Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US5770417

Title:Three-dimensional fibrous scaffold containing attached cells for producing vascularized tissue in vivo
Inventors:Vacanti, Joseph P.; Winchester, MA, USA
Langer, Robert S.; Somerville, MA, USA
Summary:Described herein is an artificial matrix for the controlled cell growth of functional organ tissue. The invention relates to a three-dimensional cell-scaffold composed of hollow or solid fibers of a biocompatible, synthetic polymer which is either biodegradable or non-biodegradable, and in which the fibers of the scaffold may have a branched configuration extending outwardly from a central stem over which nutrients and gases are diffused through a mass of cells attached to the fibers, such that the diffusion provides a free exchange of nutrients, gases and waste to and from the cells proliferating throughout the scaffold in an amount effective to maintain cell viability throughout the scaffold in the absence of vascularization. Further disclosed are methods by which cells derived from vascularized organ tissue are attached in vitro to the surface of the fibers uniformly throughout the scaffold in an amount effective to produce functional vascularized organ tissue in vivo, such that the cells are grown on the scaffold in a nutrient solution in vitro to form the cell-scaffold composition which is implanted in a host at a location having adequate vascularization to allow growth of blood vessels into the cell-scaffold composition. Also described are growth factors, compounds stimulating angiogenesis and immunomodulators which may be incorporated into the method. Therapeutic applications in the chimeric neomorphogenesis of organs by controlled cellular implantation are included. This invention represents a continuation of other applications filed by the same assignee and inventors.
Abstract:A cell-scaffold composition is prepared in vitro for implanting to produce functional organ tissue in vivo. The scaffold is three-dimensional and is composed of hollow or solid fibers of a biocompatible, synthetic polymer which is biodegradable or non-biodegradable. The fibers of the scaffold may have a branched configuration extending outwardly from a central stem. Fibers of the scaffold are spaced apart such that the maximum distance over which diffusion of nutrients and gases must occur through a mass of cells attached to the fibers is between 200 and 300 microns. The diffusion provides free exchange of nutrients, gases and waste to and from cells proliferating throughout the scaffold in an amount effective to maintain cell viability throughout the scaffold in the absence of vascularization. Cells derived from vascularized organ tissue are attached in vitro to the surface of the fibers uniformly throughout the scaffold in an amount effective to produce functional vascularized organ tissue in vivo, the cells are grown on the scaffold in a nutrient solution in vitro to form the cell-scaffold composition which is implanted in a host at a location having adequate vascularization to allow growth of blood vessels into the cell-scaffold composition. Growth factors, compounds stimulating angiogenesis and immunomodulators may be provided in the cell-scaffold composition and the fibers may have a coating to enhance cell attachment. Combinations of cell-scaffold compositions containing different cell populations may be implanted.
US Patent Website:Click Here for Full Text of Patent
Title Number:US5770417
Application Number:US1994000203705
Date Filed:28/02/1994
Date Published:23/06/1998
Assignee:Massachusetts Institute of Technology Children's Medical Center Corporation, Cambridge, MA, USA


 
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