Amniotic Fluid Stem Cells for the Treatment of Surgical Disorders in the Fetus and Neonate

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146664/1/sct312346_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146664/2/sct312346.pd

Human Cardiomyocytes Prior to Birth by Integrationâ Free Reprogramming of Amniotic Fluid Cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135525/1/Supplemental_Information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135525/2/sct320165121595.pd

Thoracoscopic Repair of Recurrent Bochdalek Diaphragmatic Hernias in Children

Abstract Background: Recurrent herniation is a well-known complication following the initial repair of congenital diaphragmatic hernias (CDHs). The role of minimally invasive surgical techniques in recurrent CDH remains undefined. The purpose of this study was to evaluate our early experience with thoracoscopic repair compared with traditional open repair in children with recurrent CDH. Subjects and Methods: We retrospectively reviewed all recurrent Bochdalek CDH cases (n=24) managed at a single tertiary-care referral center between January 1990 and March 2011. Children who underwent thoracoscopic repair for recurrent CDH were identified, and their data were compared by the unpaired t test and the two-sided Fisher's exact test, as appropriate, with those of children who underwent open repair. Significance was defined as P<.05. Results: Thoracoscopic repair was attempted in 6 (25%) children with recurrent CDH. Four (67%) repairs were successfully completed without conversion to an open procedure. The mean age at thoracoscopic repair was 11.5 months (range, 8.1?16.1 months). The mean operative time was 191 minutes (range, 94?296 minutes), and all children were extubated within 24 hours. The mean hospital length of stay was 3.75 days (range, 1?6 days). There were no deaths or subsequent recurrences after a mean follow-up of 26.5 months (range, 14.3?41.3 months). There were no statistical differences in any of the measured outcome variables when compared with the open repair group. Conclusions: Our initial experience suggests that thoracoscopic repair is a feasible alternative to open repair in selected children with recurrent Bochdalek diaphragmatic hernias.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98467/1/lap%2E2012%2E0048.pd

Induced Pluripotent Stem Cells from Human Placental Chorion for Perinatal Tissue Engineering Applications

The reliable derivation of induced pluripotent stem cells (iPSCs) from a noninvasive autologous source at birth would facilitate the study of patient-specific in vitro modeling of congenital diseases and would enhance ongoing efforts aimed at developing novel cell-based treatments for a wide array of fetal and pediatric disorders. Accordingly, we have successfully generated iPSCs from human fetal chorionic somatic cells extracted from term pregnancies by ectopic expression of OCT4, SOX2, KLF4, and cMYC. The isolated parental somatic cells exhibited an immunophenotypic profile consistent with that of chorionic mesenchymal stromal cells (CMSCs). CMSC-iPSCs maintained pluripotency in feeder-free systems for more than 15 passages based on morphology, immunocytochemistry, and gene expression studies and were capable of embryoid body formation with spontaneous trilineage differentiation. CMSC-iPSCs could be selectively differentiated in vitro into various germ layer derivatives, including neural stem cells, beating cardiomyocytes, and definitive endoderm. This study demonstrates the feasibility of term placental chorion as a novel noninvasive alternative to dermal fibroblasts and cord blood for human perinatal iPSC derivation and may provide additional insights regarding the reprogramming capabilities of extra-embryonic tissues as they relate to developmental ontogeny and perinatal tissue engineering applications.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140245/1/ten.tec.2013.0480.pd

Surveillance of fetal lung lesions using the congenital pulmonary airway malformation volume ratio: natural history and outcomes

