Abstract: Pluripotent stem cell-derived 3D retinal organoid compositions and methods of making using the same are disclosed.

Abstract: Aspects of the present invention include methods and compositions related to the production and use of numerous clonal lineages of embryonic progenitor cell lines derived from differentiating cultures of primordial stem cells with diverse molecular markers and having been cultured for >21 doublings of clonal expansion. The robustness of these clonally-purified lines, their ability to expand for >40 passages while maintaining their pattern of gene expression, lack of tumorigenicity, and their embryonic pattern of gene expression offers novel compositions and methods for modeling numerous differentiation pathways for the first time in vitro, and for the manufacture of purified product not existing in such a purified state in nature or using other manufacturing modalities. Representative progenitor cell lines described herein are capable of development into cutaneous adipocytes, blood-brain barrier cells, neuronal cells, or smooth muscle cells each with therapeutic potential.

Abstract: Aspects of the present invention include methods and compositions related to the production and use of clonal lineages of embryonic progenitor cell lines derived from differentiating cultures of primordial stem cells, in particular, said methods and compositions relate to methods of differentiating cells in the presence of members of the BMP family of growth factors and the applications of said cell lines in the treatment of degenerative orthopedic diseases such as osteoarthritis.

Abstract: Described herein are compositions and methods for treating retinal diseases or disorders using RPE cells.

Abstract: Methods for differentiating pluripotent stem cells to neuroectoderm in dynamic suspension culture using small molecule or protein inhibitors of TGF?/Activin/Nodal signaling and BMP signaling are provided. Also provided are methods and protocols for differentiating pluripotent stem cells such as human embryonic stem cells first to neuroectoderm, then further to glial progenitor cells, and further to oligodendrocyte progenitor cells (OPCs), and compositions obtained thereby. The methods of the present disclosure reproducibly produce neuroectoderm progenitor cells by day 7 of the differentiation process, glial progenitor cells by day 21 of the differentiation process and OPCs by day 42 of the differentiation process.

Abstract: Disclosed are biologically active protein conjugates that comprise a biologically active polypeptide coupled via a peptide bond to a polypeptide comprising from 2 to about 500 units of a repeating peptide motif, wherein the biologically active protein conjugate exhibits a modified plasma half-life compared to the intrinsic half-life of the unconjugated biologically active polypeptide or protein. Also disclosed are methods of making and using the conjugated proteins, as well as methods for determining whether a given conjugate exhibits a modified half life relative to the intrinsic half life of the unconjugated polypeptide.

Abstract: The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to oxygen linked and substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative disorders including tumours and cancers as well as other disorders or conditions related to or associated with kinases.

Abstract: A compound of general formula (I): in which: R is selected from the group consisting of (C1-C25)alkyl, (C2-C25)alkenyl, aryl, (C7-C10)aralkyl; n and m are each independently an integer of two to eight; p is one or two; A is selected from the group consisting of —B—, —B—(CH2)r—B—, —B—(CH2)r—B—(CH2)z—B—, wherein r and z are an integer from 2 to 8, B is a —NR1— or —N(R2)2+1/pQ?p group, in which R1 is selected from hydrogen, (C1-C4)alkyl, (C1-C4)acyl, tert-butoxycarbonyl, and R2 is selected from hydrogen and (C1-C4)alkyl; Q?p is an anion selected from chloride, bromide, iodide, nitrate, sulphate, hydrogen sulphate, perchlorate, R3COO? wherein R3 has the same meanings as R, independently from one another and R4—O—SO3? wherein R4 is (C2-C14)alkyl with the proviso that, when Q?p is selected from chloride, bromide, iodide, nitrate, sulphate, hydrogen sulphate, perchlorate, R is not (C1-C4)alkyl.

Abstract: The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to oxygen linked and substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative disorders including tumors and cancers as well as other disorders or conditions related to or associated with kinases.

Abstract: The present invention provides a method of increasing neural stem cell numbers or neurogenesis by using prolactin. The method can be practiced in vivo to obtain more neural stem cells in situ, which can in turn produce more neurons or glial cells to compensate for lost or dysfunctional neural cells. The method can also be practiced in vitro to produce a large number of neural stem cells in culture. The cultured stem cells can be used, for example, for transplantation treatment of patients or animals suffering from neurodegenerative diseases or conditions. In addition, since neural stem cells are a source for olfactory neurons, the present invention also provides methods of increasing olfactory neurons and enhancing olfactory functions.

