The present disclosure provides a method of manufacturing and differentiating mammalian stem cells, and in one embodiment human induced pluripotent stem cells (iPSc), e.g., manufacturing neuron progenitors, e.g., derived from iPSC, on a large scale by the use of an automated hollow fiber reactor system. In one embodiment, human iPSc that can be differentiated into cardiomyocytes or neuron progenitors are provided. The method comprises seeding a hollow fiber reactor with stem cells such as iPSc, or differentiated iPSc, growing and expanding the seeded cells using appropriate growth factors and nutrients, and harvesting the cells after expansion from the hollow fiber reactor walls, e.g., with the use of an enzyme. The method can produce billions of cells per week from seeding the reactor with a minimum number of starting stem cells or neuron progenitor cells.

An object of the present invention is to provide a method for removing highly proliferative Ki67-positive cells co-present in insulin-secreting cells obtained by differentiation induction. A method for producing an insulin-producing cell population or a pancreatic beta cell population containing less than 3% of Ki67-positive cells, comprising: embedding an endocrine progenitor cell population or a cell population at a later stage of differentiation into a gel containing alginic acid; and differentiating the cell population.

A method for predicting an effect of a medication or a treatment regimen to a subject suffering from a cancer, the method comprises: (A) obtaining a tissue from the subject; (B) dissociating the tissue to obtain a multicellular cluster, wherein the multicellular cluster comprises the cancer cell; (C) culturing the multicellular cluster on a cellulose sponge; (D) exposing the cultured multicellular cluster to the medication or the treatment regimen; and (E) measuring a first survival rate of the cancer cell before exposing to the medication or the treatment regimen and a second survival rate of the cancer cell after exposing to the medication or the treatment regimen, when the second survival rate is lower than the first survival rate, the method predicts positive effect of the medication or the treatment regimen to the subject.

The present application provides non-naturally occurring 3D brown adipose-derived stem cell (BADSC) aggregates, methods of making the 3D BADSC aggregates, and methods of using the 3D BADSC aggregates.

The present disclosure relates to method for drying hydrogel comprising nanofibrillar cellulose, the method comprising providing a hydrogel comprising nanofibrillar cellulose, providing polyethylene glycol, providing trehalose, mixing the hydrogel, the polyethylene glycol and the trehalose to obtain a mixture, and freeze drying the mixture to obtain a dried hydrogel comprising nanofibrillar cellulose. The present disclosure relates to a freeze-dryable hydrogel comprising nanofibrillar cellulose, to a freeze-dried hydrogel comprising nanofibrillar cellulose, and to a medical hydrogel comprising nanofibrillar cellulose and one or more therapeutic agent(s).

A nanofibrillar cellulose hydrogel is disclosed. The nanofibrillar cellulose hydrogel may comprise azido-modified nanofibrillar cellulose having a substituent represented by the formula O(CH.sub.2).sub.nS(O).sub.m-L.sub.1-N.sub.3, wherein n is in the range of 1 to 10; m is 0 or 1; and L.sub.1 is a linker; wherein the substituent is attached to a carbon of one or more glucosyl units of the azido-modified nanofibrillar cellulose, thus forming an ether bond to the carbon.

The present disclosure relates to cultured adipose tissue. In one embodiment, the cultured adipose tissue is produced by culturing adipose cells in a culture media in vitro, harvesting the adipose cells after a desired amount of adipose cells are produced, and aggregating the harvested adipose cells to provide the cultured adipose tissue. In some embodiments, aggregating the harvested adipose cells comprises mixing the harvested adipose cells with a hydrogel or binder in a three-dimensional (3D) mold. In other embodiments, aggregating the harvested adipose cells comprises cross-linking the harvested adipose cells in a 3D mold. The cultured adipose tissue have a defined 3D shape and a size on the macroscale. In some embodiments, the cultured adipose tissue may be a food product.

The present invention relates to preparation and use of biocompatible and electrically conductive 3D hydrogels comprising nanocellulose fibrils, such as disintegrated bacterial nanocellulose, plant derived nanocellulose, tunicate derived nanocellulose, or algae derived nanocellulose, together with carbon nanotubes or graphene oxide, as a biocompatible and conductive 3D hydrogel for diagnostics and intervention to mimic or restore tissue and organ function. Biocompatible conductive 3D hydrogels described in this invention can be extruded, casted or injected. The 3D hydrogels described in this invention are cohesive 3D structures and provide electrical conductivity in wet form. 3D hydrogels described in this invention can be further crosslinked using divalent ions such as Calcium ions which improve mechanical stability. Such crosslinking can take place in an animal or human body in a physiological environment after injection into the tissue. 3D hydrogels are biocompatible and show preferable mechanical properties and electrical conductivity through printed lines (4.10.sup.1 S cm.sup.1). The 3D hydrogels prepared by this invention are suited as bioassays to screen drugs against neurodegenerative diseases such as Alzheimer's and Parkinson's, study brain function, and/or be used to link the human brain with electronic and/or communication devices. They can also be injected to replace neural tissue or stimulate guiding of neural cells. They can also be used to inject into the heart and stimulate the heart by using electrical signaling or to repair myocardial infarction.

A collagen-fibronectin-based method enables the production of tumors of centimeter size with recognizable pathological traits. The method supports reproducing tumor heterogeneity with preinvasive and invasive phenotypes and stacking of tumor portions using a paper-scaffold with 80 m-punched holes for larger nodule creation and easy separation of tumor portions for analysis. Macrotumors are convenient for testing drug delivery and therapeutic tools that necessitate a minimum tumor size relevant to in vivo.

A new type of kidney miniature organoids based on human embryonic stem cells are prepared and tested as forming cysts in vitro or ex vivo. Assays are developed for screening useful candidate molecules towards inhibiting or treating polycystic kidney disease. This provides a new system for modeling polycystic kidney disease.