A serum-free complete medium for inducing differentiation of a mesenchymal stem cell to a corneal epithelial cell in the field of differentiation induction of stem cells, prepared by the following method: uniformly mixing the serum-free complete medium, containing 5-10 ?mol of resveratrol, 2-4 ?mol of icariin, 1-3 nmol of aspirin, 1-3 nmol of parathyroid hormone, 5-10 nmol of hydrocortisone, 1-3 mg of rapamycin, 2-10 ?g of testosterone, 2-10 ?g of EPO, 2-10 ?g of LIF and the balance of a corneal epithelial cell serum-free medium in per 1 L; and then performing sterilization by filtration. The disclosure uses resveratrol and icariin in combination with aspirin, parathyroid hormone, hydrocortisone, rapamycin, testosterone and growth factors to cooperatively induce directional differentiation, uses nontoxic induction components, is high in induction efficiency and short in induction time, and achieves high induced corneal epithelial cell activity, no cell transplantation rejection, no ethical problem and high safety.

Embodiments of chemically defined cell culture media containing nutrients and growth factors free of any serum for culturing cells such as mesenchymal stem cells and methods of using embodiments of the cell culture medium for expanding cell populations such as mesenchymal stem cells while maintaining a pluripotent phenotype and methods of inducing chondrogenesis and osteogenesis of mesenchymal stem cells by admixing differentiation factors into embodiments of the cell culture medium.

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.

The present invention pertains inter alia to novel efficient methods for culturing mesenchymal stem (stromal) cells (MSCs), wherein the MSCs have maintained and/or enhanced multipotency and/or maintain and/or enhanced immunomodulatory potential. The invention also pertains to cells obtainable by such methods, kits and compositions for carrying out the methods in accordance with the invention, and also medical applications and treatments using said cells.

A method of obtaining a neural multipotent, unipotent or somatic cell, including: i) providing a cell of a first type which is not a neural multipotent, unipotent or somatic cell; ii) increasing expression of at least one neural multipotent or unipotent gene regulator in the cell of a first type, to a level at which the at least one neural multipotent or unipotent gene regulator is capable of driving transformation of the cell of a first type into the neural multipotent, unipotent or somatic cell, wherein the at least one multipotent or unipotent gene regulator is Musashi1 (Msi1), Neurogenin 2 (Ngn2), or both Msi1 and Ngn2; and iii) placing or maintaining the cell in a neural cell culture medium and maintaining sufficient intracellular levels of the at least one multipotent or unipotent gene regulator for a sufficient period of time to allow a stable neural multipotent, unipotent or somatic cell to be obtained.

A polyrotaxane represented by Formula (1):

##STR00001##

wherein R.sup.1 is a hydrogen atom or a methyl group, m is 1 to 2000, and n is 10 to 500,

##STR00002##

is a cyclodextrin in which at least one hydroxyl group is modified with a group represented by XNH.sub.2, and X is a divalent organic group.

The invention relates to methods of preparing a bone matrix solution, a bone matrix implant, and variants thereof. The invention also relates to methods of cell culture using the same. The invention further relates to bone matrix scaffolds comprising one or more bone matrix nanofibers, methods of preparing, and methods of use thereof. The invention also relates to methods of culturing cells and promoting differentiation of stem cells using the same.

The present invention relates to a method for converting mesenchymal stem cells into endothelial cells by using specific transcription factors and, more specifically, a method for converting mesenchymal stem cells into endothelial cells by using Oct4, Nanog, Tal1, and LMO2, which are specific transcription factors. According to the present invention, the method for converting adult cells or mesenchymal stem cells, which are adult stem cells, into endothelial cells was developed by selecting two types of genes, which are less directly related to cancer induction, among cell reprogramming factors and two types of transcription factors, which are not expressed or expressed at a low level in mesenchymal stem cells, among transcription factors related to vascular development, and combining all four transcription factors. The method can be applied in the production of endothelial cells for forming regenerative tissue in tissue engineering and ischemic disease therapy.

A process for producing a bone construct, including the steps of providing a perfusion bioreactor having an inlet and an outlet; providing the perfusion bioreactor with a seeded scaffold comprising a porous scaffold seeded with mesenchymal stem cells; continuously perfusing the seeded scaffold with an osteogenic induction (differentiation) media; measuring dissolved oxygen content of the osteogenic induction media at the inlet and at the outlet to determine an oxygen uptake rate (OUR) for the seeded scaffold; measuring glucose content of the osteogenic induction media to determine a glucose consumption rate (GCR) for the seeded scaffold; and removing the seeded scaffold from the perfusion reactor as a bone construct after the ratio of the OUR to the GCR (OUR/GCR) has been determined to exceed a predetermined threshold OUR/GCR value.

Compositions and methods of transplanting cells by grafting strategies into solid organs (especially internal organs) are provided. These methods and compositions can be used to repair diseased organs or to establish models of disease states in experimental hosts. The method involves attachment onto the surface of a tissue or organ, a patch graft, a bandaid-like covering, containing epithelial cells with supporting early lineage stage mesenchymal cells. The cells are incorporated into soft gel-forming biomaterials prepared under serum-free, defined conditions comprised of nutrients, lipids, vitamins, and regulatory signals that collectively support stemness of the donor cells. The graft is covered with a biodegradable, biocompatible, bioresorbable backing used to affix the graft to the target site. The cells in the graft migrate into and throughout the tissue such that within a couple of weeks they are uniformly dispersed within the recipient (host) tissue. The mechanisms by which engraftment and integration of donor cells into the organ or tissue involve multiple membrane-associated and secreted forms of MMPs.