ObjectivesThe congenital pulmonary airway malformation volume ratio (CVR) is a widely used sonographic measure of relative mass size in fetuses with lung malformations. The purposes of this study were to examine serial CVR measurements to understand longitudinal growth patterns and to determine correlation with postnatal imaging.MethodsAn institutional review boardâ approved retrospective review was performed on fetuses referred for an echogenic lung malformation between 2002 and 2014. For each fetus, the CVR was prospectively calculated using 2D ultrasound and followed with advancing gestation.ResultsBased on 40 fetuses, the mean initial CVR was 0.51â ±â 0.07 at 20.5â ±â 0.3â weeks of gestation. The CVR increased after 24â weeks of gestation (pâ =â 0.0014), peaking at a CVR of 0.96â ±â 0.11 at 25.5â ±â 0.05â weeks, followed by a significant decrease in the CVR to 0.43â ±â 0.07 prior to term (pâ <â 0.0001). However, approximately one third showed no appreciable increase in size. The mean CVR was significantly correlated with postnatal chest computed tomography (CT) size dimensions (pâ =â 0.0032) and likelihood for lung resection (pâ =â 0.0055).ConclusionsFetal lung malformations tend to follow one of two distinct growth patterns, characterized by either (1) a maximal CVR between 25 and 26â weeks of gestation or (2) minimal change in relative growth. The mean CVR correlates with postnatal CT size and operative management. © 2015 John Wiley & Sons, Ltd.What’s already known about the topic?The congenital pulmonary airway malformation volume ratio (CVR) is a common prenatal ultrasound measure of relative mass size in fetuses with lung malformations.The initial CVR and maximum CVR have been shown to be predictive of hydrops and neonatal respiratory compromise, respectively.What does this study add?Gestational age is important when interpreting CVR measurements because two thirds of lesions increase in size at 25â 26â weeks before spontaneous involution occurs.The mean CVR correlates with size measured by postnatal computed tomography scan.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136421/1/pd4761_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136421/2/pd4761.pd

Human Transgene-Free Amniotic-Fluid-Derived Induced Pluripotent Stem Cells for Autologous Cell Therapy

The establishment of a reliable prenatal source of autologous, transgene-free progenitor cells has enormous potential in the development of regenerative-medicine-based therapies for infants born with devastating birth defects. Here, we show that a largely CD117-negative population of human amniotic fluid mesenchymal stromal cells (AF-MSCs) obtained from fetuses with or without prenatally diagnosed anomalies are readily abundant and have limited baseline differentiation potential when compared with bone-marrow-derived MSCs and other somatic cell types. Nonetheless, the AF-MSCs could be easily reprogrammed into induced pluripotent stem cells (iPSCs) using nonintegrating Sendai viral vectors encoding for OCT4, SOX2, KLF4, and cMYC. The iPSCs were virtually indistinguishable from human embryonic stem cells in multiple assays and could be used to generate a relatively homogeneous population of neural progenitors, expressing PAX6, SOX2, SOX3, Musashi-1, and PSA-NCAM, for potential use in neurologic diseases. Further, these neural progenitors showed engraftment potential in vivo and were capable of differentiating into mature neurons and astrocytes in vitro. This study demonstrates the usefulness of AF-MSCs as an excellent source for the generation of human transgene-free iPSCs ideally suited for autologous perinatal regenerative medicine applications.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140204/1/scd.2014.0110.pd

Laparoscopic double cholecystectomy for biliary dyskinesia in a child with duplicated gallbladders

Gallbladder duplication is an uncommon congenital anomaly with an estimated incidence of 1 in 4000 patients. Here we present a child who underwent a duodenal duplication cyst marsupialization who continued experiencing chronic abdominal pain one year after the initial procedure. She had an incidentally discovered duplicated gallbladder on ultrasound and an ejection fraction of 2% on hepatobiliary iminodiacetic acid (HIDA) scanning. Preoperative magnetic resonance cholangiopancreatography (MRCP) revealed two gallbladders with individual cystic ducts. She underwent an uneventful laparoscopic double cholecystectomy for biliary dyskinesia and subsequently had resolution of her chronic abdominal pain. Keywords: Duplicated gallbladder, Biliary dyskinesia, Pediatric, Cholecystectomy, Duodenal duplicatio