RECELLULARIZATION OF XENOGRAFT HEART VALVES REDUCES THE XENOREACTIVE IMMUNE RESPONSE IN AN IN-VIVO RAT MODEL

2020 ◽  
Vol 36 (10) ◽  
pp. S103
Author(s):  
S. Bozso ◽  
R. EL-Andari ◽  
L. Zhu ◽  
B. Adam ◽  
M. Moon ◽  
...  
Keyword(s):  
Immune Response ◽  
Rat Model ◽  
Heart Valves

scholarly journals Recellularization of Xenograft Heart Valves Reduces the Xenoreactive Immune Response in an In-Vivo Rat Model

2021 ◽  
Vol 40 (4) ◽  
pp. S299
Author(s):  
S.J. Bozso ◽  
R. EL-Andari ◽  
L. Zhu ◽  
B. Adam ◽  
M.C. Moon ◽  
...  
Keyword(s):  
Immune Response ◽  
Rat Model ◽  
Heart Valves

Abstract 226: Recellularization of Xenograft Heart Valves Reduces the Xenoreactive Immune Response in an In Vivo Rat Model

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Sabin J Bozso ◽  
Ryaan EL-Andari ◽  
Lin Fu Zhu ◽  
Benjamin Adam ◽  
Michael C Moon ◽  
...  
Keyword(s):  
Immune Response ◽  
Aortic Valve ◽  
Guinea Pig ◽  
Rat Model ◽  
Serum Immunoglobulin ◽  
Total Serum ◽  
Sprague Dawley ◽  
Cellular Infiltrate ◽  
Immunoglobulin Production

Background: Current xenograft valve constructs provoke an intense immune response that may lead to valve dysfunction. Our aim was to address the role of autologous mesenchymal stem cell (MSC) recellularization of xenogenic valves on the activation of the xenoreactive immune response in an in-vivo rat model. Methods: Explanted aortic valve constructs from female Hartley guinea pigs were procured and decellularized, followed by recellularization with syngeneic Sprague-Dawley rat MSCs. The recellularized aortic valve xenografts were then implanted into the infrarenal aorta of recipient female Sprague-Dawley rats. Grafts were implanted as either syngeneic grafts, non-decellularized (fresh), decellularized and recellularized xenografts. Rats were euthanized after 7-days, exsanguinated and the grafts explanted. Total serum immunoglobulin was quantified and histological analysis perfomed to analyze the immune response. Results: Overall survival to endpoint was significantly lower in the decellularized xenograft group (67%; 4/6), compared to fresh (100%; 6/6) and recellularized grafts (100%; 6/6). Similarly grafts in the decellularized group were more likely to have completely thrombosed (50%; 2/4), compared to fresh (33%; 2/6) and recellularized grafts (0%; 0/6). Decellularized guinea pig xenografts, when implanted into rats in-vivo , result in significantly reduced total serum immunoglobulin production and significantly reduced graft cellular infiltrate when compared to fresh xenografts. Moreover, when decellularized guinea pig xenografts were recellularized with syngeneic rat MSCs there was an additional decrease in total serum immunoglobulin production and graft cellular infiltrate when compared to both fresh and decellularized xenografts. Importantly, recellularized guinea pig xenografts had an equivalent total immunoglobulin production and graft cellular infiltrate when compared to syngeneic rat aortic valve controls. Conclusions: Autologous MSC recellularization of xenogenic valves reduces the xenoreactive immune response in an in-vivo rat model and may be an effective approach to decrease the progression of xenograft valve dysfunction.

Recellularization of xenograft heart valves reduces the xenoreactive immune response in an in vivo rat model

2021 ◽  
Author(s):  
Sabin J Bozso ◽  
Jimmy J H Kang ◽  
Ryaan EL-Andari ◽  
Nicholas Fialka ◽  
Lin Fu Zhu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Stem Cell ◽  
Aortic Valve ◽  
Mesenchymal Stem Cell ◽  
Rat Model ◽  
Cell Infiltration ◽  
Immunoglobulin Production ◽  
Autologous Grafts

