Mesenchymal Stem Cells to Treat Digestive System Disorders: Progress Made and Future Directions
AbstractPurpose of ReviewThe purpose of this review is to summarize the results from clinical trials that evoked promise and discouragement for the use of mesenchymal stem cells (MSCs) to treat digestive system disorders.Recent FindingsAdult MSCs are defined as a non-homogeneous population of pluripotent progenitor cells, which can be isolated and expanded in vitro from different tissues. The differentiation capacity of MSC along mesenchymal lineages and their immunomodulatory properties have been considered a new therapeutic approach for intestinal disorders. A dysregulated immune response is the cause and sustainment of ...
Source: Current Transplantation Reports - April 23, 2019 Category: Transplant Surgery Source Type: research
Liver Bioengineering: Promise, Pitfalls, and Hurdles to Overcome
AbstractPurpose of ReviewIn this review, we discuss the recent advancements in liver bioengineering and cell therapy and future advancements to improve the field towards clinical applications.Recent Findings3D printing, hydrogel-based tissue fabrication, and the use of native decellularized liver extracellular matrix as a scaffold are used to develop whole or partial liver substitutes. The current focus is on developing a functional liver graft through achieving a non-leaky endothelium and a fully constructed bile duct. Use of cell therapy as a treatment is less invasive and less costly compared to transplantation, however...
Source: Current Transplantation Reports - March 24, 2019 Category: Transplant Surgery Source Type: research
Evasion of Pre-Existing Immunity to Cas9: a Prerequisite for Successful Genome Editing In Vivo?
AbstractPurpose of ReviewCRISPR-Cas9-mediated genome editing holds promise for the future correction of congenital defects in vivo, providing potentially curative interventions for numerous intractable diseases. Nevertheless, the bacterial origin of the Cas9 endonuclease raises the spectre of pre-existing immunity that threatens to undermine the success of this powerful technology, necessitating a careful assessment of the potential risks involved.Recent FindingsGiven that genome editing commonly exploits the specificity of Cas9 endonucleases from species of bacteria that are a common cause of infection in humans, the rece...
Source: Current Transplantation Reports - March 18, 2019 Category: Transplant Surgery Source Type: research
Cell Therapy: Past, Present, and Future
AbstractPurpose of ReviewCellular therapy started in the early twentieth century with the development of blood transfusion and later bone marrow transplantation. This review describes the historical origins and major milestones in the field of cellular therapy. We discuss ethical concerns associated with certain cell sources and how they influenced therapy strategies. A focus of this article is on the use of stem cells to understand regenerative repair after kidney injury. In addition, we give an overview over past and current kidney-related cellular therapy trials.Recent FindingsThe number of kidney-related cellular thera...
Source: Current Transplantation Reports - March 17, 2019 Category: Transplant Surgery Source Type: research
Hyperlipidemia and Allograft Rejection
AbstractPurpose of ReviewAdvances in the development of immunosuppressive drug regimens have led to impressive survival rates in the year following organ transplantation. However, rates of long-term graft dysfunction remain undesirably high. Recently, it has been shown that co-morbidities in the patient population may affect graft survival. In mouse models, hyperlipidemia, a co-morbidity present in the majority of cardiac transplant patients, can significantly alter T cell responses to cardiac and skin allografts and accelerate graft rejection. Here, we review recent advances in our understanding of how alterations in lipi...
Source: Current Transplantation Reports - February 26, 2019 Category: Transplant Surgery Source Type: research
Should Hepatitis C Donors Be Used in Na ïve Urgent Status Patients on the Heart Transplant Waitlist?
AbstractPurpose of ReviewThe aim of this commentary is to review contemporary data on the use of hearts from hepatitis C positive donors.Recent FindingsThere continues to be a critical shortage of suitable heart donors available for patients with advanced heart failure requiring transplantation. Historically, donors with chronic hepatitis C virus were not utilized for heart transplantation due to concern about poor post-transplant outcomes. This was due, in part, to concerns about successfully treating chronic hepatitis C after transmitting the infection from donor to recipient. The availability of direct-acting anti-viral...
Source: Current Transplantation Reports - February 12, 2019 Category: Transplant Surgery Source Type: research
Frailty and Long-Term Post-Kidney Transplant Outcomes
AbstractPurpose of ReviewTo highlight recent research about frailty and its role as a predictor of adverse, long-term post-kidney transplant (KT) outcomes.Recent FindingsFrailty is easily measured using the physical frailty phenotype (PFP) developed by gerontologist Dr. Linda Fried and colleagues. In recent studies,> 50% of KT recipients were frail (20%) or intermediately frail (32%) at KT admission. Frail recipients were at 1.3-times higher risk of immunosuppression intolerance and 2.2-times higher risk of mortality, even after accounting for recipient, donor, and transplant factors; these findings were cons istent ...
Source: Current Transplantation Reports - February 9, 2019 Category: Transplant Surgery Source Type: research
The Evolving Role of Neutrophils in Liver Transplant Ischemia-Reperfusion Injury
AbstractPurpose of ReviewHepatic ischemia-reperfusion injury (IRI), an inevitable event during liver transplantation, represents a major risk factor for the primary graft dysfunction as well as the development of acute and chronic rejection. Neutrophils, along macrophages, are pivotal in the innate immune-driven liver IRI, whereas the effective neutrophil-targeting therapies remain to be established. In this review, we summarize progress in our appreciation of the neutrophil biology and discuss neutrophil-based therapeutic perspectives.Recent FindingsNew technological advances enable to accurately track neutrophil movement...
