Pancreatitis is a disease characterized by an acute or chronic inflammatory process of the pancreas, induced by the activation of trypsin inside acinocytes. These processes result in necrosis of the organ's parenchyma, abscess formation, and systemic complications, contributing to patient mortality rates ranging from 30-47%. As of now, there is no globally recognized effective treatment for acute pancreatitis. Multipotent mesenchymal stem cells (MMSCs) are potential candidates for treating this disease due to their immunomodulatory properties. The aim of this study was to compare the therapeutic effects of transplanting native human umbilical cord-derived MMSCs (hUC-MMSCs) with hUC-MMSCs preconditioned with H2O2 in a rat model of acute pancreatitis. Materials and methods. Acute pancreatitis in rats was induced by intraperitoneal injection of L-arginine at a dose of 3.5 g/kg body weight at an interval of 1 hour. The rats were then categorized into four groups. Group 1 – negative control, where animals received a physiological solution; group 2 – positive control (pancreatitis). Three days after the onset of signs of developed acute pancreatitis, group 3 rats were intraperitoneally transplanted with native hUC-MMSCs, meeting the minimum criteria of the International Society for Cell and Gene Therapy, at a dose of 1.5×106 cells/kg. Group 4 received the same dose of hUC-MMSCs, but these cells were preconditioned with H2O2 at a concentration of 30 µM for 18 hours. The effects of both native and preconditioned hUC-MMSCs were evaluated at 3, 7, and 14 days after their introduction. Assessment criteria included the α-amylase index, identification of insulin in the islets of Langerhans, and histological analysis. Results. It was demonstrated that, three days post L-arginine administration, the α-amylase level surged by five times compared to the negative control, and blood glucose levels increased by 2.5 times, indicating damage to both the exocrine and endocrine parts of the pancreas. Microscopic examination revealed a 3.5-fold increase in fibrosis of the pancreatic parenchyma compared to the negative control. Three days after the transplantation of native hUC-MMSCs, the α-amylase level in the blood decreased by 1.7 times, and in the variant with preconditioned hUC-MMSCs, it decreased by 2 times compared to Group 2. By day 7, the α-amylase index in the native hUC-MMSCs group decreased by 2.4 times compared to the positive control, and in the preconditioned hUC-MMSCs group, it approached normal levels. A gradual recovery of the pancreatic architecture was observed by day 7, with a faster recovery in the preconditioned MMSCs group. Histological sections revealed a replacement of nuclei-free areas with acinocytes, indicated by a 3-fold decrease in the number of nuclei-free cells in the native hUC-MMSCs transplantation, and almost normal levels in the preconditioned hUC-MMSCs group. Both variants exhibited a positive histochemical PAS-reaction for the identi
{"title":"Comparison of the therapeutic effect of native and preconditioned human umbilical cord-derived multipotent mesenchymal stromal cells on a rat model of acute pancreatitis","authors":"Polina Pikus, Svitlana Rymar, Andriy Pustovalov, Nadiia Shuvalova, Ye Reshetnyk, Vitalii Kordium","doi":"10.22494/cot.v11i2.156","DOIUrl":"https://doi.org/10.22494/cot.v11i2.156","url":null,"abstract":"Pancreatitis is a disease characterized by an acute or chronic inflammatory process of the pancreas, induced by the activation of trypsin inside acinocytes. These processes result in necrosis of the organ's parenchyma, abscess formation, and systemic complications, contributing to patient mortality rates ranging from 30-47%. As of now, there is no globally recognized effective treatment for acute pancreatitis. Multipotent mesenchymal stem cells (MMSCs) are potential candidates for treating this disease due to their immunomodulatory properties. The aim of this study was to compare the therapeutic effects of transplanting native human umbilical cord-derived MMSCs (hUC-MMSCs) with hUC-MMSCs preconditioned with H2O2 in a rat model of acute pancreatitis. Materials and methods. Acute pancreatitis in rats was induced by intraperitoneal injection of L-arginine at a dose of 3.5 g/kg body weight at an interval of 1 hour. The rats were then categorized into four groups. Group 1 – negative control, where animals received a physiological solution; group 2 – positive control (pancreatitis). Three days after the onset of signs of developed acute pancreatitis, group 3 rats were intraperitoneally transplanted with native hUC-MMSCs, meeting the minimum criteria of the International Society for Cell and Gene