Patent classifications
A61K35/44
COMPOSITIONS AND METHODS FOR THYMIC REGENERATION AND T-CELL RECONSTITUTION
The present invention provides non-thymic endothelial cells (ntECs) engineered to express adenovirus E4ORF1 and/or BMP4, and compositions comprising such engineered ntECs. The present invention also provides methods of using such ntECs in therapy, for example to enhance thymic regeneration (including T cell reconstitution) in subjects in need thereof. Such subjects include those that have a damaged thymus, defective thymic function, insufficient T-cell output, and/or that are immunocompromised—for example as a result of ageing, infection (e.g. with HIV), treatment with radiation therapy, treatment with chemotherapy, or myeloablative conditioning in preparation for an organ/tissue transplant.
COMPOSITIONS AND METHODS FOR THYMIC REGENERATION AND T-CELL RECONSTITUTION
The present invention provides non-thymic endothelial cells (ntECs) engineered to express adenovirus E4ORF1 and/or BMP4, and compositions comprising such engineered ntECs. The present invention also provides methods of using such ntECs in therapy, for example to enhance thymic regeneration (including T cell reconstitution) in subjects in need thereof. Such subjects include those that have a damaged thymus, defective thymic function, insufficient T-cell output, and/or that are immunocompromised—for example as a result of ageing, infection (e.g. with HIV), treatment with radiation therapy, treatment with chemotherapy, or myeloablative conditioning in preparation for an organ/tissue transplant.
A METHOD FOR INCREASING POPULATION OF SPERMATOGONIAL STEM CELLS
Maintenance of adult tissues depends on stem cell self-renewal in local niches. Spermatogonial stem cells (SSC) are germline adult stem cells necessary for spermatogenesis and fertility. The present invention relates utilization of testicular endothelial cells (TECs) in the SSC niche producing glial cell line-derived neurotrophic factor (GDNF) and other factors to support human and mammal SSCs in long-term culture. The present invention also relates to utilization of five factors sufficient for long-term maintenance of human and mammal SSC colonies in feeder-free cultures. Male cancer survivors after chemotherapy are often infertile since SSCs are highly susceptible to cytotoxic injury. Transplantation of TECs alone is used to restore spermatogenesis in mice after chemotherapy-induced depletion of SSCs.
A METHOD FOR INCREASING POPULATION OF SPERMATOGONIAL STEM CELLS
Maintenance of adult tissues depends on stem cell self-renewal in local niches. Spermatogonial stem cells (SSC) are germline adult stem cells necessary for spermatogenesis and fertility. The present invention relates utilization of testicular endothelial cells (TECs) in the SSC niche producing glial cell line-derived neurotrophic factor (GDNF) and other factors to support human and mammal SSCs in long-term culture. The present invention also relates to utilization of five factors sufficient for long-term maintenance of human and mammal SSC colonies in feeder-free cultures. Male cancer survivors after chemotherapy are often infertile since SSCs are highly susceptible to cytotoxic injury. Transplantation of TECs alone is used to restore spermatogenesis in mice after chemotherapy-induced depletion of SSCs.
GENERATING VASCULOGENIC CELL POPULATIONS
The present invention relates generally to methods and compositions useful for therapeutic vascular tissue engineering. In particular, the present invention provides methods for generating substantially pure populations of vasculogenic cells from human mesenchymal progenitors, and methods and compositions for clinical applications in the field of regenerative medicine.
GENERATING VASCULOGENIC CELL POPULATIONS
The present invention relates generally to methods and compositions useful for therapeutic vascular tissue engineering. In particular, the present invention provides methods for generating substantially pure populations of vasculogenic cells from human mesenchymal progenitors, and methods and compositions for clinical applications in the field of regenerative medicine.
ENGINEERED ENDOTHELIAL CELLS EXPRESSING AN ETS TRANSCRIPTION FACTOR
In some aspects the present invention relates to engineered endothelial cells, such as E4ORF1+ ETV2+ engineered endothelial cells. In other aspects the present invention relates to methods of making such engineered endothelial cells, and methods of using such engineered endothelial cells, for example in co-culture applications.
ENGINEERED ENDOTHELIAL CELLS EXPRESSING AN ETS TRANSCRIPTION FACTOR
In some aspects the present invention relates to engineered endothelial cells, such as E4ORF1+ ETV2+ engineered endothelial cells. In other aspects the present invention relates to methods of making such engineered endothelial cells, and methods of using such engineered endothelial cells, for example in co-culture applications.
THERAPEUTIC HYDROGEL DEVICE
The present invention generally relates to a therapeutic hydrogel device. More particularly, the present invention describes various embodiments of a hydrogel macrodevice, such as a planar hybrid hydrogel macrodevice that can achieve spatially controlled distribution of microtissues and support establishment of intra-device vasculature for enhanced cell survival, and individually encapsulated microtissues, and methods of use.
THERAPEUTIC HYDROGEL DEVICE
The present invention generally relates to a therapeutic hydrogel device. More particularly, the present invention describes various embodiments of a hydrogel macrodevice, such as a planar hybrid hydrogel macrodevice that can achieve spatially controlled distribution of microtissues and support establishment of intra-device vasculature for enhanced cell survival, and individually encapsulated microtissues, and methods of use.