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Objective: To investigate the maternal and fetal safety of In utero stem cell transplantation (IUSCT). Methods: Medline®, Embase and Cochrane library (1967−2023) search for publications reporting IUSCT in humans. Two reviewers independently screened abstracts and full‐text papers. Results: Sixty six transplantation procedures in 52 fetuses were performed for haemoglobinopathies (n = 14), red cell/bleeding disorders (n = 4), immunodeficiencies (n = 15), storage disorders (n = 7), osteogenesis imperfecta (n = 2) and healthy fetuses (n = 10). The average gestational age was 18.9 weeks; of procedures reporting the injection route, cells were delivered by intraperitoneal (n = 37), intravenous (n = 19), or intracardiac (n = 4) injection or a combination (n = 3); most fetuses received one injection (n = 41). Haematopoietic (n = 40) or mesenchymal (n = 12) stem cells were delivered. The cell dose was inconsistently reported (range 1.8−3.3 × 109 cells total (n = 27); 2.7−5.0 × 109/kg estimated fetal weight (n = 17)). The acute fetal procedural complication rate was 4.5% (3/66); the acute fetal mortality rate was 3.0% (2/66). Neonatal survival was 69.2% (36/52). Immediate maternal and pregnancy outcomes were reported in only 30.8% (16/52) and 44.2% (23/52) of cases respectively. Four fetal/pregnancy outcomes would also classify as ≥ Grade 2 maternal adverse events. Conclusions: Short‐, medium‐, and long‐term maternal and fetal adverse events should be reported in all IUSCT studies. Key points: What is already known about this topic?Fetal therapy, such as fetal blood transfusion, is commonly used to treat fetal anemia with a good fetal safety profile. Certain genetic disorders such as Osteogenesis Imperfecta (OI) and α thalassaemia major are commonly diagnosed prenatally. These diseases may be amenable to treatment by In utero stem cell transplantation (IUSCT). Clinical trials will require an understanding of the safety of IUSCT for both mother and fetus. What does this study add? (67 words)This systematic review found that the acute fetal complication rate of IUSCT was 4.5% per procedure. Fetal outcomes were commonly the focus of publications. Maternal adverse events and pregnancy outcomes have been poorly reported. As fetal therapeutic procedures must balance maternal and fetal risk/benefit, we recommend that studies of in utero cell transplantation report not only on efficacy but also maternal and fetal adverse events. [ABSTRACT FROM AUTHOR]

Introduction Bipolar disorder is characterized by recurrent episodes of manic or depressive mood interspaced with periods of euthymia. The underlying pathophysiology of the disease is poorly understood, although manic symptoms [...], Background: In recent years, a role for the immune system in the pathogenesis of psychiatric diseases has gained increased attention. Although bipolar disorder appears to be associated with altered serum cytokine levels, a putative immunological contribution to its pathophysiology remains to be established. Hitherto, no direct analyses of cerebrospinal fluid (CSF) cytokines in patients with bipolar disorder have been performed. Methods: We analyzed CSF cytokine concentrations in euthymic patients with diagnosed bipolar disorder type I (n = 15) or type II (n = 15) and healthy volunteers (n = 30) using an immunoassay-based protein array multiplex system. Results: The mean interleukin (IL)-1β level (4.2 pg/mL, standard error of the mean [SEM] 0.5) was higher and the IL-6 level (1.5 pg/mL, SEM 0.2) was lower in euthymic bipolar patients than in healthy volunteers (0.8 pg/mL, SEM 0.04, and 2.6 pg/mL, SEM 0.2, respectively). Patients with 1 or more manic/hypomanic episodes during the last year showed significantly higher levels of IL-1β (6.2 pg/mL, SEM 0.8; n = 9) than patients without a recent manic/hypomanic episode (3.1 pg/mL, SEM 1.0; n = 10). Limitations: All patients were in an euthymic state at the time of sampling. Owing to the large variety of drugs prescribed to patients in the present study, influence of medication on the cytokine profile cannot be ruled out. Conclusion: Our findings show an altered brain cytokine profile associated with the manifestation of recent manic/hypomanic episodes in patients with bipolar disorder. Although the causality remains to be established, these findings may suggest a pathophysiological role for IL-1β in bipolar disorder.

The role of inflammation in HIV transmission in investigated by studying the infectious and inflammatory milieu in cervical mucosa from HIV-1- and human papillomavirus (HPV)-coinfected and HPV-monoinfected women. The results have indicated the persistence of immune activation and inflammation in the genital tract of women with HPV monoinfection and in HIV-infected women coinfected with HPV.

Dendritic cells (DCs) are activated by signaling via pathogen-specific receptors or exposure to inflammatory mediators. Here we show that co-culturing DCs with apoptotic HIV-infected activated CD4+ T cells (ApoInf) or apoptotic uninfected activated CD4+ T cells (ApoAct) induced expression of co-stimulatory molecules and cytokine release. In addition, we measured a reduced HIV infection rate in DCs after co-culture with ApoAct. A prerequisite for reduced HIV infection in DCs was activation of CD4+ T cells before apoptosis induction. DCs exposed to ApoAct or ApoInf secreted MIP-1&agr;, MIP-1&bgr;, MCP-1, and TNF-&agr;; this effect was retained in the presence of exogenous HIV. The ApoAct-mediated induction of co-stimulatory CD86 molecules and reduction of HIV infection in DCs were partially abrogated after blocking TNF-&agr; using monoclonal antibodies. APOBEC3G expression in DCs was increased in co-cultures of DCs and ApoAct but not by apoptotic resting CD4+ T cells (ApoRest). Silencing of APOBEC3G in DC abrogated the HIV inhibitory effect mediated by ApoAct. Sequence analyses of an env region revealed significant induction of G-to-A hypermutations in the context of GG or GA dinucleotides in DNA isolated from DCs exposed to HIV and ApoAct. Thus, ApoAct-mediated DC maturation resulted in induction of APOBEC3G that was important for inhibition of HIV-infection in DCs. These findings underscore the complexity of differential DC responses evoked upon interaction with resting as compared with activated dying cells during HIV infection. [ABSTRACT FROM AUTHOR]