In utero transplantation

INTRODUCTION: Kidney transplantation (KT) restores the fertility of women with end-stage kidney disease (ESKD), thus offering them the possibility of having children. However, pregnancy after kidney transplantation is associated with high maternal-fetal morbidity. The purpose of this work is to report the experience of our service in pregnancies in kidney transplant recipients. MATERIALS AND METHODS: We retrospectively studied the records of transplant recipients who had one or more pregnancies after KT...

The transplantation of neural progenitors into a host brain represents a useful tool to evaluate the involvement of cell-autonomous processes and host local cues in the regulation of neuronal differentiation during the development of the mammalian brain. Human brain development starts at the embryonic stages, in utero, with unique properties at its neotenic stages. We analyzed the engraftment and differentiation of human neuronal progenitor cells (hNPCs) transplanted in utero into the mouse brain. The influence of the environment was studied by transplanting human NPCs within the lateral ventricles (LV), compared with the prefrontal cortex (PFC) of immunocompetent mice...

BACKGR OUND: T-cell receptor excision circle (TREC)-based newborn screening (NBS) for severe combined immunodeficiencies (SCID) was introduced in Germany in August 2019. METHODS: Children with abnormal TREC-NBS were referred to a newly established network of Combined Immunodeficiency (CID) Clinics and Centers. The Working Group for Pediatric Immunology (API) and German Society for Newborn Screening (DGNS) performed 6-monthly surveys to assess the TREC-NBS process after 2...

The retinal pigment epithelium (RPE) forms an important cellular monolayer, which contributes to the normal physiology of the eye. Damage to the RPE leads to the development of degenerative diseases, such as age-related macular degeneration (AMD). Apart from acting as a physical barrier between the retina and choroidal blood vessels, the RPE is crucial in maintaining photoreceptor (PR) and visual functions. Current clinical intervention to treat early stages of AMD includes stem cell-derived RPE transplantation, which is still in its early stages of evolution...

Gut microbes and their metabolites are actively involved in the development and regulation of host immunity, which can influence disease susceptibility. Herein, we review the most recent research advancements in the gut microbiota-immune axis. We discuss in detail how the gut microbiota is a tipping point for neonatal immune development as indicated by newly uncovered phenomenon, such as maternal imprinting, in utero intestinal metabolome, and weaning reaction. We describe how the gut microbiota shapes both innate and adaptive immunity with emphasis on the metabolites short-chain fatty acids and secondary bile acids...

Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disorder caused by pathogenic variants in GBE1 which results in reduced or deficient glycogen branching enzyme activity. Consequently, glycogen synthesis is impaired and leads to accumulation of poorly branched glycogen known as polyglucosan. GSD IV is characterized by a remarkable degree of phenotypic heterogeneity with presentations in utero, during infancy, early childhood, adolescence, or middle to late adulthood. The clinical continuum encompasses hepatic, cardiac, muscular, and neurologic manifestations that range in severity...

In utero hematopoietic cell transplantation (IUHCT) is an experimental treatment for congenital hemoglobinopathies including Sickle cell disease and thalassemias. One of the principle advantages of IUHCT is the predisposition of the developing fetus toward immunologic tolerance. This allows for engraftment across immune barriers without immunosuppression and, potentially, decreased susceptibility to graft-versus-host-disease (GVHD). We demonstrate fetal resistance to GVHD following T cell-replete allogeneic hematopoietic cell transplantation compared to the neonate...

Significant advances in maternal-fetal medicine and gene sequencing technology have fostered a new frontier of in utero molecular and cellular therapeutics, including gene editing, enzyme replacement therapy, and stem cell transplantation to treat single-gene disorders with limited postnatal treatment strategies. In utero therapies take advantage of unique developmental properties of the fetus to allow for the correction of monogenic disorders before irreversible disease pathology develops. While early preclinical studies in animal models are encouraging, more studies are needed to further evaluate their safety and efficacy prior to widespread clinical use...

Introduction: Duchenne muscular dystrophy (DMD) is a progressive disease that leads to damage of muscle and myocardium due to genetic abnormalities in the dystrophin gene. In utero cell transplantation that might facilitate allogenic transplantation is worth considering to treat this disease. Methods: We performed allogeneic in utero transplantation of GFP-positive myoblasts and adipose-derived mesenchymal stem cells into murine DMD model animals. The transplantation route in this study was fetal intraperitoneal transplantation and transplacental transplantation...

Mice with severe combined immunodeficiency are commonly used as hosts of human cells. Size, longevity, and physiology, however, limit the extent to which immunodeficient mice can model human systems. To address these limitations, we generated RAG2 -/- IL2RG y /- immunodeficient pigs and demonstrate successful engraftment of SLA mismatched allogeneic D42 fetal liver cells, tagged with pH2B-eGFP, and human CD34+ hematopoietic stem cells after in utero cell transplantation. Following intrauterine injection at day 42-45 of gestation, fetuses were allowed to gestate to term and analyzed postnatally for the presence of pig (allogeneic) and human (xenogeneic) B cells, T -cells and NK cells in peripheral blood and other lymphoid tissues...