Therapy, at a dose of 1.5×106 cells/kg. Group 4 received the same dose of hUC-MMSCs, but these cells were preconditioned with H2O2 at a concentration of 30 µM for 18 hours. The effects of both native and preconditioned hUC-MMSCs were evaluated at 3, 7, and 14 days after their introduction. Assessment criteria included the α-amylase index, identification of insulin in the islets of Langerhans, and histological analysis. Results. It was demonstrated that, three days post L-arginine administration, the α-amylase level surged by five times compared to the negative control, and blood glucose levels increased by 2.5 times, indicating damage to both the exocrine and endocrine parts of the pancreas. Microscopic examination revealed a 3.5-fold increase in fibrosis of the pancreatic parenchyma compared to the negative control. Three days after the transplantation of native hUC-MMSCs, the α-amylase level in the blood decreased by 1.7 times, and in the variant with preconditioned hUC-MMSCs, it decreased by 2 times compared to Group 2. By day 7, the α-amylase index in the native hUC-MMSCs group decreased by 2.4 times compared to the positive control, and in the preconditioned hUC-MMSCs group, it approached normal levels. A gradual recovery of the pancreatic architecture was observed by day 7, with a faster recovery in the preconditioned MMSCs group. Histological sections revealed a replacement of nuclei-free areas with acinocytes, indicated by a 3-fold decrease in the number of nuclei-free cells in the native hUC-MMSCs transplantation, and almost normal levels in the preconditioned hUC-MMSCs group. Both variants exhibited a positive histochemical PAS-reaction for the identi","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"41 12","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136228359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sergii Konovalov, Nina Konovalova, Vasyl Moroz, O. Deryabina, Olena Toporova, A. Tochylovsky, Vitaly Kordium
Neuroprotective therapy in acute cerebrovascular disorders is directly aimed at preserving neurons in the penumbra zone, but it also emphasizes the importance of gliogenesis in the affected area. Glial cells exhibit rapid reactivity and are highly sensitive to cerebral ischemic damage. Recent experimental studies have demonstrated the successful application of multipotent mesenchymal stromal cells (MMSCs) in stroke to modulate microglial activation. The aim of the study was to investigate the impact of MMSCs of different origins, MMSC lysate, and citicoline on glial components in a model of cerebral ischemia-reperfusion in rats. Materials and methods. The experiments were conducted on 190 male Wistar rats aged 4 months, weighing 160-190 g. After modeling cerebral ischemia-reperfusion through bilateral 20-minute occlusion of the internal carotid arteries, rats were intravenously administered MMSCs derived from human Wharton’s jelly, human adipose tissue, and rat Wharton’s jelly at a dose of 106 cells per animal. Other groups received fetal rat fibroblasts (106 cells/animal in 0.2 ml of physiological solution) and lysate from human Wharton’s jelly at a dose of 0.2 ml per animal. Control animals received 0.2 ml of physiological solution intravenously. The last group of rats received a single dose of the reference drug citicoline at a dose of 250 mg/kg. On the 7th and 14th days, the area and fluorescence intensity of cells expressing markers of astrocytes (GFAP), microglia (Iba1), and oligodendrocytes (Rip) were quantitatively assessed in CA1 hippocampal region slices using immunohistochemical examination and confocal microscopy. Results. On the 7th and 14th days after cerebral ischemia-reperfusion in rats, the intensity of fluorescence of GFAP-positive astrocytes and Iba1-positive microglial cells increased, indicating pronounced reactive astrogliosis and microglial activation in the CA1 region of the hippocampus. Meanwhile, ischemia-reperfusion had a significant impact on the content of Rip-positive oligodendrocytes in brain slices. The application of all treatments (transplantation of MMSCs of different origins, their lysate, or the reference drug citicoline) had a cytoprotective effect, reducing reactive astrogliosis and microgliosis both on the 7th and 14th days after injury. The best result was demonstrated with the treatment using MSCs from human Wharton’s jelly.s. Conclusion. Cerebral ischemia-reperfusion induces reactive gliosis through the activation of GFAP- and Iba1-positive glial cells in all layers of the hippocampus. The application of MSCs from human Wharton’s jelly and fetal rat fibroblasts significantly reduces its intensity on both the 7th and 14th days after injury modeling.
