Neuro Spheres Holdings Ltd.

Neurotech S.a.

Cytotherapeutics, Inc.

Modex Therapeutiques, S.a.

Neurospheres, Ltd.

E Edward Baetge

Joseph P Hammang

Samuel Weiss

Brent A Reynolds

Peter D Spear

Weng Tao

William F Hickey

Shou Wong

William G Tsiarias

Thomas Hunziker

Alain Limat

Vincent Ronfard

William G Tsiaras

This invention provides compositions, such as capsules, comprising transformed cells that express immunostimulatory cell surface polypeptides which are expressed on the cell surface and are capable of stimulating an immune response against the cell in a host.

Cell surface molecule-induced macrophage activation

The invention discloses methods of proliferation and differentiation of multipotent neural stem cells. Also provided are methods of making cDNA libraries and methods of screening biological agents which affect proliferation differentiation survival phenotype or function of CNS cells.

Methods of proliferating undifferentiated neural cells

Methods of screening biological agents

The present invention provides the use and composition of matter of angiogenic or other growth factors expressed by combining various types and stages of differentiation of allogeneic human cell strains or lines in unencapsulated pastes (mixed with or applied to extracellular matrix material or synthetic biocompatible substances) to be temporarily applied to wounds or defects in the skin or other tissues for the restoration of blood supplying connective tissue to enable organ-specific cells to reestablish organ integrity as well as to inhibit excessive scar formation.

Cell paste comprising keratinocytes and fibroblasts

The invention provides a method for delivering biologically active molecules to the eye by implanting biocompatible capsules containing a cellular source of the biologically active molecule. Also provided is a method of treating ophthalmic diseases using biocompatible capsules.

Device and method for treating ophthalmic diseases

This invention provides cells containing recombinant polynucleotides coding for cell surface molecules that, when expressed in the cell, result in rejection of the cell by the host immune system. The invention also provides methods of using such cells, and capsules for delivery of biologically active molecules to a patient.

The invention provides methods of transplanting multipotent neural stem cell progeny to a host by obtaining a population of cells derived from mammalian neural tissue containing at least one multipotent CNS multipotent neural stem cell; culturing the neural stem cell in a culture medium containing one or more growth factors which induce multipotent neural stem cell proliferation; inducing proliferation of the multipotent neural stem cell to produce neural stem cell progeny which includes multipotent neural stem cell progeny cells; and transplanting the multipotent neural stem cell progeny to the host. Also provided are methods of transplanting neural stem cell progeny to a host by obtaining an in vitro cell culture containing CNS neural stem cells where one or more cells in the culture (i) proliferates in a culture medium supplemented with one or more mitrogens, (ii) retains the capacity for renewed proliferation, and (iii) maintains the multipotential capacity, under suitable culture conditions, to differentiate into neurons, astrocytes, and oligodendrocytes; and transplanting the one or more cells to the hose.

Neural transplantation using proliferated multipotent neural stem cells and their progeny

A culture method for determining the effect of a biological agent on multipotent neural stem cell progeny is provided. In the presence of growth factors, multipotent neural stem cells are induced to proliferate in culture. The multipotent neural stem cells may be obtained from normal neural tissue or from a donor afflicted with a disease such as Alzheimer's Disease, Parkinson's Disease or Down's Syndrome. At various stages in the differentiation process of the multipotent neural stem cell progeny, the effects of a biological agent, such as a virus, protein, peptide, amino acid, lipid, carbohydrate, nucleic acid or a drug or pro-drug on cell activity are determined. Additionally, a method of screening the effects of biological agents on a clonal population of neural cells is provided. The technology provides an efficient method for the generation of large numbers of pre- and post-natal neural cells under controlled, defined conditions. The disclosed cultures provide an optimal source of normal and diseased neural cells at various developmental stages, which can be screened for potential side effects in addition to testing the action and efficacy of different biological agents.

Use of multipotent neural stem cells and their progeny for the screening of drugs and other biological agents

Methods for administering genetic material to dividing neural precursor cell populations in vivo are provided. The genetic material may comprise useful genes for neurotransmitters, growth factors, growth factor receptors, and the like. The genetic material is administered to the brain with one or more growth factors. The growth factors induce proliferation of neural precursor cells, thereby facilitating the incorporation of the genetic material into the cell progeny.

In vivo genetic modification of growth factor-responsive neural

The present invention provides novel devices and methods for continuous, controlled delivery of a biologically active molecule to the eye, either intraocularly or periocularly, to treat ophthalmic disorders. A capsule is surgically placed in the desired location in the eye. The capsule includes cells which produce the biologically active molecule. The capsule also includes a surrounding biocompatible jacket through which the biologically active molecule may diffuse into the eye. This jacket may immunoisolate the encapsulated cells, protecting them from attack by the immune system of the patient.

Method for treating ophthalmic diseases

A method for the in vitro proliferation and differentiation of neural stem cells and stem cell progeny comprising the steps of (a) isolating the cells from a mammal, (b) exposing the cells to a culture medium containing a growth factor, (c) inducing the cells to proliferate, and (d) inducing the cells to differentiate is provided.

In vitro growth and proliferation of multipotent neural stem cells and

A method for producing genetically modified neural cells comprises culturing cells derived from embryonic, juvenile, or adult mammalian neural tissue with one or more growth factors that induce multipotent neural stem cells to proliferate and produce multipotent neural stem cell progeny which include more daughter multipotent neural stem cells and undifferentiated progeny that are capable of differentiating into neurons, astrocytes, and oligodendrocytes. The proliferating neural cells can be transfected with exogenous DNA to produce genetically modified neural stem cell progeny. The genetic modification can be for the production of biologically useful proteins such as growth factor products, growth factor receptors, neurotransmitters, neurotransmitter receptors, neuropeptides and neurotransmitter synthesizing genes. The multipotent neural stem cell progeny can be continuously passaged and proliferation reinitiated in the presence of growth factors to result in an unlimited supply of neural cells for transplantation and other purposes. Culture conditions can be provided that induce the genetically modified multipotent neural stem cell progeny to differentiate into neurons, astrocytes, and oligodendrocytes in vitro.

Growing community of inventors

Barrington, RI, United States of America

E Edward Baetge