797 Wharton's jelly stem cell-derived extracellular vesicles drive neural ... OBJECTIVE: Every year, an estimated 15 million babies are born preterm. Survivors of ...
Poster Session IV
ajog.org (OR 1.5 [1.3-1.7]), and postpartum hemorrhage (OR 1.5 [1.1-2.0]). These associations remained significant after adjustment in a multivariable logistic regression model. CONCLUSION: The prevalence of concurrent cancer and pregnancy in the US increased from 2004-2013. This increase was not explained by maternal age, nor by cancer survivorship, which also increased over this interval. Pregnant women with cancer are more likely to experience medical or obstetric complications during their delivery admission.
microRNA (miRNA) content was assessed by real-time PCR. After the culture with WJ-MSC-derived EV, NPC were evaluated for the expression of markers involved in oligodendrogenic specification and differentiation by real-time PCR. RESULTS: WJ-MSC-derived EV contained miRNA that are involved in oligodendrogenic cell fate determination and differentiation (miR-338, miR-9, miR-19b, miR-138). The expression of miR-3383p and miR-219-5p, known to regulate oligodendrocyte specification and differentiation, were significantly increased in NPC after 72 h of co-culture with EV. Furthermore, the gene expression of the transcription factor neurogenic differentiation 1 (Neurod1), which blocks oligodendrogenic specification, was reduced in NPC after coculture with EV for 72 h. CONCLUSION: In conclusion, we showed that isolated WJ-MSCderived EV contained miRNA having a role in oligodendrogenesis. Furthermore, EV primed NPC towards oligodendrogenic identity, ascribing a potential neuroregenerative role to WJ-MSC-derived EV. Financial support by Gottfried and Julia Bangerter-Rhyner Foundation.
798 Intranasal administration of extracellular vesicles derived from human umbilical cord mesenchymal stem cells as a potential treatment for perinatal brain damage Gierin Thomi1,2, Marianne Joerger-Messerli1, Vale´rie Haesler1, Andreina Schoeberlein1, Daniel V. Surbek1 1
Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern and Department of Clinical Research, University of Bern, Bern, Switzerland, 2Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, Bern, Switzerland
797 Wharton’s jelly stem cell-derived extracellular vesicles drive neural progenitor cells towards oligodendroglial identity Marianne Joerger-Messerli1, Marialuigia Spinelli1, Byron Oppliger1, Gierin Thomi1,2, Vale´rie Haesler1, Martin Mueller1,3, Andreina Schoeberlein1, Daniel V. Surbek1 1
Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Switzerland and Department of Clinical Research, University of Bern, Switzerland, Bern, Switzerland, 2Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, Switzerland, Bern, Switzerland, 3Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, New Haven, CT
OBJECTIVE: Perinatal brain damage is accompanied by oligodendrocyte progenitor cell loss. The neuroregenerative effects of transplanted mesenchymal stem cells (MSC) in animal models of perinatal brain damage are presumed to rely on secreted factors such as MSC-derived extracellular vesicles (EV). Thus, the aim of this study is to evaluate the capacity of EV from human Wharton’s jelly-derived MSC (WJ-MSC) to prime neural progenitor cells (NPC) towards oligodendroglial cell fate specification. STUDY DESIGN: WJ-MSC-derived EV were isolated from culture supernatants by serial high-speed and ultracentrifugations. EV
OBJECTIVE: Every year, an estimated 15 million babies are born preterm. Survivors of preterm birth are at risk to develop severe necrotizing enterocolitis, bronchopulmonary dysplasia and perinatal brain damage. The latter is caused by cerebral hypoxia-ischemia (HI) and systemic maternal-fetal inflammation and leads to severe neurological adverse effects. A promising preclinical approach to treat perinatal brain damage is the administration of extracellular vesicles (EVs) derived from Wharton’s jelly mesenchymal stem cells (WJ-MSCs). The aim of this study is to evaluate the distribution of intranasally administered EVs in a rat model of perinatal brain damage. STUDY DESIGN: Consistent with the etiology of perinatal brain damage, 3-day old rat pups were injected with lipopolysaccharides (LPS) and subjected an unilateral carotid artery ligation followed by oxygen deprivation. EVs were isolated from WJ-MSCs culture supernatant by ultracentrifugation. EVs were labeled with an infrared fluorescent dye and delivered intranasally to the rat pups. The distribution of the EVs throughout the bodies of the pups was traced 30 min, 3h and 24h after their administration using an infrared imaging system. RESULTS: EVs were diffusely located within the pup brains already 30 min after their administration, suggesting a rapid translocation of the EVs to the brain. The accumulation of the EVs within the brain reached its peak 3 h after their administration. No more EVs were present in the brain 24 h after administration. A small fraction of the labeled EVs were also detected within the lungs and the gastrointestinal (GI) tract since the rat pups aspirate and swallow some of the EVs during the intranasal administration. No EVs were found within the spleen, indicating that the EVs do not reach the systemic circulation.
