Faculty Bibliography

Stem cells are undifferentiated cells with the capacity for differentiation. Amniotic fluid cells (AFC) have only recently emerged as a possible source of stem cells for clinical purposes. There are no ethical or sampling constraints using amniocentesis as a standard clinical procedure for obtaining an abundant supply of AFC. AFC of human origin proliferate rapidly and are multipotent with the potential for expansion in vitro to multiple cell lines. Tissue engineering technologies using AFC are being explored. AFC may be of clinical benefit for fetal therapies, degenerative disease and regenerative medicine applications. We present a comprehensive review of the evolution of human amniotic fluid cells as a possible modality for therapeutic use.

Amniotic fluid contains a mixture of cells with capacity to differentiate into all germ layers. These cells are present in large numbers in midtrimester samples obtained for cytogenetic diagnosis, and have been identified by stem cell surface markers and transcription factors. We studied cultured samples from patients who had both direct cultures and matched cultures obtained 2 weeks later from the cytogenetics laboratory as well as patients with cytogenetics material only. Samples were cryogenically frozen, thawed, expanded in culture with excellent viability. There was considerable individual variation unrelated to gestational age or telomere length. Phenotype for embryonic markers was assessed by flow cytometry and by quantitative polymerase chain reaction. The most consistently present stem cell markers in substantial amounts were CD90, SSEA-4, & TRA-1-60. Cells with CD90, SSEA-4 & TRA-1-60 double and triple labeled also could be identified and subcultured, confirming the heterogeneity of the amniotic fluid stem cell population

Abstract Objective: The placenta of mid-gestation mice is a known rich source of hematopoietic stem cells. We hypothesized that it is also a source of other multipotent stem cells. Methods: We isolated fetal cells from the murine placenta across the second half of gestation and characterized their expression of surface antigens known to be associated with mesenchymal stem cells (MSCs) on a subset of hematopoietic lineage-negative cells. Using real-time reverse-transcriptase quantitative polymerase chain reaction, we also evaluated the expression of intracellular transcription factors (TFs) known to be associated with renal development and/or multipotent stem cells. Results: Cell phenotypes with surface marker and TF expression consistent with multipotent stem cells of a mesenchymal lineage as well as renal cell progenitors were found in the placenta. The expression of MSC and renal progenitor surface markers varied throughout gestation, but was highest on E12-15 where such cells represented a small but significant percentage of the population. Of the studied TFs, 10 of 11 renal TFs were found at moderate to high levels, and all stem cell TFs were found. Conclusion: The mid-gestation murine placenta may serve as a source of multipotent stem cells and also contains cells which may be renal cell progenitors.

Amniotic fluid stem cells(AFSC) are noncontroversial and abundant potentially transplantable cells. They are derived from fetal and amniotic sources and show osteogenic, neuronal, and adipogenic differentiation in culture. Clinical material must be expanded in culture and sorted if clinical use is desired. Cellular senescence and replicative potential for AFSC cultures has had limited study, with scant data on gene expression over time. We report changes in samples from 17 patients over multiple passages form 10 to 81 population doublings. Longevity was unrelated to telomere length in these cells. It was related to upregulation of TWIST1, which is highly expressed in stem cells, and downregulation of genes associated with apoptosis

Background: A review of the English literature from 1980 to 2010 revealed only six gravidas managed by total parenteral nutrition (TPN) for at least 16 weeks of pregnancy. We found only two gravidas with obstruction due to malrotation, both managed surgically. Case: We report a unique case of bowel obstruction presenting in the second trimester due to congenital malrotation of the small intestine that was conservatively managed by prolonged TPN, with the delivery of a healthy term baby girl. Surgical correction was delayed until the patient was not pregnant. Conclusion: Intestinal obstruction in pregnancy is rare, and malrotation of the small bowel as the cause is extremely rare. This is the first case of intestinal obstruction in midtrimester in which prolonged TPN was employed when surgery was contraindicated. TPN may be considered if surgery cannot be performed, with an excellent outcome likely

If maternal atopy and environmental exposure affect prenatal Th cell development, the maternal and fetal immune systems should display common Th1/Th2 phenotypes. To test this hypothesis, we studied maternal and neonatal blood samples from mothers with total serum IgE <300 IU/mL. Basal levels of IFN-gamma, IL-4, and eotaxin in paired maternal and fetal sera were tightly correlated. Polyclonal T cell activation in vitro by Staphylococcal exotoxin B induced co-ordinate IFN-gamma production from paired maternal and fetal mononuclear cells, accompanied by co-ordinate increases in activated CD4+CD69+ cells that display the CCR4+Th2 and CXCR3+ Th1 phenotypes. Maternal and fetal CD4+CXCR3+ T cells were subsequently identified as the major producers of IFN-gamma. The data established that a transplacental nexus exists during normal pregnancy and that fetal Th cell responses may be biased by the maternal immune system.