A developmental toxicity screening assay using spatially organized cardiac organoids with contracting cardiomyocytes in the center surrounded by stromal cells distributed along the pattern perimeter engineered from human induced pluripotent stem cells (hiPSCs). Cardiac organoids generated from 600 μm-diameter circles were used as a developmental toxicity screening assay for the quantification of the embryotoxic potential of nine pharmaceutical compounds. The cardiac organoids were demonstrated as having a potential use as an in vitro platform for studying organoid structure-function relationships, developmental processes, and drug-induced cardiac developmental toxicity.

Embodiments of the disclosure concern compositions and methods of use related to particular immortalized cells, including cardiac stem cells, obtained from a pediatric or neonatal individual. In specific embodiments, the immortalized cells, or conditioned medium from the cells, or partial or total secretomes thereof, are provided in an effective amount to an individual in need thereof either alone or in combination with cardiac stem cells.

A method for producing a mesenchymal cell line derived from a vertebrate adipose tissue, and a mesenchymal cell line derived from a vertebrate adipose tissue produced by the method. Advantageously, a method for producing a mesenchymal cell line derived from a vertebrate adipose tissue is achieved more simply, in a shorter period of time, and more efficiently. Also, a mesenchymal cell line is derived from a vertebrate adipose tissue produced by the production method. The method for producing a mesenchymal cell line derived from a vertebrate adipose tissue comprises: (A) inducing differentiation of one or more cells selected from a stromal vascular fraction comprising a mesenchymal stem cell, an adipose progenitor cell, and a stromal cell of a vertebrate adipose tissue into a mature adipocyte; and (B) inducing dedifferentiation of the mature adipocyte obtained in step (A) to obtain a mesenchymal cell line derived from the vertebrate adipose tissue.

Complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide are provided. Compositions and methods for delivery of complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide to mammals for both research and therapeutic use are provided. Methods of treating or reducing one or more symptoms of type 2 diabetes, prediabetes and/or gestational diabetes are provided.

The present invention provides a new method related to regenerative medicine for the treatment of cartilage disorders, osteoarthritis and cartilage injury in particular. More particularly, it relates to an FGF-18 compound for use in tissue engineering and graft procedures, such as osteochondral or cartilage transplantation or autologous chondrocyte implantation (ACI).

Methods and compositions are disclosed for repair of shoulder injuries by employing disaggregated muscle fiber fragments to regenerate functional shoulder muscle tissue. In some embodiments, the fragments retain functional satellite cells but exhibit cell wall rupture and have an average size of less than 150 μm. The methods include the preparation and implantation of compositions by extracting muscle tissue from a donor site, disaggregating muscle fibers from the extracted tissue, and fragmenting disaggregated muscle fibers into fiber fragments that exhibit cell wall rupture and preferably have an average size of less than 150 microns, more preferable less than about 100 microns, while retaining functional satellite cells. Upon injection, e.g., into the supraspinatus or other rotator cuff muscles, the muscle fiber fragment compositions are capable of reconstituting or reconstructing elongated muscle fibers from the fragments and orienting in alignment with native shoulder muscle fibers.

Biocompatible macroporous microcarriers, including microcarrier beads, microspheres, capsules, microsponges, hydrogels and other matrix forms, appropriate for use in a shaking flask or bioreactor to culture cells are described herein that can be used to create an edible structure for consumption or research investigation. Biocompatible, macroporous microcarriers can be dissolved or remain in the final product. Biocompatible macroporous microcarriers are formed by saccharides that are cross-linked via chemical induction with agitated cryo-gelation. Cross-linked macroporous, saccharide-microcarriers are coupled to adherence factors that enable cell binding. Finally, the cells are attached to the microcarrier for proliferation.

There is provided a method of inducing differentiation of bone marrow stromal cells to neural cells or skeletal muscle cells by introduction of a Notch gene. Specifically, the invention provides a method of inducing differentiation of bone marrow stromal cells to neural cells or skeletal muscle cells in vitro, which method comprises introducing a Notch gene and/or a Notch signaling related gene into the cells, wherein the finally obtained differentiated cells are the result of cell division of the bone marrow stromal cells into which the Notch gene and/or Notch signaling related gene have been introduced. The invention also provides a method of inducing further differentiation of the differentiation-induced neural cells to dopaminergic neurons or acetylcholinergic neurons. The invention yet further provides a treatment method for neurodegenerative and skeletal muscle degenerative diseases which employs neural precursor cells, neural cells or skeletal muscle cells produced by the method of the invention.

The present invention provides compounds of formula I: ##STR00001##
or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds, and methods of using such compounds for treatment of joint damage or joint injury in a mammal, and for inducing differentiation of mesenchymal stem cells into chondrocytes.

Disclosed is an apparatus for the production of tissue from cells. The apparatus comprises an elongate body having at least one circumferential groove and being operable to extend, by close-fitting relationship, centrally through at least one trough. The troughs are extending in a closed path, such that the at least one of the circumferential grooves open into an inner edge of a trough. Also disclosed is a process for production of tissue from cells, via a transitioning intermediate which transitions from the cells into the tissue.