{"title":"Multipotent mesenchymal stromal cells of various origins reduce reactive gliosis in the hippocampal CA1 area during acute ischemia-reperfusion of the rat brain","authors":"Sergii Konovalov, Nina Konovalova, Vasyl Moroz, O. Deryabina, Olena Toporova, A. Tochylovsky, Vitaly Kordium","doi":"10.22494/cot.v11i2.159","DOIUrl":"https://doi.org/10.22494/cot.v11i2.159","url":null,"abstract":"Neuroprotective therapy in acute cerebrovascular disorders is directly aimed at preserving neurons in the penumbra zone, but it also emphasizes the importance of gliogenesis in the affected area. Glial cells exhibit rapid reactivity and are highly sensitive to cerebral ischemic damage. Recent experimental studies have demonstrated the successful application of multipotent mesenchymal stromal cells (MMSCs) in stroke to modulate microglial activation. The aim of the study was to investigate the impact of MMSCs of different origins, MMSC lysate, and citicoline on glial components in a model of cerebral ischemia-reperfusion in rats. Materials and methods. The experiments were conducted on 190 male Wistar rats aged 4 months, weighing 160-190 g. After modeling cerebral ischemia-reperfusion through bilateral 20-minute occlusion of the internal carotid arteries, rats were intravenously administered MMSCs derived from human Wharton’s jelly, human adipose tissue, and rat Wharton’s jelly at a dose of 106 cells per animal. Other groups received fetal rat fibroblasts (106 cells/animal in 0.2 ml of physiological solution) and lysate from human Wharton’s jelly at a dose of 0.2 ml per animal. Control animals received 0.2 ml of physiological solution intravenously. The last group of rats received a single dose of the reference drug citicoline at a dose of 250 mg/kg. On the 7th and 14th days, the area and fluorescence intensity of cells expressing markers of astrocytes (GFAP), microglia (Iba1), and oligodendrocytes (Rip) were quantitatively assessed in CA1 hippocampal region slices using immunohistochemical examination and confocal microscopy. Results. On the 7th and 14th days after cerebral ischemia-reperfusion in rats, the intensity of fluorescence of GFAP-positive astrocytes and Iba1-positive microglial cells increased, indicating pronounced reactive astrogliosis and microglial activation in the CA1 region of the hippocampus. Meanwhile, ischemia-reperfusion had a significant impact on the content of Rip-positive oligodendrocytes in brain slices. The application of all treatments (transplantation of MMSCs of different origins, their lysate, or the reference drug citicoline) had a cytoprotective effect, reducing reactive astrogliosis and microgliosis both on the 7th and 14th days after injury. The best result was demonstrated with the treatment using MSCs from human Wharton’s jelly.s. Conclusion. Cerebral ischemia-reperfusion induces reactive gliosis through the activation of GFAP- and Iba1-positive glial cells in all layers of the hippocampus. The application of MSCs from human Wharton’s jelly and fetal rat fibroblasts significantly reduces its intensity on both the 7th and 14th days after injury modeling.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139200637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-14DOI: 10.3390/transplantology4040020
Bibhuti Das, Justin Godown, Shriprasad R. Deshpande
Objectives: Limited data are available on renal dysfunction and neurologic complications in heart failure in children, when the heart failure is not related to congenital heart disease (CHD) or cardiac surgery. This study used a multi-center database to describe pediatric heart failure (pHF)-related renal dysfunction, neurological complications, and outcomes in non-CHD patients. Methods: The Pediatric Health Information System (PHIS) database between 2004 and 2020 was used to analyze the prevalence of renal dysfunction and neurologic complications associated with pHF hospitalizations and their impact on outcomes. Results: Of the 5515 hospitalizations included in the study, renal dysfunction was identified in 1239 (22.5%), and neurologic dysfunction was diagnosed in 539 (9.8%). The diagnosis of renal or neurologic complications was associated with significantly higher use of ICU therapies, including mechanical ventilation, parenteral nutrition, and mechanical circulatory support. Patients with significant renal dysfunction were likely to receive kidney transplants in 3.1% of the cases. Neurologic complications were higher in patients with pHF who underwent heart transplantation (21.3% vs. 7.8%, p < 0.001). Patients with renal dysfunction and neurologic complications had significantly higher mortality rates than those without renal dysfunction (11.7% vs. 4.3%, p < 0.001) and neurologic complications (18.4% vs. 4.6%, p < 0.001). Conclusions: Renal dysfunction and neurologic complications are common, resulting in significantly higher utilization of ICU therapies and mortality rates during non-CHD-related pHF hospitalization. Neurologic complications associated with hospitalization for pHF are associated with a significantly higher mortality, which has been underemphasized in the literature. This study assesses the burden of these morbidities and highlights the importance of monitoring and managing renal and neurologic complications in pHF to improve outcomes.
