Fetal lung underdevelopment is rescued by administration of amniotic fluid stem cell extracellular vesicles in rodents

Fetal lung underdevelopment, also known as pulmonary hypoplasia, is characterized by decreased lung growth and maturation. The most common birth defect found in babies with pulmonary hypoplasia is congenital diaphragmatic hernia (CDH). Despite research and clinical advances, babies with CDH still have high morbidity and mortality rates, which are directly related to the severity of lung underdevelopment. To date, there is no effective treatment that promotes fetal lung growth and maturation. Here, we describe a stem cell–based approach in rodents that enhances fetal lung development via the administration of extracellular vesicles (EVs) derived from amniotic fluid stem cells (AFSCs). Using fetal rodent models of pulmonary hypoplasia (primary epithelial cells, organoids, explants, and in vivo), we demonstrated that AFSC-EV administration promoted branching morphogenesis and alveolarization, rescued tissue homeostasis, and stimulated epithelial cell and fibroblast differentiation. We confirmed this regenerative ability in in vitro models of lung injury using human material, where human AFSC-EVs obtained following good manufacturing practices restored pulmonary epithelial homeostasis. Investigating EV mechanism of action, we found that AFSC-EV beneficial effects were exerted via the release of RNA cargo. MicroRNAs regulating the expression of genes involved in lung development, such as the miR17–92 cluster and its paralogs, were highly enriched in AFSC-EVs and were increased in AFSC-EV–treated primary lung epithelial cells compared to untreated cells. Our findings suggest that AFSC-EVs hold regenerative ability for underdeveloped fetal lungs, demonstrating potential for therapeutic application in patients with pulmonary hypoplasia

Sexual Mixing Patterns and Partner Characteristics of Black MSM in Massachusetts at Increased Risk for HIV Infection and Transmission

Black men who have sex with men (MSM) are at increased risk for HIV infection in the United States compared to other MSM. The aim of this study was to investigate Black MSM’s sexual mixing patterns and partner characteristics in relation to sexual risk taking, as a possible explanation for this observed increase in HIV incidence. Between January and July 2008, 197 Black MSM were recruited via modified respondent-driven sampling and completed optional pretest and post-test HIV serological testing, counseling, and a demographic, behavioral, and psychosocial assessment battery. Bivariate and multivariable logistic regression procedures were used to examine predictors of risky sex across partner types. Overall, 18% of the sample was HIV-infected; 50% reported unprotected intercourse with men, 30% with women, and 5% with transgender partners. Fifty-three percent identified as bisexual or straight, although all reported oral or anal sex with another man in the prior 12 months. Significant predictors of engaging in at least one episode of: (1) serodiscordant unprotected anal sex (UAS) with a male partner in the past 12 months: individuals at risk for social isolation (AOR = 4.23; p = 0.03), those with unstable housing (AOR = 4.19; p = 0.03), and those who used poppers at least weekly during sex (AOR = 5.90; p = 0.05); (2) UAS and/or unprotected vaginal intercourse with a female partner in the past 12 months: those with unstable housing (AOR = 4.85; p = 0.04), those who used cocaine at least weekly during sex (AOR = 16.78; p = 0.006), being HIV-infected (AOR = 0.07; p = 0.02), and feeling social norms favor condom use (AOR = 0.60; p = 0.05); (3) UAS with the participants’ most recent nonmain male sex partner: use of alcohol and drugs during last sex by participant (AOR = 4.04; p = 0.01), having sex with a Hispanic/Latino male (AOR = 2.71; p = 0.04) or a Black male (AOR = 0.50; p = 0.05) compared to a White male, and lower education (AOR = 1.31; p = 0.02). Findings suggest that sexual risk behaviors of Black MSM differ across partner type and by the characteristics of their sexual networks and that this subpopulation of MSM are at high risk for HIV acquisition and transmission. Effective prevention strategies need to address the distinct sexual and behavioral risk patterns presented by different sexual partnerships reported by Black MSM