Supplement to JANUARY 2018 American Journal of Obstetrics & Gynecology
S475
Poster Session IV CONCLUSION: Intranasal delivery of EVs represents a feasible approach to treat perinatal brain damage by effectively delivering EVs to the brain while bypassing the systemic circulation. Intranasal delivery of EVs could also be suitable to treat other preterm-associated complications such as bronchopulmonary dysplasia and severe necrotizing enterocolitis as it was shown that a fraction of EVs also reached the lungs and the GI tract. Financial support by Gottfried and Julia Bangerter-Rhyner Foundation.
ajog.org Comparison of Selected Variables and Incidence of Hemorrhagic and Ischemic Strokes Variable
Hemorrhagic N=28 Ischemic N=27 P value* All Strokes N=57
Hypertension Any
17 (61)
13 (48)
Chronic Hypertension
4 (14)
4 (15)
0.347
30 (53)
Preeclampsia Syndrome
13 (46)
9 (33)
0.322
22 (39)
Vaginal Cesarean
12/28 (43)
12/21 (57)
0.322
15/28 (54)
7/21 (33)
Age (mean +/- SD)
0.159
27.4 +/- 7.18
22.1 +/- 4.43
0.0019
Delivery
Residual Deficits
12/20 (60)
14/21 (67)
0.659
26/41 (63)
Maternal Death
2 (7)
2 (7)
0.968
4 (7)
Data presented as N (%)
799 33-Year single center experience with pregnancy-associated strokes
*Comparison of hemorrhagic versus ischemic stroke
Amanda Zofkie, F. Gary Cunningham University of Texas Southwestern, Dallas, TX
OBJECTIVE: To evaluate the incidence, presentation, and causes of pregnancy-related strokes at our single-center institution in relation to timing, characterization of stroke, risk factors, pregnancy outcomes, and residual neurologic deficits in order to identify at risk patients and to improve outcomes. STUDY DESIGN: This was a retrospective observational review performed at a large county hospital. Stroke was defined as an acute neurological deficit lasting greater than 24 hours. From June 1984 through June 2017 patients were identified using three sources: medical records with ICD-9 codes for pregnancy and stroke, OB-GYN departmental database, and records of the senior author. Women were included if they suffered a stroke during pregnancy or within the 6-week puerperal period. RESULTS: During the 33-year period, 57 women were identified to have a pregnancy-associated stroke. During this same time period, there were 466,000 births at our hospital for an incidence of 12 per 100,000 deliveries. The mean patient age was 24.9 years (range 1542). We classified the strokes as hemorrhagic in 49%, ischemic in 47%, and atypical in 4%. These strokes occurred in 42% of women in the third trimester and in 36% in the puerperium. The most common presenting symptoms were headache, seizure, altered mental status, and vision changes. When hemorrhagic strokes were compared with ischemic strokes, there was a significant difference in regard to maternal age (p¼0.0019), but no significant statistical incidence of any pregnancy-associated hypertension (p¼0.347) or preeclampsia-eclampsia syndrome (p¼0.322), type of delivery (SVD p¼0.322, C-section p¼0.159), and persistence of residual neurological deficits (p¼0.659). CONCLUSION: The incidence of pregnancy-associated strokes during the 33 years of study was 12 per 100,000 births, consonant with reports from large population databases. While the distribution of hemorrhagic versus ischemic strokes was almost equal, those women with hemorrhagic strokes were more likely to be older. Overall, these women with strokes had an inordinately high incidence for any hypertension (53%) and preeclampsia syndrome (39%). Importantly, of 41 women with long term follow up, 63% had residual neurological defects.
800 Offspring of women following bariatric surgery are at an increased risk for long-term pediatric hematological morbidity Pini DAMTI1, Michael FRIGER2, Daniella LANDAU3, Eyal SHEINER4 1 Ben-Gurion University of the Negev, Beer-sheba, Israel, 2The Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Beer-sheba, Israel, 3Department of Pediatrics, Soroka University Medical Center, Ben-Gurion University of the Negev, BeerSheva, Israel., Beer-sheba, Israel, 4Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben-Gurion University of the Negev, BeerSheva, Israel., Beer-sheba, Israel
OBJECTIVE: To investigate whether offspring of women following bariatric surgery, as well as these suffering from obesity during their pregnancy, are at an increased risk for long-term pediatric hematological morbidity. STUDY DESIGN: A population based cohort study was performed comparing the risk of long-term hematological morbidity (up to the age of 18 years) of children of patients following bariatric surgery and obese women (as compared with non-obese parturients). Deliveries occurred between the years 1991-2013 in a tertiary medical center. Multiple pregnancies and fetal congenital malformations were excluded. Kaplan-Meier survival curves were constructed in order to compare cumulative hematological morbidity. Cox proportional hazards model was used to control for confounders. RESULTS: During the study period 253,808 newborns met the inclusion criteria; 961 were delivered to patients following bariatric surgery, 2473 were delivered to obese women and 250,374 were delivered to non-obese, non-post bariatric patients. Long-term total hematological morbidity was non-significantly higher in children delivered to patients following bariatric surgery (p¼0.07, Table; Log rank p¼0.07, Figure). Nevertheless, in a Cox proportional hazards model, controlling for important confounders such as maternal age, gestational age at birth, pregnant number, diabetes, hypertension, caesarian delivery, nation, smoking and low APGAR score at 5 minutes; Children delivered to women following bariatric surgery had higher rates of long term total hematological morbidity (adjusted HR¼2.12, 95% CI 1.3-3.5; P