目的:当心力衰竭与先天性心脏病(CHD)或心脏手术无关时，儿童心力衰竭的肾功能障碍和神经系统并发症的数据有限。本研究使用一个多中心数据库来描述儿童心力衰竭(pHF)相关肾功能障碍、神经系统并发症和非冠心病患者的预后。方法:利用2004年至2020年儿童卫生信息系统(PHIS)数据库，分析与pHF住院相关的肾功能障碍和神经系统并发症的患病率及其对预后的影响。结果:在纳入研究的5515例住院患者中，1239例(22.5%)诊断为肾功能障碍，539例(9.8%)诊断为神经功能障碍。肾脏或神经系统并发症的诊断与ICU治疗的使用显著增加相关，包括机械通气、肠外营养和机械循环支持。有明显肾功能不全的患者可能接受肾移植的比例为3.1%。接受心脏移植的pHF患者神经系统并发症更高(21.3% vs. 7.8%， p <0.001)。肾功能不全合并神经系统并发症患者的死亡率明显高于无肾功能不全患者(11.7% vs. 4.3%， p <0.001)和神经并发症(18.4% vs. 4.6%， p <0.001)。结论:肾功能障碍和神经系统并发症是常见的，导致非冠心病相关性pHF住院期间ICU治疗的使用率和死亡率显著增加。与pHF住院相关的神经系统并发症与死亡率显著升高相关，这一点在文献中没有得到充分强调。本研究评估了这些疾病的负担，并强调了监测和管理pHF中肾脏和神经系统并发症以改善预后的重要性。
{"title":"Burden of Renal Dysfunction and Neurologic Complications in Hospitalized Pediatric Heart Failure Unrelated to Congenital Heart Disease: A Multicenter Study","authors":"Bibhuti Das, Justin Godown, Shriprasad R. Deshpande","doi":"10.3390/transplantology4040020","DOIUrl":"https://doi.org/10.3390/transplantology4040020","url":null,"abstract":"Objectives: Limited data are available on renal dysfunction and neurologic complications in heart failure in children, when the heart failure is not related to congenital heart disease (CHD) or cardiac surgery. This study used a multi-center database to describe pediatric heart failure (pHF)-related renal dysfunction, neurological complications, and outcomes in non-CHD patients. Methods: The Pediatric Health Information System (PHIS) database between 2004 and 2020 was used to analyze the prevalence of renal dysfunction and neurologic complications associated with pHF hospitalizations and their impact on outcomes. Results: Of the 5515 hospitalizations included in the study, renal dysfunction was identified in 1239 (22.5%), and neurologic dysfunction was diagnosed in 539 (9.8%). The diagnosis of renal or neurologic complications was associated with significantly higher use of ICU therapies, including mechanical ventilation, parenteral nutrition, and mechanical circulatory support. Patients with significant renal dysfunction were likely to receive kidney transplants in 3.1% of the cases. Neurologic complications were higher in patients with pHF who underwent heart transplantation (21.3% vs. 7.8%, p < 0.001). Patients with renal dysfunction and neurologic complications had significantly higher mortality rates than those without renal dysfunction (11.7% vs. 4.3%, p < 0.001) and neurologic complications (18.4% vs. 4.6%, p < 0.001). Conclusions: Renal dysfunction and neurologic complications are common, resulting in significantly higher utilization of ICU therapies and mortality rates during non-CHD-related pHF hospitalization. Neurologic complications associated with hospitalization for pHF are associated with a significantly higher mortality, which has been underemphasized in the literature. This study assesses the burden of these morbidities and highlights the importance of monitoring and managing renal and neurologic complications in pHF to improve outcomes.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"56 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134901680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-31DOI: 10.3390/transplantology4040019
Jane Y. Zhao, Doug A. Gouchoe, William E. Schwartzman, Justin P. Rosenheck, Victor Heh, Matthew C. Henn, Nahush A. Mokadam, David R. Nunley, Bryan A. Whitson, Asvin M. Ganapathi
A retrospective review of the UNOS/OPTN Database was performed from 1 October 1987–31 December 2019. Recipients were classified as LSu (15+ years survival without GF/ReTx), normal survival (3–15 years) and short survival (<3 years). In total, 22,646 patients were identified. Groups were assessed with comparative statistics in addition to a multivariate analysis which included recipient, donor, transplant characteristics and select post-transplant complications. LSu recipients were younger, more commonly female, healthier and more commonly had cystic fibrosis, pulmonary vascular disease or bilateral lung transplantation. LSu donors were younger, healthier and lacked clinical infection. Recipients with restrictive lung disease, single lung transplant and dialysis postoperatively were less likely to be LSu. Several recipient, donor and transplant characteristics are associated with long lung transplantation survival. While some factors cannot be altered, others related to donor selection and posttransplant management can potentially be influenced. Understanding these characteristics and employing discretion in donor selection, in appropriate recipients, may optimize the longevity of transplanted lungs.
