Will cell therapies provide the solution for the shortage of transplantable organs?

Purpose of review The potential to regenerate ischemically damaged kidneys while being perfused ex-vivo offers the best near-term solution to increasing kidney allografts for transplantation. Recent findings There are a number of stem-cell sources including: stromal mesenchymal cells (MSC), induced adult pluripotent stem cells, fetal stem cells from placenta, membranes, amniotic fluid and umbilical cord and hematopoietic cells. MSC are increasingly the stem cell of choice and studies are primarily focused on novel induction immunosuppression to prevent rejection. Stem-cell therapies applied in vivo may be of limited benefit because the nonintegrating cells do not remain in the kidney and are not detectable in the body after several days. MSC therapies for transplantation have demonstrated early safety and feasibility. However, efficacy has not been clearly established. A more feasible application of a stem-cell therapy in transplantation is the administration of MSC to treat damaged renal allografts directly while being perfused ex vivo. Initial feasibility has been established demonstrating MSC-treatment results in statistically significant reduction of inflammatory responses, increased ATP and growth factor synthesis and mitosis. Summary The ability to regenerate renal tissue ex-vivo sufficiently to result in immediate function could revolutionize transplantation by solving the chronic organ shortage.
Source: Current Opinion in Organ Transplantation - Category: Surgery Tags: ORGANOGENESIS: Edited by Giuseppe Orlando Source Type: research

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Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: While there is a certain overlap between the results of the current study and published transcriptomic profiles of non-transplanted livers with steatosis, we have identified discrete characteristics of the non-alcoholic fatty liver disease in liver grafts potentially utilizable for the establishment of predictive signature. Introduction Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized countries, its prevalence being estimated at 19–31.3% (1). It encompasses a range of conditions that are thought to arise from fatty liver (simple steatosis) throu...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Joanna Mikulak1,2, Elena Bruni1,2, Ferdinando Oriolo1,2, Clara Di Vito1 and Domenico Mavilio1,2* 1Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Milan, Italy 2Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy The liver is considered a preferential tissue for NK cells residency. In humans, almost 50% of all intrahepatic lymphocytes are NK cells that are strongly imprinted in a liver-specific manner and show a broad spectrum of cellular heterogeneity. Hepatic NK (he-NK) cells play key roles in tuning liver immune response in b...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Qiancheng Deng1, Yangyang Luo1,2, Christopher Chang3, Haijing Wu1, Yan Ding4* and Rong Xiao1* 1Hunan Key Laboratory of Medical Epigenetics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, China 2Department of Dermatology, Hunan Children's Hospital, Changsha, China 3Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, United States 4Department of Dermatology, Hainan Provincial Dermatology Disease Hospital, Haikou, China Autoimmune diseases are usually complex and multifactorial, characterized by aberrant produc...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions Lymphatic vessels, like blood vessels, are a highly interactive surface for cells of the immune system, and through the use of chemokines and their receptors can coordinate key interactions. These pathways can control the entry and function of particular immune subsets in a number of pathological conditions. Nonetheless LECs have distinct patterns of chemokine secretion and expression of chemokine receptors that distinguish them from the blood vessel system and mediate distinct roles and responses. The abundance and diversity of the chemokine family point to the likelihood that a plethora of novel chemokine fu...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion: Mesenchymal stem cell transplantation could be use as a potential treatment for PHLF. Introduction Partial hepatectomy is an important treatment for benign and malignant liver diseases. Although the liver can be completely regenerated after partial excision or injury, at least 1/3 of the liver should be retained in most of the patients, and 40–50% should be retained in patients with parenchymal liver disease (Adams et al., 2013; Cieslak et al., 2014). Postoperative complications, such as acute post-hepatectomy liver failure (PHLF) or small liver syndrome, may occur when the scope of excision is to...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Maria Schreiber1,2, Marc Weigelt1,3, Anne Karasinsky1, Konstantinos Anastassiadis4, Sonja Schallenberg2, Cathleen Petzold2, Ezio Bonifacio1,3*, Karsten Kretschmer2,3*† and Angela Hommel1,3*† 1Preclinical Approaches to Stem Cell Therapy/Diabetes, DFG-Center for Regenerative Therapies Dresden Cluster of Excellence, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany 2Molecular and Cellular Immunology/Immune Regulation, DFG-Center for Regenerative Therapies Dresden Cluster of Excellence, Center for Molecular and Cellular Bioengineering, Technische Unive...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions To our knowledge, our work is the first to have demonstrated actual renal regeneration while ischemically damaged human kidneys are perfused ex vivo for 24 hours. The observed regeneration entails: increased synthesis of adenosine triphosphate, a reduced inflammatory response, increased synthesis of growth factors, normalization of the cytoskeleton and mitosis. The ability to regenerate renal tissue ex vivo sufficiently to result in immediate function could revolutionize transplantation by solving the chronic organ shortage.
Source: Transplantation - Category: Transplant Surgery Tags: Original Basic Science—General Source Type: research
Conclusions All patients with transplant-associated thrombotic microangiopathy should be screened for the causes of CD. C5 inhibition with eculizumab is an important therapeutic resource to manage this complication. When KTx is necessary, immunosuppression can be safely withhold in case of same donor for both grafts and documented full chimerism.
Source: Transplantation - Category: Transplant Surgery Tags: Original Clinical Science—General Source Type: research
ConclusionsWe have shown for the first time that TSP-1, PF4,and GAL-1 are associated with engraftment in patients with SCD who undergo haplo HSCT. The study warrants further validation in a larger sample size as well as in vitro and in vivo analyses to evaluate whether our candidate proteins are associated with tolerance induction.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Comorbidity and Novel Strategies to Improve Graft Function Source Type: research
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