Abstract: The invention relates to an improved process for the preparation of poly-?-glutamic acids which comprises the polymerization of tertiary ?-esters of ?-glutamic acid N-carboxy anhydride with appropriate solvents and initiators, followed by acid hydrolysis of the resulting poly-?-glutamic acid-?-ester. The process is particularly advantageous in that it allows one to carefully control the molecular weight of the resulting poly-?-glutamic acid. The invention also relates to poly-?-glutamic acids capped at the amino terminus with carboxylic acids or amino acids and to a process for the preparation thereof.

Abstract: The invention relates to a method for determining the amount of conjugated taxane, in particular paclitaxel, in a PGA-taxane conjugate said method comprising: a) reacting the PGA-taxane conjugate with a compound formula (I): R1R2N—NH2 (I), wherein R1 and R2 are as defined in the description; to give a unbound taxane and a PGA hydrazide and b) determining the amount of unbound taxane.

Abstract: Disclosed are biologically active protein conjugates that comprise a biologically active polypeptide coupled via a peptide bond to a polypeptide comprising from 2 to about 500 units of a repeating peptide motif, wherein the biologically active protein conjugate exhibits a modified plasma half-life compared to the intrinsic half-life of the unconjugated biologically active polypeptide or protein. Also disclosed are methods of making and using the conjugated proteins, as well as methods for determining whether a given conjugate exhibits a modified half life relative to the intrinsic half life of the unconjugated polypeptide.

Abstract: This invention relates to methods of producing oligodendrocytes from multipotent neural stem cells by using at least one oligodendrocyte promoting factor, particularly granulocyte-macrophage colony stimulating factor, granulocyte colony stimulating factor, interleukin 3 or interleukin 5. The neural stem cells may optionally be expanded prior to being subjected to the oligodendrocyte promoting factor.

Abstract: The present invention provides a method of increasing neural stem cell numbers or neurogenesis by using prolactin. The method can be practiced in vivo to obtain more neural stem cells in situ, which can in turn produce more neurons or glial cells to compensate for lost or dysfunctional neural cells. The method can also be practiced in vitro to produce a large number of neural stem cells in culture. The cultured stem cells can be used, for example, for transplantation treatment of patients or animals suffering from neurodegenerative diseases or conditions. In addition, since neural stem cells are a source for olfactory neurons, the present invention also provides methods of increasing olfactory neurons and enhancing olfactory functions.

Abstract: Disclosed are biologically active protein conjugates that comprise a biologically active polypeptide coupled via a peptide bond to a polypeptide comprising from 2 to about 500 units of a repeating peptide motif, wherein the biologically active protein conjugate exhibits a modified plasma half-life compared to the intrinsic half-life of the unconjugated biologically active polypeptide or protein. Also disclosed are methods of making and using the conjugated proteins, as well as methods for determining whether a given conjugate exhibits a modified half life relative to the intrinsic half life of the unconjugated polypeptide.

Abstract: An isolated human cell is disclosed comprising at least one mesenchymal stem cell phenotype and secreting brain-derived neurotrophic factor (BDNF), wherein a basal secretion of the BDNF is at least five times greater than a basal secretion of the BDNF in a mesenchymal stem cell. Methods of generating same and uses of same are also disclosed.

Abstract: The present invention provides a method of increasing neural stem cell numbers or neurogenesis by using prolactin. The method can be practiced in vivo to obtain more neural stem cells in situ, which can in turn produce more neurons or glial cells to compensate for lost or dysfunctional neural cells. The method can also be practiced in vitro to produce a large number of neural stem cells in culture. The cultured stem cells can be used, for example, for transplantation treatment of patients or animals suffering from neurodegenerative diseases or conditions. In addition, since neural stem cells are a source for olfactory neurons, the present invention also provides methods of increasing olfactory neurons and enhancing olfactory functions.

Abstract: The invention relates to an improved process for the preparation of poly-?-glutamic acids which comprises the polymerization of tertiary ?-esters of ?-glutamic acid N-carboxy anhydride with appropriate solvents and initiators, followed by acid hydrolysis of the resulting poly-?-glutamic acid-?-ester. The process is particularly advantageous in that it allows one to carefully control the molecular weight of the resulting poly-?-glutamic acid. The invention also relates to poly-?-glutamic acids capped at the amino terminus with carboxylic acids or amino acids and to a process for the preparation thereof.

Abstract: The present invention is related to the discovery of a novel class of neural progenitor cells, which proliferate in response to platelet derived growth factor (PDGF) and differentiate into neurons and oligodendrocytes but not astrocytes. Progeny of the progenitor cells can be obtained by culturing brain tissue in PDGF without serum, epidermal growth factor (EGF), fibroblast growth factor 2, or transforming growth factor alpha. Upon subculturing into EGF-containing media, these progeny cells can proliferate and form neurospheres, whereas PDGF has no such effect.