{"title":"Long Survival Following Lung Transplantation: What Matters?","authors":"Jane Y. Zhao, Doug A. Gouchoe, William E. Schwartzman, Justin P. Rosenheck, Victor Heh, Matthew C. Henn, Nahush A. Mokadam, David R. Nunley, Bryan A. Whitson, Asvin M. Ganapathi","doi":"10.3390/transplantology4040019","DOIUrl":"https://doi.org/10.3390/transplantology4040019","url":null,"abstract":"A retrospective review of the UNOS/OPTN Database was performed from 1 October 1987–31 December 2019. Recipients were classified as LSu (15+ years survival without GF/ReTx), normal survival (3–15 years) and short survival (<3 years). In total, 22,646 patients were identified. Groups were assessed with comparative statistics in addition to a multivariate analysis which included recipient, donor, transplant characteristics and select post-transplant complications. LSu recipients were younger, more commonly female, healthier and more commonly had cystic fibrosis, pulmonary vascular disease or bilateral lung transplantation. LSu donors were younger, healthier and lacked clinical infection. Recipients with restrictive lung disease, single lung transplant and dialysis postoperatively were less likely to be LSu. Several recipient, donor and transplant characteristics are associated with long lung transplantation survival. While some factors cannot be altered, others related to donor selection and posttransplant management can potentially be influenced. Understanding these characteristics and employing discretion in donor selection, in appropriate recipients, may optimize the longevity of transplanted lungs.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"67 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135809649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-25DOI: 10.3390/transplantology4040018
Carmen A. Moes, C. Tji Gan, Leonie H. Venema, Roland F. Hoffmann, Barbro N. Melgert, Huib A. M. Kerstjens, Peter Olinga, Mitchel J. R. Ruigrok
Background: Donor lungs are often discarded, with gastric aspiration accounting for ~9% of lungs unsuitable for transplantation. To increase the donor pool, it is important to understand the pathophysiology of aspiration-induced lung damage (AILD) and to assess its treatment. Methods: Precision-cut lung slices (PCLS) were prepared from murine lungs and exposed to acid—pH 1.5 to 5.5—for 15 min. We also investigated whether acid-exposed slices (pH 3.5) could affect unexposed slices. In addition, we investigated whether dexamethasone (0.5 or 1 μM) could mitigate and treat the damage in each group. In each experiment (n = 3), we analyzed cell viability (ATP/protein content) and markers of inflammation (IL-1β, IL-6, TNF-𝛼, TRAIL). Results: PCLS subjected to pH 1.5–3.5 had a significantly reduced amount of ATP, albeit no increase in inflammation markers. There was no interaction of secretions from acid-exposed slices on unexposed slices. Dexamethasone had no beneficial effects in either group. Conclusion: Direct exposure to acid in the PCLS leads to a decrease in cell viability. Acid-exposed slices had no effect on the cell viability of unexposed slices. Treatment with dexamethasone offered no mitigation. More studies have to be performed to elucidate the pathophysiology of AILD and the possible treatment of aspiration-induced injury.
{"title":"Modelling Acid-Induced Lung Damage in Precision-Cut Lung Slices: An Ex Vivo Animal Model","authors":"Carmen A. Moes, C. Tji Gan, Leonie H. Venema, Roland F. Hoffmann, Barbro N. Melgert, Huib A. M. Kerstjens, Peter Olinga, Mitchel J. R. Ruigrok","doi":"10.3390/transplantology4040018","DOIUrl":"https://doi.org/10.3390/transplantology4040018","url":null,"abstract":"Background: Donor lungs are often discarded, with gastric aspiration accounting for ~9% of lungs unsuitable for transplantation. To increase the donor pool, it is important to understand the pathophysiology of aspiration-induced lung damage (AILD) and to assess its treatment. Methods: Precision-cut lung slices (PCLS) were prepared from murine lungs and exposed to acid—pH 1.5 to 5.5—for 15 min. We also investigated whether acid-exposed slices (pH 3.5) could affect unexposed slices. In addition, we investigated whether dexamethasone (0.5 or 1 μM) could mitigate and treat the damage in each group. In each experiment (n = 3), we analyzed cell viability (ATP/protein content) and markers of inflammation (IL-1β, IL-6, TNF-𝛼, TRAIL). Results: PCLS subjected to pH 1.5–3.5 had a significantly reduced amount of ATP, albeit no increase in inflammation markers. There was no interaction of secretions from acid-exposed slices on unexposed slices. Dexamethasone had no beneficial effects in either group. Conclusion: Direct exposure to acid in the PCLS leads to a decrease in cell viability. Acid-exposed slices had no effect on the cell viability of unexposed slices. Treatment with dexamethasone offered no mitigation. More studies have to be performed to elucidate the pathophysiology of AILD and the possible treatment of aspiration-induced injury.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135168762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-21DOI: 10.3390/transplantology4030017
