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Frontiers in Immunology 2023Solid organ and composite tissue allotransplanation have been widely applied to treat end-stage organ failure and massive tissue defects, respectively. Currently there... (Review)
Review
Solid organ and composite tissue allotransplanation have been widely applied to treat end-stage organ failure and massive tissue defects, respectively. Currently there are a lot of research endeavors focusing on induction of transplantation tolerance, to relieve the burden derived from long-term immunosuppressant uptake. The mesenchymal stromal cells (MSCs) have been demonstrated with potent immunomodulatory capacities and applied as promising cellular therapeutics to promote allograft survival and induce tolerance. As a rich source of adult MSCs, adipose tissue provides additional advantages of easy accessibility and good safety profile. In recent years, the stromal vascular fraction (SVF) isolated from adipose tissues following enzymatic or mechanical processing without culture and expansion has demonstrated immunomodulatory and proangiogenic properties. Furthermore, the secretome of AD-MSCs has been utilized in transplantation field as a potential "cell-free" therapeutics. This article reviews recent studies that employ these adipose-derived therapeutics, including AD-MSCs, SVF, and secretome, in various aspects of organ and tissue allotransplantation. Most reports validate their efficacies in prolonging allograft survival. Specifically, the SVF and secretome have performed well for graft preservation and pretreatment, potentially through their proangiogenic and antioxidative capacities. In contrast, AD-MSCs were suitable for peri-transplantation immunosuppression. The proper combination of AD-MSCs, lymphodepletion and conventional immunosuppressants could consistently induce donor-specific tolerance to vascularized composite allotransplants (VCA). For each type of transplantation, optimizing the choice of therapeutics, timing, dose, and frequency of administration may be required. Future progress in the application of adipose-derived therapeutics to induce transplantation tolerance will be further benefited by continued research into their mechanisms of action and the development of standardized protocols for isolation methodologies, cell culture, and efficacy evaluation.
Topics: Humans; Adult; Transplantation Tolerance; Cells, Cultured; Mesenchymal Stem Cells; Adipose Tissue; Immunosuppression Therapy; Immunosuppressive Agents
PubMed: 37187733
DOI: 10.3389/fimmu.2023.1111813 -
Liver Transplantation : Official... Jun 2024This review discusses long-term complications from immunosuppressants after liver transplantation and the management of these complications. Common complications of... (Review)
Review
This review discusses long-term complications from immunosuppressants after liver transplantation and the management of these complications. Common complications of calcineurin inhibitors include nephrotoxicity and metabolic diseases. Nephrotoxicity can be managed by targeting a lower drug level and/or adding an immunosuppressant of a different class. Metabolic disorders can be managed by treating the underlying condition and targeting a lower drug level. Gastrointestinal adverse effects and myelosuppression are common complications of antimetabolites that are initially managed with dose reduction or discontinuation if adverse events persist. Mammalian targets of rapamycin inhibitors are associated with myelosuppression, proteinuria, impaired wound healing, and stomatitis, which may require dose reduction or discontinuation. Induction agents and agents used for steroid-refractory rejection or antibody-mediated rejection are reviewed. Other rare complications of immunosuppressants are discussed as well.
Topics: Humans; Immunosuppressive Agents; Liver Transplantation; Graft Rejection; Calcineurin Inhibitors; Kidney Diseases; Immunosuppression Therapy; Metabolic Diseases; MTOR Inhibitors
PubMed: 38315054
DOI: 10.1097/LVT.0000000000000341 -
Seminars in Arthritis and Rheumatism Dec 2019Systemic sclerosis (scleroderma; SSc) is an autoimmune rheumatic disease with high clinical burden and unmet need due to connective tissue fibrosis and vascular damage.... (Review)
Review
Systemic sclerosis (scleroderma; SSc) is an autoimmune rheumatic disease with high clinical burden and unmet need due to connective tissue fibrosis and vascular damage. It has the highest case specific mortality of any rheumatic disease, with approximately half of patients diagnosed eventually dying as a direct result of SSc. There are no approved diseases modifying treatments. This is partly related to the difficulty of conducting clinical trials for regulatory approval. Traditionally skin thickness has been assessed using the modified Rodnan skin score (MRSS) that has been shown to correlate with survival and risk of complications in SSc. However recent trials have highlighted the limitations of MRSS which often improves over time, even on placebo. A new composite measure integrating changes in multiple domains of lung function, skin, patients and physician global and HAQ disability index has been developed, the CRISS (Composite Response Index for Systemic Sclerosis). This measure looks promising and has provisional acceptance by American College of Rheumatology (designated ACR CRISS) but is unlikely to be strongly persuasive to Health Authorities in isolation unless there are also clinically meaningful changes in relevant domains that reflect how patients feel, function or survive.
