Other

Children's Medical Center Corporation

The General Hospital Corporation

Sanford-burnham Medical Research Institute

Northeastern Ohio University

Biotime, Inc.

Mandala Biosciences, LLC

Evan Y Snyder

John H Wolfe

Seung U Kim

Xandra O Breakefield

Karen S Aboody

Michael D West

Ulrich Herrlinger

William P Lynch

David Larocca

Dana Larocca

Paola A Bignone

Paola Bignone

Rodolfo Gonzalez

Alice B Brown

Seth P Finkelstein

The invention provides methods, compositions and kits for the identification and enrichment of progenitor cell lines obtained from pluripotent stem cells.

Methods and compositions for targeting progenitor cell lines

We have identified ZNF206, a novel repressor of human embryonic stem cell (hESC) differentiation. Repressing extra-embryonic endoderm development preserves the pluripotent state of human embryonic stem cells, and, conversely downregulating expression of ZNF206 in hESCs causes them to upregulate the expression of genes associated with the extra-embryonic endodermal lineage, down-regulate genes associated with the pluripotent state, and may lead to the further emergence of genes associated with even more differentiated lineages and phenotypes.

ZNF206: regulator of embryonic stem cell self-renewal and pluripotency

The present invention is based upon a surprising finding that stem cells, more particularly neural stem cells, can migrate throughout a brain tumor and track metastatic brain tumor cells. The invention provides a method for treating brain tumors by administering genetically engineered neural stem cells in an individual affected by brain tumors. The invention also provides a method of preparing genetically engineered neural stem cells and a composition comprising genetically engineered neural stem cells in a pharmaceutically acceptable carrier.

Neural stem cells and use thereof for brain tumor therapy

The present invention relates to the field of cellular and molecular therapy with modified (genetically or growth factor engineered) and unmodified stem cells (SCs). More particularly, the invention relates to a method of systemic treatment of central nervous system (CNS) and other tumors in both intracranial/intraspinal and extracranial/extraspinal sites, using neural stem cells (NSCs), a prototype for solid organ, non-hematopoietic stem cells.

Systemic gene delivery vehicles for the treatment of tumors

The present application relates to methods, kits and compositions for improving a subject's recovery from CNS injury. In certain aspects, methods of the invention comprise administering to a subject cells and a neural stimulant. Recovery may be manifest by improvements in sensorimotor or cognitive abilities, e.g., improved limb movement and control or improved speech capability. In certain embodiments, subject methods can be used as part of a treatment for damage resulting from ischemia, hypoxia or trauma.

Methods, compositions and kits for promoting recovery from damage to the central nervous system

Stable clones of neural stem cells (NSCs) have been isolated from the human fetal telencephalon. In vitro, these self-renewing clones (affirmed by retroviral insertion site) can spontaneously give rise to all 3 fundamental neural cell types (neurons, oligodendrocytes, astrocytes). Following transplantation into germinal zones of the developing newborn mouse brain, they, like their rodent counterparts, can participate in aspects of normal development, including migration along well-established migratory pathways to disseminated CNS regions, differentiation into multiple developmentally- and regionally-appropriate cell types in response to microenvironmental cues, and non-disruptive, non-tumorigenic interspersion with host progenitors and their progeny. Readily genetically engineered prior to transplantation, human NSCs are capable of expressing foreign transgenes in vivo in these disseminated locations. Further supporting their potential for gene therapeutic applications, the secretory products from these NSCs can cross-correct a prototypical genetic metabolic defect in abnormal neurons and glia in vitro as effectively as do murine NSCs. Finally, human cells appear capable of replacing specific deficient neuronal populations in a mouse model of neurodegeneration and impaired development, much as murine NSCs could. Human NSCs may be propagated by a variety of means&mdash;both epigenetic (e.g., chronic mitogen exposure) and genetic (transduction of the propagating gene vmyc)&mdash;that are comparably safe (vmyc is constitutively downregulated by normal developmental mechanisms and environmental cues) and effective in yielding engraftable, migratory clones, suggesting that investigators may choose the propagation technique that best serves the demands of a particular research or clinical problem. All clones can be cryopreserved and transplanted into multiple hosts in multiple settings.

Engraftable human neural stem cells

Stable clones of neural stem cells (NSCs) have been isolated from the human fetal telencephalon. In vitro, these self-renewing clones (affirmed by retroviral insertion site) can spontaneously give rise to all 3 fundamental neural cell types (neurons, oligodendrocytes, astrocytes). Following transplantation into germinal zones of the developing newborn mouse brain, they, like their rodent counterparts, can participate in aspects of normal development, including migration along well-established migratory pathways to disseminated CNS regions, differentiation into multiple developmentally- and regionally-appropriate cell types in response to microenvironmental cues, and non-disruptive, non-tumorigenic interspersion with host progenitors and their progeny. Readily genetically engineered prior to transplantation, human NSCs are capable of expressing foreign transgenes in vivo in these disseminated locations. Further supporting their potential for gene therapeutic applications, the secretory products from these NSCs can cross-correct a prototypical genetic metabolic defect in abnormal neurons and glia in vitro as effectively as do murine NSCs. Finally, human cells appear capable of replacing specific deficient neuronal populations in a mouse model of neurodegeneration and impaired development, much as murine NSCs could. Human NSCs may be propagated by a variety of means&mdash;both epigenetic (e.g., chronic mitogen exposure) and genetic (transduction of the propagating gene vmyc)&mdash;that are comparably safe (vmyc is constitutively downregulated by normal developmental mechanisms and environmental cues) and effective in yielding engraftable, migratory clones, suggesting that investigators may choose the propagation technique that best serves the demands of a particular research or clinical problem All clones can be cryopreserved and transplanted into multiple hosts in multiple settings.

Stable clones of neural stem cells (NSCs) have been isolated from the human fetal telencephalon. In vitro, these self-renewing clones (affirmed by retroviral insertion site) can spontaneously give rise to all 3 fundamental neural cell types (neurons, oligodendrocytes, astrocytes). Following transplantation into germinal zones of the developing newborn mouse brain, they, like their rodent counterparts, can participate in aspects of normal development, including migration along well-established migratory pathways to disseminated CNS regions, differentiation into multiple developmentally- and regionally-appropriate cell types in response to microenvironmental cues, and non-disruptive, non-tumorigenic interspersion with host progenitors and their progeny. Readily genetically engineered prior to transplantation, human NSCs are capable of expressing foreign transgenes in vivo in these disseminated locations. Further supporting their potential for gene therapeutic applications, the secretory products from these NSCs can cross-correct a prototypical genetic metabolic defect in abnormal neurons and glia in vitro as effectively as do murine NSCs. Finally, human cells appear capable of replacing specific deficient neuronal populations in a mouse model of neurodegeneration and impaired development, much as murine NSCs could. Human NSCs may be propagated by a variety of means--both epigenetic (e.g., chronic mitogen exposure) and genetic (transduction of the propagating gene vmyc)--that are comparably safe (vmyc is constitutively downregulated by normal developmental mechanisms and environmental cues) and effective in yielding engraftable, migratory clones, suggesting that investigators may choose the propagation technique that best serves the demands of a particular research or clinical problem. All clones can be cryopreserved and transplanted into multiple hosts in multiple settings.

Growing community of inventors

Jamaica Plain, MA, United States of America

Evan Y Snyder