Transplantation with low numbers of hematopoietic stem cells (HSCs), found in many of the publically accessible cryopreserved umbilical cord blood (UCB) units, leads to delayed time to engraftment, high graft failure rates, and early mortality in many patients. A chemical screen in zebrafish identified the prostaglandin compound, 16,16 dimethyl prostaglandin E2 (dmPGE2), to be a critical regulator of hematopoietic stem cell homeostasis. We hypothesized that an ex vivo modulation with dmPGE2 prior to transplantation would lead to enhanced engraftment by increasing the effective dose of hematopoietic stem cells (HSCs) in cord blood. A phase I trial of reduced-intensity double UCB transplantation was performed to evaluate safety, rates of engraftment and fractional chimerism of dmPGE2 enhanced UCB units. To explore potential causes of the lack of enhanced efficacy in the first cohort, we characterized HSCs to determine whether the prostaglandin pathway was being activated under the ex vivo incubation conditions (4C, 10M dmPGE2, 60 minutes). Incubation conditions were identified (37C, 10M dmPGE2, 120 minutes) that maximize the activation of the prostaglandin pathway by dmPGE2 in human CD34+ cells.
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
Specimen part, Treatment
View SamplesHuman pluripotent stem cells in culture are often associated with the prime state which represents a more developed state relative to the nave state which is often associated with the inner cell mass and thought to have the potential to give rise to all cell types. We have developed a small molecule-driven cocktail FMM that maintains human pluripotent stem cells in a state similar to the naive state as defined by several properties including gene expression profile.
Platform for induction and maintenance of transgene-free hiPSCs resembling ground state pluripotent stem cells.
Specimen part
View SamplesThe undifferentiated state of pluripotent stem cells depends heavily on the culture conditions. We show that a unique combination of small molecules, SMC4, added to culture conditions converts primed pluripotent stem cells to a more nave state. By conducting Affymetix analysis we show of majority of lineage markers are repressed in SMC4 culture.
A novel platform to enable the high-throughput derivation and characterization of feeder-free human iPSCs.
Specimen part, Cell line
View SamplesUmbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the effective dose of HSCs.
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
Specimen part
View SamplesUmbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the "effective dose" of HSCs.
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
Specimen part, Treatment
View SamplesGenome-wide gene expression analysis of MyoD-infected DMD-specific iPSCs (GM05112-M5.1) on days 0 (untreated), day 3 and day 8 post Dox treatment, human primary myoblasts (undifferentiated and as differentiated myotubes), and undifferentiated iPSCs from healthy donors (iPSCs-1 and iPSCs-2).
Myogenic differentiation of muscular dystrophy-specific induced pluripotent stem cells for use in drug discovery.
Specimen part
View SamplesUmbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the effective dose of HSCs.
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
Specimen part, Treatment
View SamplesUmbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the effective dose of HSCs.
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
Specimen part
View SamplesThe analytical validation of a 15 gene prognostic signature for early-stage, completely resected, non-small-cell lung carcinoma that distinguishes between patients with good and poor prognoses.
Analytical Performance of a 15-Gene Prognostic Assay for Early-Stage Non-Small-Cell Lung Carcinoma Using RNA-Stabilized Tissue.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
RG7212 anti-TWEAK mAb inhibits tumor growth through inhibition of tumor cell proliferation and survival signaling and by enhancing the host antitumor immune response.
Sex, Specimen part, Disease, Cell line, Race, Time
View Samples