| 1. |
- Lin, Xue, et al.
(författare)
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Controlled release of matrix metalloproteinase 1 with or without skeletal myoblasts transplantation improves cardiac function of rat hearts with chronic myocardial infarction.
- 2009
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Ingår i: Tissue engineering. Part A. - : Mary Ann Liebert Inc. - 1937-335X .- 1937-3341. ; 15:9, s. 2699-706
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Tidskriftsartikel (refereegranskat)abstract
- Skeletal myoblast transplantation has been applied clinically for severe ischemic cardiomyopathy. Matrix metalloproteinase 1 (MMP-1) reduces fibrosis and prevents the progress of heart failure. We hypothesized that MMP-1 administration to the infarct area enhances the efficacy of skeletal myoblast transplantation. The controlled release of MMP-1 improved cardiac functions of rats with chronic myocardiac infarction with or without transplantation of skeletal myoblasts. Improvement in cardiac function and small fibrotic area inside the infarcted area were observed compared with those of myoblast transplantation. In conclusion, controlled release of MMP-1 was effective in cardioprotection in postmyocardial infarction although the combination with cell transplantation showed the similar effect.
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| 2. |
- Ma, Li-Ping, et al.
(författare)
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Interleukin-6-deficient mice resist development of experimental autoimmune cardiomyopathy induced by immunization of β1-adrenergic receptor.
- 2012
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 155:1, s. 20-25
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: IL-6 is known to be an important mediator in immune response and is now suggested to be involved in the pathogenesis of autoimmune diseases. However, little is known about the role of IL-6 in β(1)-adrenergic receptor induced autoimmune cardiomyopathy. MATERIALS AND METHODS: Twenty IL-6-deficient (IL-6(-/-)) mice and fifty-one wild type C57BL/6J (WT) mice were immunized with a synthetic peptide corresponding to the second extracellular loop of the β(1) (β(1)AR ECII) at 0, 1, 5, 9, 13weeks and observed until 25weeks. Another forty-one WT mice and twenty IL-6(-/-) mice were used as controls receiving vehicle in the same manner. RESULTS: As compared with IL-6(-/-) immunized and control mice, WT immunized mice showed increased end-systolic left ventricular dimension and end-diastolic left ventricular dimension as well as decreased fractional shortening and circumferential fiber shortening in the end of the experiment, which was accompanied by significantly increased antibody level. Moreover, mRNAs encoding for β(1)-adrenergic receptor kinase (GRK2), B-type natriuretic peptide (BNP) and β(1) adrenergic receptor (Adrb1) in heart tissues from WT immunized group were increased. There was a significant positive correlation among end-diastolic left ventricular dimension, autoantibody titer and mRNA expressions of BNP, Adrb1and GRK2. CONCLUSION: Our results demonstrated that immunization with β1AR ECII was unable to induce an early stage phenotype of cardiomyopathy in IL-6(-/-) mice, being different from wild type in which cardiomyopathy was observed, suggesting that IL-6 plays a key role in the regulation of β(1)AR induced autoimmune cardiomyopathy possibly through its enhanced antibody production.
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| 3. |
- Nayakawde, Nikhil, et al.
