND INFLAMMATION THAT IS POTENTIATED BY IMMUNE CHECKPOINT BLOCKADE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi181-vi181
Author(s):  
Yuanfan Yang ◽  
Michael Brown ◽  
Kevin Stevenson ◽  
Giselle lopez ◽  
Reb Kornahrens ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Checkpoint ◽  
Response Rate ◽  
Cd8 T Cell ◽  
Gene Set Enrichment Analysis ◽  
Type I ◽  
Acute Type ◽  
Type I Ifn ◽  
Term Survival

Abstract Immunotherapy with polio:rhinovirus recombinant (PVSRIPO) has shown evidence of efficacy in a phase I clinical trial for recurrent GBM, resulting in durable radiographic responses and 21% long-term survival at 36 months. Ongoing research aims to enhance the clinical response rate by resolving the mechanisms of action and therapy resistance in vivo, thereby devising more effective therapies. Mouse glioma (CT2A) cells were intracranially implanted (day 0) in transgenic mice carrying poliovirus receptor CD155, and treated with intratumor PVSRIPO (5×105 pfu; day 6) to dissect early and late events following therapy. A blinded pathological review of 45 post-treatment tumors was performed. On day 8, a histological response, featured by tumor dissociation and shrinkage, with inflammation and microglia enrichment in the treated hemisphere, was common in PVSRIPO group (6/7) compared to controls (0/4). However, the response rate fell over time (7/12 on day 12; 1/7 on day 15) and the therapy was overcome by aggressive tumor regrowth. RNAseq was performed and Gene Set Enrichment Analysis of the tumor microenvironment revealed an acute type-I interferon (IFN)-related inflammation, correlating with the histological findings of profound proinflammatory engagement of microglia (Iba1+) widespread in the treated hemisphere. Microglia proliferation (Ki67+) was observed in the treated hemisphere, likely resulting from PVSRIPO infection, in CT2A and B16 intracranial models. This suggests an association of adaptive antitumor immunity—elicited by immediate intratumor type-I IFN-dominant inflammation—with tumor regression. Thus, buttressing type-I IFN directed antitumor CD8+T cell immunity, e.g. with blockade of the PD1:PD-L1 immune checkpoint, might contribute to tumor remission. Indeed, combination therapy with αPD-L1 antibody in the CT2A model showed longer median survival and higher long-term remission rate compared to monotherapy alone; CD8 T cell depletion can completely abrogate this efficacy with this therapy combination, confirming the role of anti-tumor immunity in this approach.

Long-Term Survival on Renal Replacement Therapy for Primary Hyperoxaluria Type I

Nephron ◽  
1993 ◽  
Vol 63 (2) ◽  
pp. 217-221 ◽  
Author(s):  
P. Calzavara ◽  
M. Marangelld ◽  
M. Petrarulo ◽  
P. Ballanti ◽  
E. Bonucci ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Primary Hyperoxaluria ◽  
Type I ◽  
Term Survival ◽  
Primary Hyperoxaluria Type ◽  
Hyperoxaluria Type I ◽  
Primary Hyperoxaluria Type I ◽  
Hyperoxaluria Type

Cyclophosphamide induces type I interferon and augments the number of CD44hi T lymphocytes in mice: implications for strategies of chemoimmunotherapy of cancer

Blood ◽  
2000 ◽  
Vol 95 (6) ◽  
pp. 2024-2030 ◽  
Author(s):  
Giovanna Schiavoni ◽  
Fabrizio Mattei ◽  
Tiziana Di Pucchio ◽  
Stefano M. Santini ◽  
Laura Bracci ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Adoptive Immunotherapy ◽  
Messenger Rna ◽  
Type I ◽  
Type I Ifn ◽  
Term Survival ◽  
Spleen Lymphocytes