Jes M. Sanders, Daniel Galvez, Xiaoqi Lin, Joseph Leventhal
Splenosis is a benign, acquired condition characterized by the auto-implantation of focal deposits of splenic tissue throughout the peritoneal cavity, most commonly occurring after splenic injury and/or splenectomy. Post-Transplant Lymphoproliferative Disorder (PTLD) is a well-known complication of solid organ transplantation that results from unregulated B-cell proliferation due to chronic immunosuppression. Given their clinical and radiologic similarities, these two entities may pose a diagnostic dilemma in select solid-organ transplant recipients. We present the case of a 54-year-old kidney-transplant recipient presenting with abdominal pain and found to have a retroperitoneal soft-tissue mass concerning for PTLD. He underwent a CT-guided biopsy of the mass, and histopathological studies revealed lymphoid tissue consistent with splenic tissue, thus ruling out PTLD. The patient subsequently underwent symptomatic management, with the eventual resolution of his symptoms. The early diagnosis of PTLD is paramount, as prompt intervention has a substantial impact on the high rate of morbidity and mortality associated with this condition. Additionally, the diagnosis of splenosis in the setting of a retroperitoneal mass is critical in order to avoid invasive diagnostic and therapeutic procedures that may result in significant complications. A detailed surgical history, including prior splenic trauma and/or splenectomy, should raise clinical suspicion for splenosis and guide further diagnostic and therapeutic decision making.
{"title":"Diagnostic Challenge in Renal Transplantation: Splenosis vs. Post-Transplant Lymphoproliferative Disorder—A Case Report","authors":"Jes M. Sanders, Daniel Galvez, Xiaoqi Lin, Joseph Leventhal","doi":"10.3390/transplantology4030017","DOIUrl":"https://doi.org/10.3390/transplantology4030017","url":null,"abstract":"Splenosis is a benign, acquired condition characterized by the auto-implantation of focal deposits of splenic tissue throughout the peritoneal cavity, most commonly occurring after splenic injury and/or splenectomy. Post-Transplant Lymphoproliferative Disorder (PTLD) is a well-known complication of solid organ transplantation that results from unregulated B-cell proliferation due to chronic immunosuppression. Given their clinical and radiologic similarities, these two entities may pose a diagnostic dilemma in select solid-organ transplant recipients. We present the case of a 54-year-old kidney-transplant recipient presenting with abdominal pain and found to have a retroperitoneal soft-tissue mass concerning for PTLD. He underwent a CT-guided biopsy of the mass, and histopathological studies revealed lymphoid tissue consistent with splenic tissue, thus ruling out PTLD. The patient subsequently underwent symptomatic management, with the eventual resolution of his symptoms. The early diagnosis of PTLD is paramount, as prompt intervention has a substantial impact on the high rate of morbidity and mortality associated with this condition. Additionally, the diagnosis of splenosis in the setting of a retroperitoneal mass is critical in order to avoid invasive diagnostic and therapeutic procedures that may result in significant complications. A detailed surgical history, including prior splenic trauma and/or splenectomy, should raise clinical suspicion for splenosis and guide further diagnostic and therapeutic decision making.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"80 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136236879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-06DOI: 10.3390/transplantology4030016
Hwarang S. Han, Michelle L. Lubetzky, Nidharshan S. Anandasivam, Rebecca A. Cox, Brian K. Lee
Immunoglobulin A nephropathy (IgAN) is the commonest glomerulonephritis worldwide, a category that represents the third most frequent cause of end-stage kidney disease (ESKD) in the United States. Kidney transplantation remains the optimal treatment of ESKD, and yet the prospects of IgAN recurrence post-transplant dampens the enthusiasm for living kidney donation in some instances, in addition to limiting the longevity of the kidney allograft. Moreover, the lack of a standardized method for detecting IgAN recurrence, since not all centers perform protocol allograft biopsies, has led to an underestimation of the extent of the issue. The pathogenesis of de novo IgAN remains conjectural, let alone the pathways for recurrent disease, but is increasingly recognized as a multi-hit injury mechanism. Identification of recurrent disease rests mainly on clinical symptoms and signs (e.g., hematuria, proteinuria) and could only be definitively proven with histologic evidence which is invasive and prone to sampling error. Treatment had relied mainly on nonspecific goals of proteinuria reduction, and in some cases, immunosuppression for active, crescentic disease. More recently, newer targets have the potential to widen the armamentarium for directed therapies, with more studies on the horizon. This review article provides an update on recurrent IgAN post-transplant.
