In vivo modeling of human neuron dynamics and Down syndrome

Harnessing the potential of human stem cells for modeling the physiology and diseases of cortical circuitry requires monitoring cellular dynamics in vivo. We show that human induced pluripotent stem cell (iPSC)–derived cortical neurons transplanted into the adult mouse cortex consistently organized into large (up to ~100 mm3) vascularized neuron-glia territories with complex cytoarchitecture. Longitudinal imaging of>4000 grafted developing human neurons revealed that neuronal arbors refined via branch-specific retraction; human synaptic networks substantially restructured over 4 months, with balanced rates of synapse formation and elimination; and oscillatory population activity mirrored the patterns of fetal neural networks. Lastly, we found increased synaptic stability and reduced oscillations in transplants from two individuals with Down syndrome, demonstrating the potential of in vivo imaging in human tissue grafts for patient-specific modeling of cortical development, physiology, and pathogenesis.
Source: ScienceNOW - Category: Science Authors: Tags: Neuroscience, Online Only r-articles Source Type: news

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In conclusion, we have shown the safety and efficacy of Vemurafenib in a pediatric patient with DS affected by PXA. Ethics Statement This study was carried out in accordance with the recommendations of the Internal Review Board of the Bambino Gesù Children's Hospital with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Internal Review Board of the Bambino Gesù Children's Hospital. Informed Consent The authors declare that written informed consent was obtained from the pat...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Children with Down syndrome (DS) carry a 20-fold higher risk of developing acute lymphoblastic leukemia (ALL) than other children and have increased rates of treatment-related mortality (TRM) and relapse. The prognosis for relapsed DS-ALL patients is grim with long-term survival rates of 20%. Blinatumomab, a CD19/CD3 bispecific antibody, is FDA approved for relapsed pediatric pre-B ALL, and recently approved for patients with minimal residual disease (MRD). However there are few reports of the use of blinatumomab in DS-ALL patients, and no reports of blinatumomab as a bridge to stem cell transplant (SCT) in this population.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 494 Source Type: research
When Noah Shulman was born a few days after Christmas 2016, his parents Kristelle and Evan had no reason to worry about him. The pregnancy went smoothly, and so did the birth. But within a few days of taking his first breath, Noah began to struggle. He wasn’t feeding, so he started losing weight. He was also lethargic. Several pediatricians reassured the Shulmans that they were probably just overly sensitive to Noah’s symptoms because Kristelle is a nurse and Evan is a physician assistant–a case of first-time-parent-white-coat syndrome. “They kind of dismissed us as neurotic parents,” says Eva...
Source: TIME: Science - Category: Science Authors: Tags: Uncategorized fertility Research Source Type: news
IntroductionDespite a high cure rate for pediatric ALL, the prognosis for pts who suffer from r/r disease remains poor. Pediatric pts with r/r ALL face multiple lines of therapy, acute and long-term treatment toxicities, and have limited survival. New agents that are able to provide durable disease control and long-term survival with limited toxicity are needed. Blinatumomab (blin) is a bispecific T-cell engaging (BiTE®) antibody construct that redirects CD3+ cytotoxic T cells to lyse CD19+ B cells. We evaluated the safety and efficacy of blin in pediatric pts with B-cell precursor r/r ALL enrolled in an expanded acces...
Source: Blood - Category: Hematology Authors: Tags: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Poster I Source Type: research
We present our methods, validated at two large freestanding children's hospitals, and incidence estimates of relapse or HSCT as first events in a national cohort.The Pediatric Health Information System (PHIS) cohort included patients aged 0-21 admitted between 1/1/2004 and 12/13/2013, previously identified with de novo ALL. We reviewed daily inpatient pharmacy, diagnosis, and procedure codes for patients in the PHIS ALL cohort from the Children's Hospital of Philadelphia (CHOP; 2004-2013) and Texas Children's Hospital (TCH; 2007-2013). Events were captured until the first of 5 years from diagnosis or last day of PHIS data....
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Outcomes in Lymphoid Malignancies and Stem Cell Transplant Source Type: research
ConclusionThe most recent DCOG protocol was associated with the highest incidence of BSIs, probably as a result of the high intensity of this protocol. Furthermore, the use of prophylactic antibiotics with gram-negative coverage may have resulted in a relatively higher incidence in gram-positive BSI. The high incidence stresses the urge to improve anti-infective supportive care measures.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 613. Acute Myeloid Leukemia: Clinical Studies: Poster II Source Type: research
Conclusions: We demonstrate in our population-based cohort of heavily pre-treated and high-risk patients that initial low-intensity chemotherapy had a very high likelihood of successfully bridging children to CAR-T infusion. Low-intensity bridging regimens were associated with lower rates of toxicity and higher quality of life as indicated by fewer inpatient days. Low-intensity regimens should be considered the first line option in this population.DisclosuresGrupp: Jazz Pharmaceuticals: Consultancy; Adaptimmune: Consultancy; University of Pennsylvania: Patents &Royalties; Novartis Pharmaceuticals Corporation: Consultan...
Source: Blood - Category: Hematology Authors: Tags: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Poster I Source Type: research
INTRODUCTIONSevere combined immunodeficiency disease (SCID) is the most severe form of primary immunodeficiency disorders (PIDs). Impaired cellular and humoral immunity renders the affected infants susceptible to various infections and results in death within the first 2 years of life. Affected infants are asymptomatic at birth, untreated disease leads to death, and prompt treatment (i.e., hematopoietic stem cell transplantation, gene therapy, or enzyme replacement therapy) is linked to significant improvement in outcome. Thus, SCID meets the disease criteria for newborn screening (NBS). The T-cell receptor excision circle...
Source: Blood - Category: Hematology Authors: Tags: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Poster III Source Type: research
FLT3/ITD mutations occur in approximately 15%-25% of AML in children and young adults and can be amenable to targeting with FLT3 inhibitors. We have demonstrated that those with high ITD allelic ratio (AR) have an adverse prognosis, which can be ameliorated in part by hematopoietic stem cell transplant (HSCT) in CR1. However, even with aggressive therapy only a subset FLT3/ITD (ITD+) patients are cured, suggesting that within this cohort there exists heterogeneity among responses to therapy and overall outcomes. As next generation sequencing has illuminated the distinct and complex genomic profiles of pediatric AML, we hyp...
Source: Blood - Category: Hematology Authors: Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis III Source Type: research
The hallmark of hematopoietic stem cells (HSCs) is their ability to self-renew and differentiate into multiple blood cell types. Transplantation of human HSCs into immunocompromised mice is the gold standard for evaluating functionality and has been adapted to study leukemia initiating cells (LICs). However, specific cellular subsets do not survive post-xenotransplantation, due to a dependence on factors that may be missing in a non-primate microenvironment.We have been optimizing the zebrafish as a xenograft platform. We created novel zebrafish that express human stem cell factor (SCF/KITLG), granulocyte-macrophage colony...
Source: Blood - Category: Hematology Authors: Tags: 506. Hematopoiesis and Stem Cells: Microenvironment, Cell Adhesion, and Stromal Stem Cells: Poster I Source Type: research
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