Abstract OBJECTIVES Our aim was to address the role of autologous mesenchymal stem cell recellularization of xenogenic valves on the activation of the xenoreactive immune response in an in vivo rat model. METHODS Explanted aortic valve constructs from female Hartley guinea pigs were procured and decellularized, followed by recellularization with autologous Sprague-Dawley rat mesenchymal stem cells. Aortic valve xenografts were then implanted into the infrarenal aorta of recipient rats. Grafts were implanted as either autologous grafts, non-decellularized (NGP), decellularized and recellularized xenografts (RGP). Rats were euthanized after 7 and 21 days and exsanguinated and the grafts were explanted. RESULTS The NGP grafts demonstrated significant burden of granulocytes (14.3 cells/HPF) and CD3+ T cells (3.9 cells/HPF) compared to the autologous grafts (2.1 granulocytes/HPF and 0.72 CD3+ T cells/HPF) after 7 days. A lower absolute number of infiltrating granulocytes (NGP vs autologous, 6.4 vs 2.4 cells/HPF) and CD3+ T cells (NGP vs autologous, 2.8 vs 0.8 cells/HPF) was seen after 21 days. Equivalent granulocyte cell infiltration in the RGP grafts (2.4 cells/HPF) compared to the autologous grafts (2.1 cells/HPF) after 7 and 21 days (2.8 vs 2.4 cells/HPF) was observed. Equivalent CD3+ T-cell infiltration in the RGP grafts (0.63 cells/HPF) compared to the autologous grafts (0.72 cells/HPF) after 7 and 21 days (0.7 vs 0.8 cells/HPF) was observed. Immunoglobulin production was significantly greater in the NGP grafts compared to the autologous grafts at 7 (123.3 vs 52.7 mg/mL) and 21 days (93.3 vs 71.6 mg/mL), with a similar decreasing trend in absolute production. Equivalent immunoglobulin production was observed in the RGP grafts compared to the autologous grafts at 7 (40.8 vs 52.7 mg/mL) and 21 days (29.5 vs 71.6 mg/mL). CONCLUSIONS Autologous mesenchymal stem cell recellularization of xenogenic valves reduces the xenoreactive immune response in an in vivo rat model and may be an effective approach to decrease the progression of xenograft valve dysfunction.

In vivo multimodal (MRI, SPECT) imaging of the 6-OHDA rat model for Parkinson's disease correlated with behavior and histology

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S392-S392
Author(s):  
Nadja Van Camp ◽  
Koen Van Laere ◽  
Ruth Vreys ◽  
Marleen Verhoye ◽  
Erwin Lauwers ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Spect Imaging ◽  
Multimodal Mri

In vivo repopulation of tissue engineered heart valves

2010 ◽  
Vol 58 (S 01) ◽  
Author(s):  
PM Dohmen ◽  
A Lembcke ◽  
S Holinski ◽  
JP Braun ◽  
W Konertz
Keyword(s):  
Heart Valves ◽  
Tissue Engineered Heart Valves

One Year In-Vivo Functionality of Transvenously Implanted Tissue-Engineered Pulmonary Heart Valves in Sheep

2016 ◽  
Vol 64 (S 02) ◽  
Author(s):  
H. Spriestersbach ◽  
L. Bruder ◽  
B. Sanders ◽  
E. Fioretta ◽  
D. O h-Icí ◽  
...  
Keyword(s):  
Heart Valves ◽  
One Year

The Glycosaminoglycan of Recombinant Human Soluble Thrombomodulin Affects Antithrombotic Activity in a Rat Model of Tissue Factor-Induced Disseminated Intravascular Coagulation

1992 ◽  
Vol 67 (03) ◽  
pp. 366-370 ◽  
Author(s):  
Katsuhiko Nawa ◽  
Teru Itani ◽  
Mayumi Ono ◽  
Katsu-ichi Sakano ◽  
Yasumasa Marumoto ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Disseminated Intravascular Coagulation ◽  
Rat Model ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Soluble Thrombomodulin ◽  
Intravascular Coagulation ◽  
Platelet Counts ◽  
Recombinant Human Soluble Thrombomodulin

SummaryPrevious studies on recombinant human soluble thrombomodulin (rsTM) from Chinese hamster ovary cells revealed that rsTM was expressed as two proteins that differed functionally in vitro due to the presence (rsTMp) or absence (rsTMa) of chondroitin-4-sulfate. The current study evaluates the in vivo behavior of rsTM in rats and in a rat model of tissue factor-induced disseminated intravascular coagulation (DIC). rsTMp was more potent than rsTMa for prolongation of the activated partial thromboplastin time (APTT) and their in vivo half-lives determined by ELISA were 20 min for rsTMp and 5.0 h for rsTMa. Injection of a tissue factor suspension (5 mg/kg) resulted in DIC as judged by decreased platelet counts and fibrinogen concentrations, prolonged APTT, and increased fibrin and fibrinogen degradation products (FDP) levels. A bolus injection of either rsTM (0.2 mg/kg) 1 min before induction of DIC essentially neutralized effects on platelets, fibrinogen, and FDP levels, and had only a moderate effect on APTT prolongation. The dose of anticoagulant to inhibit the drop in platelet counts by 50% (ED50) was 0.2 mg/kg rsTMa, 0.07 mg/kg rsTMp, and 7 U/ kg heparin. The effect of increasing concentrations of rsTM and heparin on bleeding times were compared in experiments involving incision of the rat tail. Doubling of the bleeding times occurred at 5 mg/kg rsTMa, 3 mg/kg rsTMp or 90 U/kg heparin. These values represent a 25-fold increase over the ED50 for rsTMa, 43-fold for rsTMp and 13-fold for heparin. These results suggest that rsTMp is a potent anticoagulant to inhibit the platelet reduction when injected prior to the induction of DIC in rats.

The angiogenic factor CCN1 promotes re-endothelialization of decellularized pulmonary heart valves in vivo

2008 ◽  
Vol 56 (S 1) ◽  
Author(s):  
A Hilfiker ◽  
M Suprunov ◽  
D Hilfiker-Kleiner ◽  
I Tudorache ◽  
S Cebotari ◽  
...  
Keyword(s):  
Heart Valves ◽  
Angiogenic Factor
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