Source: Current Transplantation Reports - January 29, 2019 Category: Transplant Surgery Source Type: research
A Contraindication for Transplantation? Consequences of Frailty on Immunity and Immunosuppression
AbstractPurpose of ReviewFrailty has gained clinical relevance. While the condition may negatively impact outcomes, organ transplantation may also improve frailty. Notably, available assessment tools are broad and have not allowed for a detailed analysis or prognosis.Recent FindingsFrailty has been linked to adverse surgical outcomes while imparting on immune competency. Immunosuppressive treatment may therefore require modifications in frail patients, and effects on drug metabolism may need consideration. Moreover, cognitive impairment may impact compliance. Here, we provide a comprehensive update on clinical features, di...
Source: Current Transplantation Reports - January 28, 2019 Category: Transplant Surgery Source Type: research
Implications of Frailty for Peritransplant Outcomes in Kidney Transplant Recipients
AbstractPurpose of ReviewResearch over the past few decades points to the importance of frailty, or the lack of physiologic reserve, in the natural history of chronic diseases and in modifying the impact of potential interventions. End-stage kidney disease (ESKD) and the intervention of kidney transplantation are no exception. We review the recent epidemiologic and cohort-based evidence on the association between frailty and kidney transplant outcomes and provide a framework of questions with which to approach future research endeavors and clinical practice.Recent FindingsFrailty in kidney transplant candidates can be meas...
Source: Current Transplantation Reports - January 26, 2019 Category: Transplant Surgery Source Type: research
Metrics of Aging in Transplantation
AbstractPurpose of ReviewTo describe potential metrics of aging beyond chronological age and their associations with outcomes after solid organ transplantation.Recent FindingsInvestigation in this field has focused primarily on two areas: biomarkers related to replicative cell senescence and frailty and constructs related to frailty (e.g., sarcopenia, physical performance). Indicators of replicative senescence and frailty are more prevalent among transplant candidates than in the general elderly population, and both have been shown in recent studies to be associated with adverse outcomes following transplantation.SummaryDe...
Source: Current Transplantation Reports - January 25, 2019 Category: Transplant Surgery Source Type: research
Measuring Alloreactive B Cell Responses in Transplant Recipients
AbstractPurpose of ReviewDespite advanced immunosuppression, donor-specific antibodies (DSA) remain the leading cause of acute and chronic transplant tissue injury. Comprehensive evaluation of anti-donor humoral immune responses is critical for successful prevention, diagnosis, and treatment of antibody-mediated rejection. This review summarizes the evolution of techniques used for this purpose in experimental and clinical transplantation.Recent FindingsFor decades, measuring DSA serum levels was the only way to assess recipient humoral immunity. Recently, the interest shifted from quantifying circulating DSA to the analys...
Source: Current Transplantation Reports - January 24, 2019 Category: Transplant Surgery Source Type: research
Sarcopenia in Liver Transplantation
AbstractPurpose of ReviewSarcopenia is highly prevalent in end-stage liver disease (ESLD) patients and has been linked to poor outcomes on the wait list and post-transplantation. This current perspectives article reviews the ongoing challenges to define sarcopenia in ESLD patients, describes associations of sarcopenia with wait list and post-transplantation outcomes, and provides summarized data on efforts to prevent and treat sarcopenia through novel interventions.Recent FindingsSupervised exercise programs improve muscle strength, but muscle mass outcomes are limited by short study follow-up times. Branched-chain amino a...
Source: Current Transplantation Reports - January 21, 2019 Category: Transplant Surgery Source Type: research
The Role of Secretory Leukocyte Proteinase Inhibitor During Transplantation
AbstractPurpose of ReviewOld and new players of the innate immune response have been studied in the context of transplantation. Nonetheless, little interest has been focused toward the immune regulatory feedback in transplantation. Here, we revised the role of secretory leukocyte proteinase inhibitor (SLPI), which limits the activity of serine proteases, in solid organ transplantation.Recent FindingsIschemia-reperfusion injury increases SLPI gene expression. Furthermore, post-transplant acute kidney injury increases the expression of SLPI transcript and protein. Several studies have shown that SLPI exerts direct, indirect,...
Source: Current Transplantation Reports - January 16, 2019 Category: Transplant Surgery Source Type: research
Role of Complement Activation in Allograft Inflammation
AbstractPurpose of ReviewNovel paradigms have broadened our understanding of mechanisms through which complement mediates allograft inflammation/injury. Herein, we review advances in the field and highlight therapeutic implications.Recent FindingsPre-clinical and translational human trials have elucidated complement-dependent mechanisms of post-transplant ischemia-reperfusion (I/R) injury. Immune cell-derived, and intracellular, complement activation is newly linked to proinflammatory T cell immunity relevant to allograft rejection. Complement-induced immune regulation, including C5a ligation of C5a receptor 2 on T cells, ...
Source: Current Transplantation Reports - January 15, 2019 Category: Transplant Surgery Source Type: research