Topics: Clinical Trials as Topic; Disease Management; Humans; Immunosuppression Therapy; Scleroderma, Systemic
PubMed: 31779848
DOI: 10.1016/j.semarthrit.2019.09.019 -
Langenbeck's Archives of Surgery Jul 2015To give an overview over cell therapeutic approaches to immunosuppression in clinical kidney transplantation. A focus is on myeloid suppressor cell therapy by mitomycin... (Review)
Review
PURPOSE
To give an overview over cell therapeutic approaches to immunosuppression in clinical kidney transplantation. A focus is on myeloid suppressor cell therapy by mitomycin C-induced cells (MICs).
METHODS
Literature review with an emphasis on already existing therapies.
RESULTS
Several cell therapeutic approaches to immunosuppression and donor-specific unresponsiveness are now being tested in early phase I and phase II trials in clinical kidney transplantation. Cell products such as regulatory T cells or regulatory macrophages, or other myeloid suppressor cell therapies, may either consist of donor-specific, third-party, or autologous cell preparations. Major problems are the identification of the suppressive cell populations and their expansion to have sufficient amount of cells to achieve donor unresponsiveness (e.g., with regulatory T cells). We show a simple and safe way to establish donor unresponsiveness in living-donor kidney transplantation by MIC therapy. A phase I clinical trial is now under way to test the safety and efficacy of this cell therapeutic approach.
CONCLUSIONS
Cell therapeutic approaches to immunosuppression after kidney transplantation may revolutionize clinical transplantation in the future.
Topics: Cell- and Tissue-Based Therapy; Graft Survival; Humans; Immune Tolerance; Immunosuppression Therapy; Kidney Transplantation
PubMed: 26077202
DOI: 10.1007/s00423-015-1313-z -
Clinical Obstetrics and Gynecology Mar 2022Pharmacologic immunosuppression is required for the success of uterus transplantation but can provoke several complications for the transplant recipient. In this review,... (Review)
Review
Pharmacologic immunosuppression is required for the success of uterus transplantation but can provoke several complications for the transplant recipient. In this review, we discuss the immunologic complications that can occur in the uterus transplant recipient. First, we provide the latest update on immunosuppression regimens used by programs throughout the world. Next, we discuss the prevalence, mechanisms, treatment, and outcome of rejection in uterus transplant recipients. Finally, we discuss infectious complications of varying severity alongside their treatment and impact.
Topics: Female; Graft Rejection; Humans; Immunosuppression Therapy; Uterus
PubMed: 35045023
DOI: 10.1097/GRF.0000000000000686 -
Advanced Healthcare Materials Aug 2023Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), two immunosuppressive myeloid components within the tumor microenvironment (TME),...
Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), two immunosuppressive myeloid components within the tumor microenvironment (TME), represent fundamental barriers in cancer immunotherapy, whereas current nanomedicines rarely exert dual modulatory roles on these cell types simultaneously. Reactive oxygen species (ROS) not only mediates MDSC-induced immunosuppression but also triggers differentiation and polarization of M2-TAMs. Herein, an ROS scavenging nanozyme, Zr-CeO, with enhanced superoxide dismutase- and catalase-like activities for renal tumor growth inhibition is reported. Mechanistically, intracellular ROS scavenging by Zr-CeO significantly attenuates MDSC immunosuppression via dampening the unfolded protein response, hinders M2-TAM polarization through the ERK and STAT3 pathways, but barely affects neoplastic cells and cancer-associated fibroblasts. Furthermore, Zr-CeO enhances the antitumor effect of PD-1 inhibition in murine renal and breast tumor models, accompanied with substantially decreased MDSC recruitment and reprogrammed phenotype of TAMs in the tumor mass. Upon cell isolation, reversed immunosuppressive phenotypes of MDSCs and TAMs are identified. In addition, Zr-CeO alone or combination therapy enhances T lymphocyte infiltration and IFN-γ production within the TME. Collectively, a promising strategy to impair the quantity and function of immunosuppressive myeloid cells and sensitize immunotherapy in both renal and breast cancers is provided.
Topics: Animals; Mice; Reactive Oxygen Species; Immunosuppression Therapy; Immune Tolerance; Myeloid Cells; Neoplasms; Tumor Microenvironment; Immunotherapy
PubMed: 37031357
DOI: 10.1002/adhm.202300191 -
The International Journal of Lower... Sep 2015Hidradenitis suppurativa (HS) is a chronic, burdensome, debilitating disease of the hair follicle. It presents with recurrent painful inflamed and noninflamed lesions... (Review)
Review
Hidradenitis suppurativa (HS) is a chronic, burdensome, debilitating disease of the hair follicle. It presents with recurrent painful inflamed and noninflamed lesions usually in specific body areas such as axillary, inguinal, perineal, and genital areas. It is associated with a large range of other diseases and conditions, such as obesity, arthropathy, inflammatory bowel diseases, and sqaumous cell carcinoma. Medical therapy may be systemic or topical, mainly based on antibiotics, retinoids, hormones and immunosuppressive drugs, including biological therapies. Surgical and laser therapies may be a valid therapeutic approach in order to treat locally recurring lesions. The aim of this article is to review the wound healing options after skin excision and laser treatments, with a focus on lesions left to heal by secondary intention, analyzing the efficacy of moist wound dressings, negative pressure wound therapy, bioactive dressings, such as platelet-rich plasma gel and hylarunoic acid scaffold, or autologous keratinocyte suspension in platelet concentrate and skin-grafting tecniques.