(författare)
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Combined Use of Detergents and Ultrasonication for Generation of an Acellular Pig Larynx
- 2021
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Ingår i: Tissue Engineering Part A. - : Mary Ann Liebert Inc. - 1937-3341 .- 1937-335X. ; 27:5-6, s. 362-371
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Tidskriftsartikel (refereegranskat)abstract
- The larynx is a fairly complex organ comprised of different muscles, cartilages, mucosal membrane, and nerves. Larynx cancer is generally the most common type of head and neck cancer. Treatment options are limited in patients with total or partial laryngectomy. Tissue-engineered organs have shown to be a promising alternative treatment for patients with laryngectomy. In this report we present an alternative and simple procedure to construct a whole pig larynx scaffold consisting of complete acellular structures of integrated muscle and cartilage. Larynges were decellularized (DC) using perfusion-agitation with detergents coupled with ultrasonication. DC larynges were then characterized to investigate the extracellular matrix (ECM) proteins, residual DNA, angiogenic growth factors, and morphological and ultrastructural changes to ECM fibers. After 17 decellularization cycles, no cells were observed in all areas of the larynx as confirmed by hematoxylin and eosin and DAPI (4 ',6-diamidino-2-phenylindole) staining. However, DC structures of dense thyroid and cricoid cartilage showed remnants of cells. All structures of DC larynges (epiglottis [p < 0.0001], muscle [p < 0.0001], trachea [p = 0.0045], and esophagus [p = 0.0008]) showed DNA <50 ng/mg compared with native larynx. Immunohistochemistry, Masson's trichrome staining, and Luminex analyses showed preservation of important ECM proteins and angiogenic growth factors in DC larynges. Compared with other growth factors, mostly retained growth factors in DC epiglottis, thyroid muscle, and trachea include granulocyte colony-stimulating factor, Leptin, fibroblast growth factor-1, Follistatin, hepatocyte growth factor, and vascular endothelial growth factor-A. Scanning electron microscopy and transmission electron microscopy analysis confirmed the structural arrangements of ECM fibers in larynges to be well preserved after DC. Our findings suggest that larynges can be effectively DC using detergent ultrasonication. ECM proteins and angiogenic growth factors appear to be better preserved using this method when compared with the native structures of larynges. This alternative DC method could be helpful in building scaffolds from dense tissue structures such as cartilage, tendon, larynx, or trachea for futurein vitrorecellularization studies orin vivoimplantation studies in the clinic. Impact statement This study successfully created decellularized porcine larynx using novel method of perfusion-agitation with detergents and ultrasonication, which maintained three-dimensional architecture of the larynx scaffold. Our method is devoid of harmful enzymes, which may prevent cellular repopulation or induce inflammatory response uponin vivoimplantation. We studied important aspect of preservation of extracellular matrix proteins in different structures of the larynx. Hence, our decellularization method could be used as an alternative method to decellularize various dense tissues such as cartilage or tendon.
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| 4. |
- Nayakawde, Nikhil, et al.
(författare)
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In Vitro Regeneration of Decellularized Pig Esophagus Using Human Amniotic Stem Cells
- 2020
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Ingår i: Bioresearch Open Access. - : Mary Ann Liebert Inc. - 2164-7860. ; 9:1, s. 22-36
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Tidskriftsartikel (refereegranskat)abstract
- Decellularization of esophagus was studied using three different protocols. The sodium deoxycholate/DNase-I (SDC/DNase-I) method was the most successful as evidenced by histology and DNA quantification of the acellular scaffolds. Acellular scaffolds were further analyzed and compared with native tissue by histology, quantitative analysis of DNA, and extracellular matrix (ECM) proteins. Histologically, the SDC/DNase-I protocol effectively produced scaffold with preserved structural architecture similar to native tissue architecture devoid of any cell nucleus. ECM proteins, such as collagen, elastin, and glycosaminoglycans were present even after detergent-enzymatic decellularization. Immunohistochemical analysis of acellular scaffold showed weak expression of Gal 1, 3 Gal epitope compared with native tissue. For performing recellularization, human amnion-derived mesenchymal stem cells (MSCs) and epithelial cells were seeded onto acellular esophagus in a perfusion-rotation bioreactor. In recellularized esophagus, immunohistochemistry showed infiltration of MSCs from adventitia into the muscularis externa and differentiation of MSCs into the smooth muscle actin and few endothelial cells (CD31). Our study demonstrates successful preparation and characterization of a decellularized esophagus with reduced load of Gal 1, 3 Gal epitope with preserved architecture and ECM proteins similar to native tissue. Upon subsequent recellularization, xenogeneic acellular esophagus also supported stem cell growth and partial differentiation of stem cells. Hence, the current study offers the hope for preparing a tissue-engineered esophagus in vitro which can be transplanted further into pigs for further in vivo evaluation.
