Systems and methods for tissue engineered synthetic support structures, such as grafts and patches are provided. The systems and methods can be used to make tissue engineered planar sheathes or meshes that can be fashioned into substantially planar or non-planar 3D tissue/organ structures adaptable to structure and organs within a human or mammalian body. The systems and methods can use bioink deposited on a material having specified properties and matured under specified conditions to create the tissue engineered planar sheathes or meshes having biomechanical and biological properties tailored to a particular tissue.

Animal cells, notably adult fibroblasts, are advantageously reprogrammed in direct lineage reprogramming methods using defined factors to produce proliferative and multipotent induced cardiac progenitor cells (iCPC). The iCPC thus produced can be differentiated under suitable differentiation conditions to cardiac lineage cells including cardiomyocytes, smooth muscle cells, and endothelial cells, as evidenced by expression of lineage specific markers. Sets of factors effective in combination to reprogram the fibroblasts can include a set that includes some or all of 5 factors (Mesp1, Baf60c, Nkx2.5, Gata4, Tbx5), a set that includes some or all of 11 factors (Mesp1, Mesp2, Gata4, Gata6, Baf60c, SRF, Isl1, Nkx2.5, Irx4, Tbx5, Tbx20), a set that includes some or all of 18 factors (T, Mesp1, Mesp2, Tbx5, Tbx20, Isl1, Gata4, Gata6, Irx4, Nkx2.5, Hand1, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2), and a set that includes some or all of 22 factors (T, Mesp1, Mesp2, Tbx5, Tbx20, Isl1, Gata4, Gata6, Irx4, Nkx2.5, Hand1, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2, Oct4, Klf4, Sox2, L-myc).

This invention relates, e.g., to a Myocyte-based Flow Assist Device (MFAD) for treating a subject in need of increased flow of a biological fluid, such as venous blood or lymph, comprising a sheath which comprises rhythmically contracting myocytes.

This disclosure relates to methods of making vascular smooth muscle like cells from precursor stem cells. In certain embodiments the vascular smooth muscle like cells are able to contract in response to vasoactive agents, In certain embodiments, the methods comprise contacting pluripotent stem cells with a mesoderm induction growth medium, followed by replicating the cells in a serum-free vascular smooth muscle cell growth medium in the presence of collagen, and purifying replicated cells that express cadherin-2. In certain embodiments, the purified cells are used to treat or prevent a cardiovascular disease or condition.

Using BK Channels as non-genomic estrogen targets in order to alleviate overactive bladder.

The present invention relates to inter alia, methods for the generation and maintenance of Mesoderm-derived ISL1+ Multipotent Progenitors (IMPs), the production of a number of pluripotent cells including and epicardial pluripotent cells (EPCs) and using these cells to produce endothelial cells, cardiomyocytes, smooth muscle cells, vascular cells and other cells and related methods as otherwise disclosed herein. The invention also relates to compositions comprising a population of cells.

Means which enables preparation of a thick cell aggregate by a simple process without an operation of detaching and stacking of cells is disclosed. The method for preparing a three-dimensional cell aggregate by the present invention comprises: a cell encasing step of placing a cell suspension in a cell container; and a pressure application step of applying pressure to cells in the container. The cell encasing step and the pressure application step may be carried out a plurality of times. By the present invention, a thick, robust cell aggregate can be obtained by a simple operation of applying pressure to a cell suspension or a medium containing cells.

Since the method does not require an operation of stacking a plurality of cell sheets, the cells are hardly damaged, and the conditions of the cells can be favorably maintained, so that the cells can be advantageously used as a tissue piece for transplantation.

The generation of complex organ tissues from human embryonic and pluripotent stem cells (PSCs) remains a major challenge for translational studies. It is shown that PSCs can be directed to differentiate into intestinal tissue in vitro by modulating the combinatorial activities of several signaling pathways in a step-wise fashion, effectively recapitulating in vivo fetal intestinal development. The resulting intestinal “organoids” were three-dimensional structures consisting of a polarized, columnar epithelium surrounded by mesenchyme that included a smooth muscle-like layer. The epithelium was patterned into crypt-like SOX9-positive proliferative zones and villus-like structures with all of the major functional cell types of the intestine. The culture system is used to demonstrate that expression of NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis is sufficient to promote differentiation towards the enteroendocrine cell lineage. In conclusion, PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development, homeostasis and disease.

The invention provides a quiescent stem cell having the capacity to differentiate into ectoderm, mesoderm and endoderm, and which does not express cell surface markers including MHC class I, MHC class II, CD44, CD45, CD13, CD34, CD49c, CD73, CD105 and CD90. The invention further provides a proliferative stem cell, which expresses genes including Oct-4, Nanog, Sox2, GDF3, P16INK4, BMI, Notch, HDAC4, TERT, Rex-1 and TWIST but does not express cell surface markers including MHC class I, MHC class II, CD44, CD45, CD13, CD34, CD49c, CD73, CD105 and CD90. The cells of the invention can be isolated from adult mammals, have embryonic cell characteristics, and can form embryoid bodies. Methods for obtaining the stem cells, as well as methods of treating diseases and the differentiated stem cells, are also provided.

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.