Topics: Disease Management; Hidradenitis Suppurativa; Humans; Immunosuppression Therapy; Recurrence; Wound Healing
PubMed: 26248827
DOI: 10.1177/1534734615598890 -
American Journal of Kidney Diseases :... Feb 2017A wish for progress in transplantation assumes that there are needs not met by the currently available therapy and that the barriers to resolving the problems can be... (Review)
Review
A wish for progress in transplantation assumes that there are needs not met by the currently available therapy and that the barriers to resolving the problems can be surmounted. There are 5 major unmet needs: the potential to avoid transplantation either by prevention of disease or provision of an alternative to natural biological organ replacement; geographic heterogeneity of access to, and quality of, transplantation; availability of transplantation to those in need of it; survival of the patient and the transplant; and the avoidance of adverse effects of immunosuppression. During the past 50 years, there have been advances on at least 4 of these 5 fronts that illustrate the interplay of "big steps" and "marginal gains" in the following areas: surgical technique, testing the immunologic barriers, introduction of chemical and biological immunosuppression, and prophylaxis for microbial infections. The potential for further improvement comes in 5 major areas: blood biomarkers for monitoring of rejection, drug-free transplantation through the development of stable tolerance, eliminating the impact of ischemia-reperfusion injury, xenotransplantation of porcine kidneys, and finally, the possibility of autologous regeneration of functioning kidney tissue to treat advanced kidney disease.
Topics: Animals; Biomedical Research; Health Services Needs and Demand; Humans; Immunosuppression Therapy; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Postoperative Complications; Quality Improvement; Renal Replacement Therapy; Time Factors
PubMed: 27823818
DOI: 10.1053/j.ajkd.2016.08.024 -
Transplantation Proceedings 2020As newer immunosuppression has steadily induced tolerance and improved the survival time of graft, malignancy after lung transplantation has become an important cause of... (Review)
Review
As newer immunosuppression has steadily induced tolerance and improved the survival time of graft, malignancy after lung transplantation has become an important cause of mortality. Cancer is the third most frequent cause of death among lung recipients who survive more than 1 year, and the oncogenic risk is believed to be directly related to the cumulative dose of immunosuppression and the drug family. Immunosuppression modification is the initial management to malignancy in transplant recipients. Adjustment of agent dosage and scheme to the minimum level where graft-organ function is still maintained is advised, although the precise modification of immunosuppression has not been studied prospectively. However, there is still no recommendation or guidelines of immunosuppression therapy scheme in lung transplant recipients after diagnosed malignancy. Some signal centers reported their experiences, but the evidence is scant because of the low quality of the available studies. It's the time to call for more high-quality data and clinical trials to explore a better immunosuppression scheme for lung transplant recipients with malignancy.
Topics: Graft Rejection; Humans; Immunocompromised Host; Immunosuppression Therapy; Immunosuppressive Agents; Lung Transplantation; Neoplasms; Transplant Recipients
PubMed: 31948800
DOI: 10.1016/j.transproceed.2019.09.012 -
Current Opinion in Hematology Nov 2017Improvements in allogeneic hematopoietic cell transplantation (HCT) with better donor selection, conditioning regimens and graft vs. host disease prophylaxis make it... (Review)
Review
PURPOSE OF REVIEW
Improvements in allogeneic hematopoietic cell transplantation (HCT) with better donor selection, conditioning regimens and graft vs. host disease prophylaxis make it reasonable to move HCT earlier in the algorithm for management of severe aplastic anemia (SAA). Recent progress in transplantation is reviewed whereas issues related to developing countries are also addressed.
RECENT FINDINGS
Multiple research centers are reporting on clonality, mutations and telomere disorders in SAA, which may help to choose the most appropriate therapy upfront. Eltrombopag, in combination with immunosuppressive therapy (IST), has shown remarkable improvement over historical IST, and long-term follow-up is awaited. In younger patients and in experienced centers, matched unrelated-donor (MUD) and related haploidentical transplants (haplo-HCT) are being reported with survival approaching that seen with sibling transplants. Literature from resource-limited countries highlight the need to modify guidelines to make them affordable and cost-effective. Bone marrow remains the graft source of choice; peripheral blood stem cells may be acceptable in special circumstances in resource-constrained countries.
SUMMARY
The potential of novel research findings and new therapeutic trials should be maximized by validation in different centers, countries and patient populations to provide personalized care to patients with aplastic anemia.
Topics: Allografts; Anemia, Aplastic; Benzoates; Hematopoietic Stem Cell Transplantation; Humans; Hydrazines; Immunosuppression Therapy; Practice Guidelines as Topic; Pyrazoles
PubMed: 28877042
DOI: 10.1097/MOH.0000000000000382