The subject matter of the present invention is a method for differentiating epithelial stem cells, comprising culturing one or more epithelial stem cells in contact with an extracellular matrix in the presence of an expansion medium, a bovine pituitary extract, a receptor tyrosine kinase ligand, a supernatant of primary fibroblasts and optionally, a Rho kinase inhibitor.

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

The present invention relates to microfluidic fluidic devices, methods and systems as microfluidic kidney on-chips, e.g. human Proximal Tubule-Kidney-Chip, Glomerulus (Kidney)-Chip, Collecting Duct (Kidney)-Chip. Devices, methods and systems are described for drug testing including drug transport and renal clearance. Further, such devices, methods and systems are used for determining drug-drug interactions and their effect upon renal transporter functions. Importantly, they may be used for pre-clinical and clinical drug development for treating kidney diseases and for personalized medicine.

An object of the present invention is to provide a ventral hindgut organoid for producing a bladder organoid that comprises a layer structure of bladder epithelial cell types like the urinary bladder. An aspect of the present invention is to provide a method for producing a ventral hindgut organoid, comprising culturing a pluripotent stem cell with an inducer medium A containing activin A and GSK3β inhibitor to induce differentiation into definitive endoderm cells and culturing the definitive endoderm cells with an inducer medium B containing fibroblast growth factor, GSK3β inhibitor, and optionally further containing bone morphogenetic protein, and then culturing them in the presence of extracellular matrix with an inducer medium B containing fibroblast growth factor, GSK3β inhibitor, and optionally further containing bone morphogenetic protein to form a ventral hindgut organoid.

In various aspects and embodiments, the present invention provides methods for preparing innervated tissue. In various embodiments the invention further provides innervated tissue generated using the methods described herein. In various embodiments the inclusion of optogenetically transducible TENGs or Micro-TENNs in the innervated tissue allows the modulation of tissue or organs by using light to stimulate the optogenetically transducible TENGs or Micro-TENNs.

The present invention aims to provide a method for preparing urothelial cells that can be applied to the treatments of urologic diseases, particularly, diseases caused by urothelial cell damage, diseases caused by loss of urothelial cells and dysfunction, and the like, urothelial cells prepared by said method, and a medium for inducing (generating) urothelial cells. Urothelial cells prepared by a method for inducing a urothelial cell, including a step of introducing at least one member selected from the group consisting of

FOXA1 (Forkhead box A1) gene or an expression product thereof,
TP63 (tumor protein P63) gene or an expression product thereof,
MYCL (L-Myc) gene or an expression product thereof, and
KLF4 (Kruppel-like factor 4) gene or an expression product thereof
to a mammalian somatic cell as an exogeneous factor can be applied to the treatment of urologic diseases.

The present disclosure is related to a perfusable-type bio-dual proximal tubule cell construct and a producing method thereof capable of applying an in vitro artificial organ model configured to include a first bioink comprising a decellularized substance derived from a mammalian kidney tissue and human umbilical vascular endothelial cells (HUVECs) and a second bioink comprising the decellularized substance and renal proximal tubular epithelial cells (RPTECs), wherein the first bioink and the second bioink are coaxial and printed in tubular constructs having different inner diameters.

According to the present disclosure, it is possible to use the renal proximal tubule-on-a-chip as a bioreactor capable of observing a biological drug reaction similar to a real drug by perfusing various drugs to the renal proximal tubule-on-a-chip.

The invention discloses a methodology for the biomimetic culture of urothelial cells from mammalian bladders, including murine, porcine, bovine and human sources to isolate and expand urothelial cells for use in various applications, such as intravesical urothelial cell therapy to treat cystitis and bladder cancer.

The present invention relates to a 3 dimensional mimetic tissue structureAssembloid based on patient-derived multiple cell types to develop next generation organoid technology serving as a novel platform for new drug development and a disease model and a method of manufacturing the same, and more particularly, to a stem cell- or tumor cell-based 3D multicellular mimetic tissue structure manufactured by reconstituting epithelial or tumor cells with various cellular components of a microenvironment such as stromal cells, vascular cells, immune cells or muscle cells based on three-dimensional (3D) bioprinting, and a method of manufacturing the same. As the stem cell- or tumor cell-based 3D multicellular mimetic tissue structure containing the major factors of a tissue microenvironment, such as stromal cells, vascular cells, immune cells and muscle cells, designed according to the present invention is confirmed to mimic physiological and pathological characteristics of tissue in the body better than conventional organoids, normal and tumor assembloids may be used as a new platform for new drug development and a disease model. More specifically, together with 3D bioprinting technology, it is expected that in vitro bladder tissue and bladder tumor tissue are effectively used as a platform to develop precise and personalized therapeutic options for bladder related diseases including bladder cancer.

The present disclosure is related to a perfusable-type bio-dual proximal tubule cell construct and a producing method thereof capable of applying an in vitro artificial organ model configured to include a first bioink comprising a decellularized substance derived from a mammalian kidney tissue and human umbilical vascular endothelial cells (HUVECs) and a second bioink comprising the decellularized substance and renal proximal tubular epithelial cells (RPTECs), wherein the first bioink and the second bioink are coaxial and printed in tubular constructs having different inner diameters. According to the present disclosure, it is possible to use the renal proximal tubule-on-a-chip as a bioreactor capable of observing a biological drug reaction similar to a real drug by perfusing various drugs to the renal proximal tubule-on-a-chip.