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| 5. |
- Olausson, Michael, 1956, et al.
(författare)
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Long-term Transplant Function After Thrombolytic Treatment Ex Vivo of Donated Kidneys Retrieved 4 to 5 H After Circulatory Death
- 2022
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 106:12, s. 2348-2359
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Tidskriftsartikel (refereegranskat)abstract
- Background. Using a novel thrombolytic technique, we present long-term transplant function, measured by creatinine and iohexol clearance, after utilizing kidneys from porcine donors with uncontrolled donation after circulatory deaths, with 4.5-5 h of warm ischemia. Methods. Pigs in the study group were subjected to simulated circulatory death. After 2 h, ice slush was inserted into the abdomen and 4.5 h after death, the kidneys were retrieved. Lys-plasminogen, antithrombin-III, and alteplase were injected through the renal arteries on the back table. Subsequent ex vivo perfusion was continued for 3 h at 15 degrees C, followed by 3 h with red blood cells at 32 degrees C, and then transplanted into pigs as an autologous graft as only renal support. Living-donor recipient pigs that did not receive ex vivo perfusion, and unilateral nephrectomized pigs served as the controls. Results. Pigs in the study group (n = 13), surviving 10 d or more were included, of which 7 survived for 3 mo. Four animals in the living-donor group (n = 6) and all 5 nephrectomized animals survived for 3 mo. Creatinine levels in the plasma and urine, neutrophil gelatinaseassociated lipocalin levels, Kidney Injury Marker-1 expression, and iohexol clearance at 3 mo did not differ significantly between the study and living-donor groups. Histology and transmission electron microscopy after 3 mo showed negligible fibrosis and no other damage. Conclusions. The present method salvages kidneys from extended unontrolled donation after circulatory death using thrombolytic treatment while preserving histology and enabling transplantation after ex vivo reconditioning, with clinically acceptable late function after 3 mo, as measured by creatinine and iohexol clearance.
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| 6. |
- Olausson, Michael, et al.
(författare)
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Long-term Transplant Function After Thrombolytic Treatment Ex Vivo of Donated Kidneys Retrieved 4 to 5 Hours After Circulatory Death
- 2022
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Ingår i: Transplantation. - 0041-1337. ; 106:12, s. 2348-2359
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Tidskriftsartikel (refereegranskat)abstract
- Background. Using a novel thrombolytic technique, we present long-term transplant function, measured by creatinine and iohexol clearance, after utilizing kidneys from porcine donors with uncontrolled donation after circulatory deaths, with 4.5–5 h of warm ischemia. Methods. Pigs in the study group were subjected to simulated circulatory death. After 2 h, ice slush was inserted into the abdomen and 4.5 h after death, the kidneys were retrieved. Lys-plasminogen, antithrombin-III, and alteplase were injected through the renal arteries on the back table. Subsequent ex vivo perfusion was continued for 3 h at 15°C, followed by 3 h with red blood cells at 32°C, and then transplanted into pigs as an autologous graft as only renal support. Living-donor recipient pigs that did not receive ex vivo perfusion, and unilateral nephrectomized pigs served as the controls. Results. Pigs in the study group (n = 13), surviving 10 d or more were included, of which 7 survived for 3 mo. Four animals in the living-donor group (n = 6) and all 5 nephrectomized animals survived for 3 mo. Creatinine levels in the plasma and urine, neutrophil gelatinase-associated lipocalin levels, Kidney Injury Marker-1 expression, and iohexol clearance at 3 mo did not differ significantly between the study and living-donor groups. Histology and transmission electron microscopy after 3 mo showed negligible fibrosis and no other damage. Conclusions. The present method salvages kidneys from extended unontrolled donation after circulatory death using thrombolytic treatment while preserving histology and enabling transplantation after ex vivo reconditioning, with clinically acceptable late function after 3 mo, as measured by creatinine and iohexol clearance.