Abstract In a previous study, we reported that a single injection of cyclophosphamide (CTX) in tumor-bearing mice resulted in tumor eradication when the animals were subsequently injected with tumor-sensitized lymphocytes. Notably, CTX acted by inducing bystander effects on T cells, and the response to the combined CTX/adoptive immunotherapy regimen was inhibited in mice treated with antibodies to mouse interferon (IFN)–/β. In the present study, we have investigated whether CTX induced the expression of type I IFN, and we have characterized the CTX effects on the phenotype of T cells in normal mice. CTX injection resulted in an accumulation of type I IFN messenger RNA in the spleen of inoculated mice, at 24 to 48 hours, that was associated with IFN detection in the majority of the animals. CTX also enhanced the expression of the Ly-6C on spleen lymphocytes. This enhancement was inhibited in mice treated with anti–type I IFN antibodies. Moreover, CTX induced a long-lasting increase in in vivo lymphocyte proliferation and in the percentage of CD44hiCD4+ and CD44hiCD8+T lymphocytes. These results demonstrate that CTX is an inducer of type I IFN in vivo and enhances the number of T cells exhibiting the CD44hi memory phenotype. Since type I IFN has been recently recognized as the important cytokine for the in vivo expansion and long-term survival of memory T cells, we suggest that induction of this cytokine may explain at least part of the immunomodulatory effects observed after CTX treatment. Finally, these findings provide a new rationale for combined treatments with CTX and adoptive immunotherapy in cancer patients.

P1182Asymptomatic masses on the pacing leads - influence on long term survival

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
A Polewczyk ◽  
D Nowosielecka ◽  
A Tomaszewski ◽  
W Brzozowski ◽  
D Szczesniak-Stanczyk ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Clinical Significance ◽  
Electronic Devices ◽  
Single Center ◽  
Term Survival ◽  
Long Term Survival ◽  
Cardiac Implantable Electronic Devices ◽  
Pacing Leads

Abstract Background Asymptomatic Masses on Endocardiac Leads  (AMELs) are relatively often found in echocardiography in patients with cardiac implantable electronic devices (CIED) but their clinical significance is unknown. Purpose Aim of the study was to evaluate the incidence of AMELs and assesment of their influence on long term survival (mean follow up- 4,28 ± 3,13 years) of patients undergoing transvenous leads extraction (TLE). Methods We analyzed the clinical data of patients undergoing TLE in single center in years 2006-2019. Echocardiography before TLE was performed in 2558  patients (60,4% male). AMELs were detected in 426 (16,7%) cases. Classifications of AMELs included connective tissue surronding the leads, clots, alike vegetations masses.  Additionally, real vegetations, thickening of the leads and strong connective tissue scars were distinguished. Long term survival was compared between individual types of AMELs and patients without any additional masses on the leads. Results are presented in the table. Conclusion Poor long-term survival was observed in patients with AMELs on the pacing leads. Abstract Table

Allogeneic Hepatocyte Transplantation Using FK 506

1997 ◽  
Vol 6 (1) ◽  
pp. 77-83 ◽  
Author(s):  
P.M. Markus ◽  
P. Krause ◽  
A. Fayyazi ◽  
K. Honnicke ◽  
H. Becker
Keyword(s):  
Rat Hepatocytes ◽  
Allogeneic Transplantation ◽  
Hepatocyte Transplantation ◽  
Major Histocompatibility ◽  
Term Survival ◽  
Fk 506 ◽  
Relative Ease ◽  
Donor Type ◽  
Cytological Features

Hepatocyte transplantation is an intriguing alternative to orthotopic liver transplantation. While engraftment of syngeneic hepatocytes can be achieved with relative ease, engraftment of allogeneic hepatocytes has been far more complicated. We used FK 506 (Tacrolimus), a novel and highly efficient immunosuppressant, which has been reported to augment liver regeneration in rats. Recipients of isolated syngeneic (LEW) and allogeneic (Wistar F.) rat hepatocytes (major histocompatibility barrier) recieved different immunosuppressive regiments with FK 506 or Cyclosporine A (CsA). Mature syngeneic hepatocytes could be retrieved up to post op day 300 with the lowest number of hepatocytes on post op day 20. Following allogeneic transplantation, no mature hepatocytes could be identified after post op day 10, though ductular like structures within the spleen were found in FK 506 but not CsA-treated animals. The epithelial cells of ductular like structures exhibit cytological features of CK-19 positive cells. Our results suggest that under CsA or FK 506 immunosuppression long-term survival of mature allogeneic hepatocytes within the spleen cannot be achieved across a major histocompatibility barrier though FK 506 allows engraftment of allogeneic donor type ductular cells. Copyright © 1997 Elsevier Science Inc.

Insulin induction of c-Ki-ras in rat liver and in cultured normal rat hepatocytes

1993 ◽  
Vol 104 (2) ◽  
pp. 341-347
Author(s):  
Sai On Chan ◽  
Susanna Siu Chun Wong ◽  
Desmond Chak Yew Yeung
Keyword(s):  
Rat Liver ◽  
Rat Hepatocytes ◽  
Normal Rat
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