Background: Kidney disease is a major public health issue arising from loss of glomerular podocyte function, and there are considerable sex differences in its prognosis. Evidence suggests a renoprotective effect of estrogen and soy diet-derived phytoestrogens, although the molecular basis for this is poorly understood. Objective: Here, we aim to assess sex differences in expression of key proteins associated with podocyte survival and determine the effects of dietary soy on glomerular and podocyte signaling...

Introduction The advent of novel fetal interventions has increased interest in fetal intervention for previously "lethal" anomalies such as bilateral renal agenesis or other congenital anomalies of the kidney and urinary tract (CAKUT) associated with in utero renal failure. While there have been rare reports of successful births following intervention in these cases, there is a paucity of data regarding the risks, benefits, and outcomes of intervention. To address this gap, this study presents our experience with fetal intervention for anatomic or functional renal agenesis...

In utero hematopoietic cell transplantation (IUHCT) is considered a potentially efficient therapeutic approach with relatively few side effects, compared to adult hematopoietic cell transplantation, for various hematological genetic disorders. The principle of IUHCT has been extensively studied in rodent models and in some large animals with close evolutionary similarities to human beings. However, IUHCT has only been used to rebuild human T cell immunity in certain patients with inherent immunodeficiencies...

Research in the Department of Radiobiology at the Institute for Environmental Sciences (IES) has focused mainly on the biological effects of long-term low dose-rate radiation exposure on mice since its establishment 30 y ago. The IES has exposed thousands of mice of various strains, to gamma-rays, mostly chronically, at low dose-rates of 0.05, 1, 20 or 100 mGy/d, at medium dose-rates of 200 or 400 mGy/d or at acute high dose-rates of 0.7-0.9 Gy/min. The dose-rate 0.05 mGy/d is comparable with the dose limit for radiation workers of 100 mSv/5 y...

OBJECTIVE: Coronary artery abnormalities (CA) occur in patients with hypoplastic left heart syndrome (HLHS) and may be associated with higher mortality and heart transplantation (HT). We aimed to determine whether fetuses with HLHS and prenatal CA have a higher risk of death or HT. METHODS: We performed a retrospective review of fetal echocardiograms with HLHS from 2011 to 2018. We excluded fetuses with ventricular septal defects, elective termination, death in utero, planned postnatal non-intervention, or absent follow-up data...

A male infant born at 34 weeks' gestation presented with acute cardiorespiratory decompensation soon after birth followed by renal failure. Initial clinical course was complicated by ventilator requirement, bilateral pneumothoraces, and hypotension managed with multiple inotropes. Persistent renal failure with oliguria and renal ultrasound showing noncystic medical renal disease prompted further investigation. Whole-exome sequencing showed 2 pathologic mutations in the angiotensin-converting enzyme (ACE) gene, suggesting a diagnosis of renal tubular dysgenesis (RTD)...

Maternal obesity and consumption of a high-fat diet significantly elevate risk for pediatric nonalcoholic fatty liver disease (NAFLD), affecting 10% of children in the US. Almost half of these children are diagnosed with nonalcoholic steatohepatitis (NASH), a leading etiology for liver transplant. Animal models show that signs of liver injury and perturbed lipid metabolism associated with NAFLD begin in utero; however, safe dietary therapeutics to blunt developmental programming of NAFLD are unavailable. Using a mouse model of maternal Western-style diet (WD), we previously showed that pyrroloquinoline quinone (PQQ), a potent dietary antioxidant, protected offspring of WD-fed dams from development of NAFLD and NASH...

Gestational alloimmune liver disease resulting in neonatal haemochromatosis is a rare but often lethal neonatal and fetal condition and is the leading cause of fetal and neonatal liver injury. Chelation-antioxidant treatment, intravenous immunoglobulin therapy and exchange transfusions, as well as liver transplantation have been used as treatments for the affected newborn at birth. In the reported case, a woman with previous neonatal death at 34 weeks of gestation due to gestational alloimmune liver disease commenced weekly doses of intravenous immunoglobulin (1 mg/kg) from 15 weeks in a subsequent pregnancy...

Cytomegalovirus (CMV) is a common herpesvirus that establishes lifelong latent infections and interacts extensively with the host immune system, potentially contributing to immune activation and inflammation. Given its proclivity for infecting the brain and its reactivation by inflammatory stimuli, CMV is well known for causing central nervous system complications in the immune-naïve (e.g., in utero) and in the immunocompromised (e.g., in neonates, individuals receiving transplants or cancer chemotherapy, or people living with HIV)...

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It represents a spectrum of disease from simple hepatic steatosis to steatohepatitis that may develop into progressive hepatic fibrosis and even cirrhosis. NAFLD is the most rapidly increasing indication for liver transplantation in adults. In children, the incidence of NAFLD has also increased over the past decade. Although the majority of children with NAFLD are overweight or obese, there is an increasing subset of children with normal body mass index with so-called lean NAFLD...