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| 7. |
- Olausson, Michael, 1956, et al.
(författare)
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Novel Ex-Vivo Thrombolytic Reconditioning of Kidneys Retrieved 4 to 5 Hours After Circulatory Death
- 2022
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 106:8, s. 1577-1588
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Tidskriftsartikel (refereegranskat)abstract
- Background. Due to organ shortage, many patients do not receive donor organs. The present novel thrombolytic technique utilizes organs from donors with uncontrolled donation after circulatory deaths (uDCD), with up to 4-5h warm ischemia, without advanced cardiopulmonary resuscitation (aCPR) or extracorporeal circulation (EC) after death. Methods. The study group of pigs (n = 21) underwent simulated circulatory death. After 2h, an ice slush was inserted into the abdomen. Kidneys were retrieved 4.5h after death. Lys-plasminogen, antithrombin-III (ATIII), and alteplase (tPA) were injected through the renal arteries on the back table. Subsequent ex vivo perfusion at 15 degrees C was continued for 3h, followed by 3h with red blood cells (RBCs) at 32 degrees C. Perfusion outcome and histology were compared between uDCD kidneys, receiving no thrombolytic treatment (n = 8), and live donor kidneys (n = 7). The study kidneys were then transplanted into pigs as autologous grafts with a single functioning autologous kidney as the only renal support. uDCD control pigs (n = 8), receiving no ex vivo perfusion, served as controls. Results. Vascular resistance decreased to <200 mmHg/mL/min (P < 0.0023) and arterial flow increased to >100mL/100g/min (P < 0.00019) compared to controls. In total 13/21 study pigs survived for >10 days, while all uDCD control pigs died. Histology was preserved after reconditioning, and the creatinine level after 10 days was next to normal. Conclusions. Kidneys from extended uDCD, not receiving aCPR/EC, can be salvaged using thrombolytic treatment to remove fibrin thrombi while preserving histology and enabling transplantation with a clinically acceptable early function.
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| 8. |
- Premaratne, Goditha U, et al.
(författare)
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Stromal Vascular Fraction Transplantation as an Alternative Therapy for Ischemic Heart Failure: Anti-inflammatory Role.
- 2011
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Ingår i: Journal of cardiothoracic surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Background The aims of this study were: (1) to show the feasibility of using adipose-derived stromal vascular fraction (SVF) as an alternative to bone marrow mono nuclear cell (BM-MNC) for cell transplantation into chronic ischemic myocardium; and (2) to explore underlying mechanisms with focus on anti-inflammation role of engrafted SVF and BM-MNC post chronic myocardial infarction (MI) against left ventricular (LV) remodelling and cardiac dysfunction. Methods Four weeks after left ante rior descending coronary artery ligation, 32 Male Lewis rats with moderate MI were divided into 3 groups. SVF group (n = 12) had SVF cell transplantation (6 × 106 cells). BM-MNC group (n = 12) received BM-MNCs (6 × 106) and the control (n = 10) had culture medium. At 4 weeks, after the final echocardiography, histological sections were stained with Styrus red and immunohistochemical staining was performed for α-smooth muscle actin, von Willebrand factor, CD3, CD8 and CD20. Results At 4 weeks, in SVF and BM-MNC groups, LV diastolic dimension and LV systolic dimension were smaller and fractional shortening was increased in echocardiography, compared to control group. Histology revealed highest vascular density, CD3+ and CD20+ cells in SVF transplanted group. SVF transplantation decreased myocardial mRNA expression of inflammatory cytokines TNF-α, IL-6, MMP-1, TIMP-1 and inhibited collagen deposition. Conclusions Transplantation of adipose derived SVF cells might be a useful therapeutic option for angiogenesis in chronic ischemic heart disease. Anti-inflammation role for SVF and BM transplantation might partly benefit for the cardioprotective effect for chronic ischemic myocardium.
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