{"title":"Recurrent Immunoglobulin A Nephropathy after Kidney Transplant—An Updated Review","authors":"Hwarang S. Han, Michelle L. Lubetzky, Nidharshan S. Anandasivam, Rebecca A. Cox, Brian K. Lee","doi":"10.3390/transplantology4030016","DOIUrl":"https://doi.org/10.3390/transplantology4030016","url":null,"abstract":"Immunoglobulin A nephropathy (IgAN) is the commonest glomerulonephritis worldwide, a category that represents the third most frequent cause of end-stage kidney disease (ESKD) in the United States. Kidney transplantation remains the optimal treatment of ESKD, and yet the prospects of IgAN recurrence post-transplant dampens the enthusiasm for living kidney donation in some instances, in addition to limiting the longevity of the kidney allograft. Moreover, the lack of a standardized method for detecting IgAN recurrence, since not all centers perform protocol allograft biopsies, has led to an underestimation of the extent of the issue. The pathogenesis of de novo IgAN remains conjectural, let alone the pathways for recurrent disease, but is increasingly recognized as a multi-hit injury mechanism. Identification of recurrent disease rests mainly on clinical symptoms and signs (e.g., hematuria, proteinuria) and could only be definitively proven with histologic evidence which is invasive and prone to sampling error. Treatment had relied mainly on nonspecific goals of proteinuria reduction, and in some cases, immunosuppression for active, crescentic disease. More recently, newer targets have the potential to widen the armamentarium for directed therapies, with more studies on the horizon. This review article provides an update on recurrent IgAN post-transplant.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"s1-14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85970978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-23DOI: 10.3390/transplantology4030015
D. Patrono, A. Apostu, G. Rizza, D. Cussa, A. Barreca, Selene Limoncelli, S. Mirabella, R. Romagnoli
Graft steatosis has been associated with inferior outcomes after liver transplantation. Given the rising prevalence of obesity and fatty liver disease, strategies allowing safe and successful utilization of fatty liver grafts are needed. Liver preservation by normothermic machine perfusion (NMP) allows reducing ischemia-reperfusion injury, extending preservation time and assessing graft viability prior to implantation into the recipient. NMP can be initiated at the donor hospital using a transportable device (referred to as upfront NMP or normothermic machine preservation) or after a period of cold ischemia (known as back-to-base). In this report, we present the case of a graft from an HCV-positive DBD donor with 70% macrovesicular steatosis, which was successfully preserved and transplanted using upfront NMP. This approach was key to minimize initial injury to the graft and allowed assessing its viability before transplantation, while improving transplant logistics. Upfront NMP represents a promising approach to enhance the transplantation of fatty liver grafts.
{"title":"Upfront Normothermic Machine Perfusion for a Liver Graft with Severe Macrovesicular Steatosis: A Proof-of-Concept Case","authors":"D. Patrono, A. Apostu, G. Rizza, D. Cussa, A. Barreca, Selene Limoncelli, S. Mirabella, R. Romagnoli","doi":"10.3390/transplantology4030015","DOIUrl":"https://doi.org/10.3390/transplantology4030015","url":null,"abstract":"Graft steatosis has been associated with inferior outcomes after liver transplantation. Given the rising prevalence of obesity and fatty liver disease, strategies allowing safe and successful utilization of fatty liver grafts are needed. Liver preservation by normothermic machine perfusion (NMP) allows reducing ischemia-reperfusion injury, extending preservation time and assessing graft viability prior to implantation into the recipient. NMP can be initiated at the donor hospital using a transportable device (referred to as upfront NMP or normothermic machine preservation) or after a period of cold ischemia (known as back-to-base). In this report, we present the case of a graft from an HCV-positive DBD donor with 70% macrovesicular steatosis, which was successfully preserved and transplanted using upfront NMP. This approach was key to minimize initial injury to the graft and allowed assessing its viability before transplantation, while improving transplant logistics. Upfront NMP represents a promising approach to enhance the transplantation of fatty liver grafts.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84330547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-08DOI: 10.3390/transplantology4030014
M. Salvadori
The presence in a recipient of antibodies directed against donor-specific antigens represents a major obstacle to transplantation. Removal of these antibodies represents a challenge for physicians dealing with kidney transplantation. Several strategies, techniques, and old and new drugs are currently used for desensitizing these patients. Desensitization may either occur before transplantation, at the time of transplantation, or after transplantation according to whether physicians are dealing with living or deceased donors. Different techniques may be used to reveal the presence of antibodies in the recipients; each technique has different sensitivities and specificities, and different advantages and drawbacks. The targets of the drugs used to desensitize are B cells, plasma cells, the antibodies themselves, and, finally, the complement that is the final actor causing tissue disruption. B cells are relatively easy to target; targeting the plasma cell is more difficult. Indeed, several new drugs are also used in randomized trials to defeat plasma cells. Antibodies may be removed easily, but their removal is often followed by antibody rebound. The complement is not easy to defeat and new drugs are currently used for this aim. Overall, despite difficulties, desensitization is currently possible in many cases, to obtain a safe and successful transplantation.
