The present disclosure provides means of regenerating/restoring aged and/or damaged tissue or treating a medical condition by providing an extracorporeal circuit containing cells, including fibroblasts or dedifferentiated fibroblasts. that are in contact with plasma but not blood cells extracorporeally in a manner allowing for exchange of factors between a subject and an extracorporeally residing mass of cells. The disclosure provides means of titrating factors produced by the extracorporeal regenerative cell mass, thus allowing for a regenerative effect.

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.

Provided is an isolated population of human pluripotent stem cells comprising at least 50% human pluripotent stem cells characterized by an OCT4+/TRA1-60−/TRA1-81−/SSEA1+/SSEA4− expression signature, and novel methods of generating and maintaining same in a pluripotent, undifferentiated state a suspension culture devoid of cell clumps. Also provided are novel culture media, cell cultures and methods for culturing pluripotent stem cells in a suspension culture or a two-dimensional culture system while maintaining the cells in a proliferative, pluripotent and undifferentiated state. The novel culture media comprise interleukin 11 (IL11) and Ciliary Neurotrophic Factor (CNTF); bFGF at a concentration of at least 50 ng/ml and an IL6RIL6 chimera; or an animal contaminant-free serum replacement and an IL6RIL6 chimera. Also provided are methods for generating lineage-specific cells from the pluripotent stem cells.

Described herein are methods, compositions, and kits for directed differentiation of human pluripotent stem cells into caudal lateral epiblasts, posterior neuroectoderm or posterior neuroepithelium, or motor neurons having specified HOX gene expression pattern mirroring a desired position along the rostral-caudal axis during hindbrain and spinal cord development. Also described are isolated populations of cells including caudal lateral epiblasts, posterior neuroectoderm, posterior neuroepithelium, or motor neurons having a HOX gene expression pattern specified to correspond to the HOX gene expression pattern associated with a desired rostral-caudal axis position.

The present invention relates to a cell culture medium for preparing liver, gastric, pancreatic, colon or intestinal adult stem cell isolated from adult tissue, as well as for maintaining such stem cell in the undifferentiated state. The cell culture medium comprises a base medium; an ABL and SRC dual kinase inhibitor/an ABL kinase inhibitor and a SRC kinase inhibitor; a mitogenic factor; a WNT signalling pathway activator; a stimulator for NAD+ and NADP+ generation; and a cAMP/P KA pathway activator. In a particular embodiment, the ABL and SRC dual kinase inhibitor is Dasatinib; the mitogenic factor is EGF; the WNT signalling pathway activator is R-Spondin 1; the stimulator for NAD+ and NADP+ generation is nicotinamide; and the cAMP/PKA pathway activator is cholera endotoxin.

Use of Cistanche deserticola polysaccharide (CDP) in promoting the proliferation and differentiation of female germline stem cells (FGSCs) is provided. Specifically, the addition of CDP in an in vitro cultivation system can promote the proliferation and differentiation of FGSCs, and especially can enhance the in vitro directed differentiation of FGSCs into oocytes, which provides a new research reference for studying the generation of oocytes in vivo and in vitro and also brings a new hope for research on physiological infertility.

Methods for obtaining populations of norepinephrine (NE) neuronal progenitor cells and creating enriched populations of NE neurons are provided herein. Also provided herein are methods for obtaining genetically modified NE neurons expressing a NE sensor or a TH-reporter, and methods for using NE neurons obtained according to the methods of this disclosure.

The present invention relates to iPSC produced from fibroblast obtained from a subject affected by a neurodevelopmental disorder entailing intellectual disability (ID) and/or a disorder belonging to the Autism Spectrum Disorder (ASD) and/or Schizophrenia (SZ) and uses thereof. The present invention also relates to a cortical neural progenitor cell or a terminally differentiated cortical glutamatergic or gabaergic neuronal cell or a neural crest stem cell line, a mesenchymal stem cell line produced from the iPSC or iPSC line. The invention also relates to method for identifying a compound for the treatment and/or prevention of a neurodevelopmental disorder entailing intellectual disability (ID) and/or a disorder belonging to the Autism Spectrum Disorder (ASD) and/or Schizophrenia (SZ) and to a LSD1 inhibitor or a HDAC2 inhibitor for use in the treatment of such disorders.

The present invention relates to the treatment of sensory neuropathy induced by a marine neurotoxic poisoning. The invention further encompasses an in vitro method for producing a neuro-cutaneous model allowing to study the cellular and/or molecular mechanisms involved in said neuropathy, a neuro-cutaneous model obtainable according to said method, and applications thereof.

The invention relates to a method for producing cartilage from pluripotent stem cells (PSCs), the method comprising providing chondrocytes by: 1) providing pluripotent stem cells (PSCs); 2) inducing differentiation of the PSCs into a primitive streak/mesendoderm by culturing the PSCs in hypoxic conditions, in a (mesendodermic) culture media comprising: i) a Wingless/Integrated (WNT) family member, ii) an Activin family member, and iii) a Fibroblast Growth Factor (FGF) family member; 3) inducing differentiation of the primitive streak/mesendoderm into a mesoderm by culturing the primitive streak/mesendoderm in hypoxic conditions, in a (mesodermic) culture media comprising: i) a FGF family member, ii) a bone morphogenetic protein (BMP) family member, iii) Follistatin, and iv) a Neurotrophin (NT); and 4) inducing differentiation of the mesoderm into chondrocytes by culturing the mesoderm in hypoxic conditions, in a (chondroinductive) culture media comprising: i) a FGF family member, ii) a BMP family member, iii) a Neurotrophin, and iv) a Growth/Differentiation Factor (GDF) family member; and forming a pellet of the chondrocytes and culturing the pellet of the chondrocytes in a culture media under hypoxic conditions to produce the cartilage. The invention further relates to methods of chondrocyte production, synthetically produced cartilage, and use in therapy.