The present invention pertains to the development of biologically derived extracellular matrices (ECM) derived from decellularized pleura tissue. Such matrices are useful in many clinical and therapeutic applications, including the repair, reconstruction, sealing, or joining of tissue, tendons, bones, and/or ligaments. In addition, the present invention features methods of making a biologically derived ECM derived from decellularized pleura tissue. The invention further features laminated ECM matrices.

A multi-step stabilization method for connective tissue is described. Stabilized tissues can exhibit increased resistance to degradation due to enzyme activity, fatigue and storage. The multi-step method includes a first step during which the tissue can be incubated with a glycosaminoglycanase inhibitor such as a sulfated oligosaccharide, one example of which being neomycin, a second step during which the tissue can be incubated with a crosslink activator such as a carbodiimide crosslink activator and/or a crosslinking agent such as a heterobifunctional crosslinking agent and/or a phenolic compound such as a tannin, examples of which include tannic acid and pentagalloylglucose, and a third step during which the tissue can be incubated with a second crosslink activator that can be the same or different as the first crosslink activator.

A cardiothoracic construct fabricated from human birth tissue comprising at least one cross-linked amniotic membrane, or at least one cross-linked chorionic membrane, or at least one amniotic membrane, or at least one chorionic membrane, or any combination thereof wherein the membrane(s) is/are treated with at least one alcohol composition followed by terminal sterilization is provided. Methods of processing a membrane to form a cardiothoracic construct and methods of preventing adhesion after a cardiac surgical procedure are also provided.

This invention provides a system for efficiently producing differentiated cells from pluripotent cells, such as human embryonic stem cells. Rather than permitting the cells to form embryoid bodies according to established techniques, differentiation is effected directly in monolayer culture on a suitable solid surface. The cells are either plated directly onto a differentiation-promoting surface, or grown initially on the solid surface in the absence of feeder cells and then exchanged into a medium that assists in the differentiation process. The solid surface and the culture medium can be chosen to direct differentiation down a particular pathway, generating a cell population that is remarkably uniform. The methodology is well adapted to bulk production of committed precursor and terminally differentiated cells for use in drug screening or regenerative medicine.

Hybrid nuclease molecules and methods for treating an immune-related disease or disorder in a mammal, and a pharmaceutical composition for treating an immune-related disease in a mammal.

The invention relates to a method for inducing pluripotent stem cells, wherein a mammalian cell is contacted with a compound characterized by a general formula 1 wherein R.sup.1 is (CH.sub.2).sub.mE, with E being CCH or CN and m being 0, 1, or 2, and R.sup.2 is selected from F, CI, Br, OR.sup.3 and R.sup.3, with R.sup.3 being selected from H, (CH.sub.yF.sub.2-y).sub.n CH.sub.XF.sub.3-X, with n=0 or 1. The invention further relates to stem cells obtained by the method of the invention, and culture media comprising the compound of the invention.

In some embodiments, methods for improving the survival of pancreatic β-cell progenitors in culture are provided. Such methods may include contacting a population of pancreatic progenitor cells with an amino acid (aa) sequence comprising IKVAV (SEQ ID NO:1). In other embodiments, methods for (i) verifying the establishment of a population of pancreatic progenitor or stem cells and (ii) methods for generating or establishing a population of pancreatic endocrine progenitor cells in vitro are provided.

The present invention provides novel methods for improving the efficiency of artificial activation of unfertilized mammalian oocytes by reducing the intracellular concentration of Zn.sup.2+ in the oocyte. The methods of the invention may additionally comprise a preceding step of increasing the intracellular concentration of Ca.sup.2+ in the oocyte prior to reduction of the intracellular Zn.sup.2+ concentration. The invention further provides unfertilized oocytes activated by the disclosed methods and viable mammalian animals produced from unfertilized oocytes activated by the disclosed methods.

Synthetic surfaces suitable for culturing stem cell derived cardiomyocytes contain acrylate polymers formed from one or more acrylate monomers. The acrylate surfaces, in many cases, are suitable for culturing stem cell derived cardiomyocytes in chemically defined media.

The invention relates to an in vitro method to generate T cell progenitors, comprising the step of culturing CD34+ cells in a medium containing TNF-alpha and/or an antagonist of the Aryl hydro-carbon/Dioxin receptor, in particular StemRegenin 1 (SR1), in presence of a Notch ligand and optionally a fibronectin fragment.