Abstract: Described are a micro punch cutting tool and associated method that can be used under a microscope to accurately excise a targeted piece of material on a micron or millimeter scale. An example device for targeted material excision from a tissue sample includes a support defining an opening and providing a region below the opening for positioning a tissue sample. A tissue stabilizer is receivable in the opening and defines a shape that complements a shape of the support. A cutting tool assembly receivable in the tissue stabilizer includes a hollow cutter having a bore and is movable relative to the tissue stabilizer to cause the cutter to excise material from the tissue sample when the tissue sample is positioned below the opening of the support. Movement of the cutting tool assembly is guided by a helical groove in the tissue stabilizer engaging a protrusion of the cutting tool assembly.

Abstract: An ex-vivo method of treating myeloablation of hematopoietic stem and progenitor cells, particularly myeloablation due to ionizing radiation is disclosed. An ex-vivo method of restoring a depleted population of rapidly proliferating hematopoietic stem cells is also disclosed. The methods comprise co-culturing resistant hematopoietic stem cells in a culture medium comprising a monolayer of endothelial cells and various cytokines. Bone marrow stem cells harvested from animals exposed to 1050 cGy were incapable of providing hematopoietic recovery in secondary irradiated recipients. Bone marrow stem cells harvested from animals exposed to 1050 cGy and then co-cultured×10 days with endothelial cell monolayers showed complete recovery of hematopoietic repopulating capacity which was equivalent to normal BM stem cells.

Abstract: Compositions and methods disclosed herein capitalize on the discovery that rejection of a tissue graft can be inhibited using a CD40:CD154 binding interrupter, either alone or in combination with another immunomodulator or immunosuppressor. An advantageous, synergistic combination includes a CD40:CD154 binding interrupter and a CD28 signaling interrupter. An exemplary CD40:CD154 binding interrupter is an anti-CD154 monoclonal antibody, such as an antibody having the antigen-specific binding characteristics of the 5c8 monoclonal antibody. An exemplary CD28 signaling interrupter is a CTLA4-Ig fusion protein. The disclosed compositions and methods unexpectedly can be used to prolong survival of grafted tissue in a recipient host, to reverse acute graft rejection, and to attenuate immunological consequences of the failure of grafted tissue.

Abstract: A transgenic animal, whose germ cells and somatic cells contain a transgene including a DNA sequence encoding a CD28 ligand and a tissue-specific promoter operably linked to the DNA sequence, wherein the tissue-specific promoter effects expression of the CD28 ligand in cells of a specific tissue of the animal is disclosed. This animal serves as a transgenic model for specific autoimmune diseases.