The Effect of Scaffold Modulus on the Morphology and Remodeling of Fetal Mesenchymal Stem Cells

Hydrogel materials have been successfully used as matrices to explore the role of biophysical and biochemical stimuli in directing stem cell behavior. Here, we present our findings on the role of modulus in guiding bone marrow fetal mesenchymal stem cell (BMfMSC) fate determination using semi-synthetic hydrogels made from PEG-fibrinogen (PF). The BMfMSCs were cultivated in the PF for up to 2 weeks to study the influence of matrix modulus (i.e., cross-linking density of the PF) on BMfMSC survival, morphology and integrin expression. Both two-dimensional (2D) and three-dimensional (3D) culture conditions were employed to examine the BMfMSCs as single cells or as cell spheroids. The hydrogel modulus affected the rate of BMfMSC metabolic activity, the integrin expression levels and the cell morphology, both as single cells and as spheroids. The cell seeding density was also found to be an important parameter of the system in that high densities were favorable in facilitating more cell-to-cell contacts that favored higher metabolic activity. Our findings provide important insight about design of a hydrogel scaffold that can be used to optimize the biological response of BMfMSCs for various tissue engineering applications

Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2.

During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells, substances from ingested amniotic fluid, food antigens, and microbes. Yet the capacity of the fetal immune system, including antigen-presenting cells, to detect and respond to such stimuli remains unclear. In particular, dendritic cells, which are crucial for effective immunity and tolerance, remain poorly characterized in the developing fetus. Here we show that subsets of antigen-presenting cells can be identified in fetal tissues and are related to adult populations of antigen-presenting cells. Similar to adult dendritic cells, fetal dendritic cells migrate to lymph nodes and respond to toll-like receptor ligation; however, they differ markedly in their response to allogeneic antigens, strongly promoting regulatory T-cell induction and inhibiting T-cell tumour-necrosis factor-α production through arginase-2 activity. Our results reveal a previously unappreciated role of dendritic cells within the developing fetus and indicate that they mediate homeostatic immune-suppressive responses during gestation

SAFETY AND EFFICACY OF ADENO-ASSOCIATED VIRAL VECTOR MEDIATED INTRAUTERINE GENE THERAPY FOLLOWING EARLY- AND LATE-GESTATION INTERVENTION IN A NON-HUMAN PRIMATE MODEL

2nd International Conference on In Utero Transplantation and Fetal Gene Therapy (iFETIS

INTRAUTERINE GENE THERAPY IN A NON-HUMAN PRIMATE MODEL

Ph.DDOCTOR OF PHILOSOPH

Early Versus Late Gestation Approaches in Fetal Gene Therapy

American Society of Gene and Cell TherapyUnited State

Human Fetal Hearts with Tetralogy of Fallot has Altered Fluid Mechanical Force Environment from Normal Fetal Hearts

International Fetal Medicine and Surgery Societ

Intrauterine gene transfer at early gestation with safe postnatal vector re-administration: a therapeutic strategy for early-onset congenital disease

American Society of Gene and Cell Therap

MOTORIZING AND OPTIMIZING ULTRASOUND STRAIN ELASTOGRAPHY FOR DETECTING INTRAUTERINE GROWTH RESTRICTION PREGNANCIES

International Fetal Medicine and Surgery Societ

Postnatal transplantion to boost chimerism following intrauterine haematopoietic cell transplantation (IUHCT) in a murine model of thalassemia

British Society for Gene and Cell Therapy AnnualConference and Joint UK RegenerativeMedicine Platform MeetingUnited Kingdo

A SHORT INVESTIGATION OF MIXED HAEMATOPOIETIC CHIMERISM: AN NHP MODEL OF INTRAUTERINE HAEMATOPOIETIC STEM CELL TRANSPLANTATION (IUHSCT)

American Society of Gene & Cell TherapyUnited State