{"title":"Update on Desensitization Strategies and Drugs on Hyperimmune Patients for Kidney Transplantation","authors":"M. Salvadori","doi":"10.3390/transplantology4030014","DOIUrl":"https://doi.org/10.3390/transplantology4030014","url":null,"abstract":"The presence in a recipient of antibodies directed against donor-specific antigens represents a major obstacle to transplantation. Removal of these antibodies represents a challenge for physicians dealing with kidney transplantation. Several strategies, techniques, and old and new drugs are currently used for desensitizing these patients. Desensitization may either occur before transplantation, at the time of transplantation, or after transplantation according to whether physicians are dealing with living or deceased donors. Different techniques may be used to reveal the presence of antibodies in the recipients; each technique has different sensitivities and specificities, and different advantages and drawbacks. The targets of the drugs used to desensitize are B cells, plasma cells, the antibodies themselves, and, finally, the complement that is the final actor causing tissue disruption. B cells are relatively easy to target; targeting the plasma cell is more difficult. Indeed, several new drugs are also used in randomized trials to defeat plasma cells. Antibodies may be removed easily, but their removal is often followed by antibody rebound. The complement is not easy to defeat and new drugs are currently used for this aim. Overall, despite difficulties, desensitization is currently possible in many cases, to obtain a safe and successful transplantation.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82662346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-18DOI: 10.3390/transplantology4030013
Corey Mealer, Haley Konsek, Zachary Travis, Rebecca N. Suk, T. Rajab
Cold preservation is a key component to organ procurement and transplantation. Cold preservation functions by slowing metabolic activity of procured organs and begins the period known as cold ischemic time (CIT). Reducing CIT and warm ischemic time (WIT) are paramount to minimizing donor organ damage from ischemia and the build-up of waste products and signals that drive reperfusion injury prior to transplantation into a matching recipient. Preventing damage from CIT and WIT and extending the amount of time that organs can tolerate has been a major goal of organ transplantation since donors and recipients are frequently not located within the same hospital, region, or state. Meanwhile, the amount of CIT that a transplant center is willing to accept differs based on the organ, the institution receiving the organ offer, and the doctor receiving the offer for that institution. With the introduction of a partial heart transplantation conducted last year at Duke University, it is important to discuss how much CIT transplant centers conducting a partial heart transplantation (pHT) are willing to accept. This article will review the physiology of WIT and CIT, associated organ damage, CIT variation among transplant centers and organ types, and provide a brief discussion of the future of pHT-accepted CIT and the need for research in this field.
{"title":"Mechanisms of Cold Preservation and Reperfusion Injury for Solid Organ Transplantation: Implications for Partial Heart Transplantations","authors":"Corey Mealer, Haley Konsek, Zachary Travis, Rebecca N. Suk, T. Rajab","doi":"10.3390/transplantology4030013","DOIUrl":"https://doi.org/10.3390/transplantology4030013","url":null,"abstract":"Cold preservation is a key component to organ procurement and transplantation. Cold preservation functions by slowing metabolic activity of procured organs and begins the period known as cold ischemic time (CIT). Reducing CIT and warm ischemic time (WIT) are paramount to minimizing donor organ damage from ischemia and the build-up of waste products and signals that drive reperfusion injury prior to transplantation into a matching recipient. Preventing damage from CIT and WIT and extending the amount of time that organs can tolerate has been a major goal of organ transplantation since donors and recipients are frequently not located within the same hospital, region, or state. Meanwhile, the amount of CIT that a transplant center is willing to accept differs based on the organ, the institution receiving the organ offer, and the doctor receiving the offer for that institution. With the introduction of a partial heart transplantation conducted last year at Duke University, it is important to discuss how much CIT transplant centers conducting a partial heart transplantation (pHT) are willing to accept. This article will review the physiology of WIT and CIT, associated organ damage, CIT variation among transplant centers and organ types, and provide a brief discussion of the future of pHT-accepted CIT and the need for research in this field.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"303 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72422307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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