The present invention provides compositions and methods for the mitigation of side effects of chemotherapy, for example in human subjects with hematologic malignancies (such as lymphoma, leukemia and myelodysplastic syndrome) as well as subjects with other malignancies or other conditions that may be treated with chemotherapy, such as high dose therapy (HOT) or a combination of high dose HDT and a hematopoietic stem cell transplant. The methods comprise administration of endothelial cells, such as engineered human umbilical vein endothelial cells engineered to express the adenoviral E40RF1 protein (E40RF1+HUVECs), to human subjects. The side effects mitigated by the compositions and methods of the invention include, but are not limited to, oral/gastrointestinal side effects and febrile neutropenia.

The present invention provides compositions and methods for the mitigation of side effects of chemotherapy, for example in human subjects with hematologic malignancies (such as lymphoma, leukemia and myelodysplastic syndrome) as well as subjects with other malignancies or other conditions that may be treated with chemotherapy, such as high dose therapy (HOT) or a combination of high dose HDT and a hematopoietic stem cell transplant. The methods comprise administration of endothelial cells, such as engineered human umbilical vein endothelial cells engineered to express the adenoviral E40RF1 protein (E40RF1+HUVECs), to human subjects. The side effects mitigated by the compositions and methods of the invention include, but are not limited to, oral/gastrointestinal side effects and febrile neutropenia.

The present invention relates, in part, to cell-based gene therapies, including those targeting, by way of non-limiting example, TDP43 and Aβ aggregates, for the use in neurodegenerative disorders, including without limitation Amyotrophic Lateral Sclerosis (ALS) and Alzheimer's Disease, respectively.

The present invention relates, in part, to cell-based gene therapies, including those targeting, by way of non-limiting example, TDP43 and Aβ aggregates, for the use in neurodegenerative disorders, including without limitation Amyotrophic Lateral Sclerosis (ALS) and Alzheimer's Disease, respectively.

The devices, methods, and compositions disclosed herein accomplish robust cell encapsulation in polymer microparticles using a vertically oriented microfluidic device. A hydrophilic polymer precursor solution is flowed into a first inlet channel, which extends inward from an upper surface of the device housing. A hydrophobic fluid is flowed into a second inlet channel, which extends inward from a lower surface of the device housing. The two inlet channels meet at a junction, and an outlet channel extends away from the two inlet channels. When the two inwardly flowing streams meet at the junction, the polymer precursor solution disperses into the hydrophobic fluid. The dispersed precursor droplets are photopolymerized into microparticles as they travel through the outlet channel. The resulting microparticles are highly uniform, and are larger than conventionally formed microparticles. Cells of varying types can be encapsulated with high viability and spatial uniformity.

The devices, methods, and compositions disclosed herein accomplish robust cell encapsulation in polymer microparticles using a vertically oriented microfluidic device. A hydrophilic polymer precursor solution is flowed into a first inlet channel, which extends inward from an upper surface of the device housing. A hydrophobic fluid is flowed into a second inlet channel, which extends inward from a lower surface of the device housing. The two inlet channels meet at a junction, and an outlet channel extends away from the two inlet channels. When the two inwardly flowing streams meet at the junction, the polymer precursor solution disperses into the hydrophobic fluid. The dispersed precursor droplets are photopolymerized into microparticles as they travel through the outlet channel. The resulting microparticles are highly uniform, and are larger than conventionally formed microparticles. Cells of varying types can be encapsulated with high viability and spatial uniformity.

It is a subject to provide a means of preparing highly pure vascular endothelial progenitor cells in a simple and low-cost manner. It is also a subject to provide a method for efficiently proliferating vascular endothelial progenitor cells. High-purity vascular endothelial progenitor cells are prepared by the process of differentiating pluripotent stem cells into vascular endothelial progenitor cells and purifying the vascular endothelial progenitor cells using a difference in adhesion ability between the vascular endothelial progenitor cells constituting the cell population obtained in the process and other cells. On the other hand, vascular endothelial progenitor cells are cultured and expanded in the presence of a ROCK inhibitor, a GSK-3β inhibitor, and a TGF-β receptor inhibitor in addition to basic fibroblast growth factor and epidermal growth factor.

It is a subject to provide a means of preparing highly pure vascular endothelial progenitor cells in a simple and low-cost manner. It is also a subject to provide a method for efficiently proliferating vascular endothelial progenitor cells. High-purity vascular endothelial progenitor cells are prepared by the process of differentiating pluripotent stem cells into vascular endothelial progenitor cells and purifying the vascular endothelial progenitor cells using a difference in adhesion ability between the vascular endothelial progenitor cells constituting the cell population obtained in the process and other cells. On the other hand, vascular endothelial progenitor cells are cultured and expanded in the presence of a ROCK inhibitor, a GSK-3β inhibitor, and a TGF-β receptor inhibitor in addition to basic fibroblast growth factor and epidermal growth factor.

The present invention provides a method for producing retinal cells or a retinal tissue, comprising the following steps (1)-(3): (1) a first step of culturing human pluripotent stem cells in the absence of feeder cells and in a medium comprising a factor for maintaining undifferentiated state, (2) a second step of culturing the pluripotent stem cells obtained in the first step in suspension in the presence of a Sonic hedgehog signal transduction pathway activating substance to form a cell aggregate, and (3) a third step of culturing the aggregate obtained in the second step in suspension in the presence of a 1) a BMP signal transduction pathway activating substance to obtain an aggregate containing retinal cells or a retinal tissue.

The present invention provides a method for producing retinal cells or a retinal tissue, comprising the following steps (1)-(3): (1) a first step of culturing human pluripotent stem cells in the absence of feeder cells and in a medium comprising a factor for maintaining undifferentiated state, (2) a second step of culturing the pluripotent stem cells obtained in the first step in suspension in the presence of a Sonic hedgehog signal transduction pathway activating substance to form a cell aggregate, and (3) a third step of culturing the aggregate obtained in the second step in suspension in the presence of a 1) a BMP signal transduction pathway activating substance to obtain an aggregate containing retinal cells or a retinal tissue.