Novel window on early human neurodevelopment via fetal exosomes in maternal blood

Abstract

Adverse in utero exposures can disrupt fetal brain development, deplete subpopulations of neurons and inhibit formation of normal synaptic connections. A major roadblock to unraveling the precise mechanisms and timing of human neurodevelopmental derangement is the almost complete absence of sensitive noninvasive assessments. We present novel methods for isolating fetal neuronal exosomes from maternal plasma as a noninvasive platform for testing aspects of fetal neurodevelopment as early as the 1st trimester. Our methodology represents an important breakthrough both in understanding mechanisms of injury in vivo in a human system and potentially for monitoring clinical interventions seeking to promote fetal brain health.

Placenta-derived exosomes: potential biomarkers of preeclampsia

“…98 Although these exosomal membrane-bound proteins are associated with pregnancy, they cannot be used as definitive markers of placenta-derived exosomes, due to their lack of placental specificity; therefore, placental ALP remains the marker of choice when isolating and identifying placenta-derived exosomes. [79][80][81]85,90,99,100 Even though it is known that exosomes contain mRNA and miRNA, which are key molecular mediators in translational and posttranscriptional modification, the exact composition of these exosomal constituents has not been elucidated in placenta-derived exosomes. Therefore, future studies should incorporate identification of novel nucleic acid sequences in placenta-derived exosomes in normal and PE pregnancies to enhance the specificity and sensitivity of these vesicles as biomarkers of PE.…”

Novel biomarkers to assess in utero effects of maternal opioid use: First steps toward understanding short‐ and long‐term neurodevelopmental sequelae

“…[9][10][11][12] Currently, it is not possible to predict which opioid-exposed newborns will require pharmacotherapy for NAS. 22 Our published findings show that purified FCEs can be used to detect fetal CNS damage caused by in utero alcohol exposure, hypoxia and viral infection. Opioid dose is a poor predictor 13 ; some factors that have been associated with NAS severity include: cooccurring exposure to benzodiazepines, 14,15 anti-depressants, 16,17 marijuana use or heavy smoking, 18,19 as well as genetic factors.…”

“…22 Briefly, total ECVs were prepared from maternal plasma (EXOQ; System Biosciences, Inc., Mountainview, California). 22 Briefly, total ECVs were prepared from maternal plasma (EXOQ; System Biosciences, Inc., Mountainview, California).…”

“…Between 47% and 81% of newborns with gestational methadone or buprenorphine exposure will require pharmacotherapy. 22,23 Thus FCEs could be a new tool to interrogate in vivo neurodevelopment involving elements of opioid signaling pathways, including proteins (mu-opioid receptor [μOR], cannabinoid receptors) and microRNAs (miRNAs). 20,21 None of these factors are sufficient to reliably predict NAS severity, and the mechanisms by which they impact NAS are not well understood.…”

Stem Cell Therapy in Pediatric Neurological Disabilities

“…In animal models, these cells have shown to produce the deficient proteins and make new muscle cells which fuse with the host fibers. Further, stem cell-derived exosomes which are small membrane vesicles and are responsible for inter-cellular communication, promote muscle regeneration by enhancing myogenesis and angiogenesis [74]. Physical Disabilities -Therapeutic Implications We conducted a study on 150 patients diagnosed with muscular dystrophy.…”