A method for producing a fibrin sheet containing at least one selected from the group consisting of cells and drugs in a fibrin gel, the method comprising: a step 1 of applying a fibrinogen solution containing at least one selected from the group consisting of cells and drugs and fibrinogen dropwise onto a surface of a substrate made of a gelatin hydrogel; a step 2 of adding thrombin to the fibrinogen solution on the surface of the substrate; a step 3 of placing a support film on and in contact with a top surface of the fibrinogen solution to which the thrombin has been added; a step 4 of forming a fibrin sheet containing the at least one selected from the group consisting of cells and drugs in a fibrin gel between the substrate and the support film by a reaction between the fibrinogen and the thrombin; and a step 5 of melting the substrate at a temperature not lower than a melting temperature of the gelatin hydrogel to separate, from the substrate, the fibrin sheet supported by the support film.

Methods are described for treating a heart disease, comprising suspending c) mesenchymal stem cells in either a) a fibrinogen solution or b) a thrombin solution, thereby obtaining a cell suspension, and directly spraying the cell suspension on a disease site substantially at the same time with the other of a) the fibrinogen solution or b) the thrombin solution that is not used in the suspending.

Provided are methods and devices for dissolving solid protein compositions, such as solid compositions comprising fibrinogen, in an aqueous solvent. The methods comprise use of a closed container containing a volume of solid fibrinogen composition and a head space wherein the pressure within the headspace is sub-atmospheric. Aqueous solvent is introduced into the container while maintain the sub-atmospheric pressure, and subsequent to addition of the solvent, the size of the headspace is decreased to bring the pressure to atmospheric pressure. The devices are suitable for use in the disclosed method.

Provided are methods and devices for dissolving solid protein compositions, such as solid compositions comprising fibrinogen, in an aqueous solvent. The methods comprise use of a closed container containing a volume of solid fibrinogen composition and a head space wherein the pressure within the headspace is sub-atmospheric. Aqueous solvent is introduced into the container while maintain the sub-atmospheric pressure, and subsequent to addition of the solvent, the size of the headspace is decreased to bring the pressure to atmospheric pressure. The devices are suitable for use in the disclosed method.

Provided are modified therapeutic cells that overexpress an immune checkpoint ligand such as PD-L1, CD155, CD112, FGL1, galectin-9, CD47, B7H3 and B7H4, while expressing one or more Major Histocompatibility Complex (MHC) molecules. Also provided are methods of treatment using the modified therapeutic cells.

The present invention relates to mutated factor (FX) polypeptides and uses thereof for the treatment of haemophilia. In particular, the present invention relates to a mutated factor X (FX) polypeptide wherein the heavy chain comprises at least one mutation selected from the group consisting of: —the mutation which consists of the substitution of the glutamic acid residue (E) at position 255 of Seq. ID No. 1 by a glutamine residue (Q), an asparagine residue (N), a serine residue (S), an alanine residue (A), or a tyrosine residue (Y); —the mutation which consists of the substitution of the glutamic acid residue (E) at position 256 of Seq. ID No. 1 by a glutamine residue (Q); and —the mutation which consists of the substitution of the glutamic acid residue (E) at position 258 of Seq. ID No. 1 by a glutamine residue (Q);

The present invention relates to mutated factor (FX) polypeptides and uses thereof for the treatment of haemophilia. In particular, the present invention relates to a mutated factor X (FX) polypeptide wherein the heavy chain comprises at least one mutation selected from the group consisting of: —the mutation which consists of the substitution of the glutamic acid residue (E) at position 255 of Seq. ID No. 1 by a glutamine residue (Q), an asparagine residue (N), a serine residue (S), an alanine residue (A), or a tyrosine residue (Y); —the mutation which consists of the substitution of the glutamic acid residue (E) at position 256 of Seq. ID No. 1 by a glutamine residue (Q); and —the mutation which consists of the substitution of the glutamic acid residue (E) at position 258 of Seq. ID No. 1 by a glutamine residue (Q);

The present invention provides a gel formed of fibrin and a molecule generated by thrombin treatment of a chimeric protein that comprises a fibrinogen fragment capable of binding to fibrinogen upon thrombin treatment and a laminin fragment having integrin-binding activity, and optionally further comprises a protein having growth factor-binding activity. The gel of the present invention is suitable as a gel substrate that has properties of the basement membrane and can be used in medical applications.

The present invention provides a gel formed of fibrin and a molecule generated by thrombin treatment of a chimeric protein that comprises a fibrinogen fragment capable of binding to fibrinogen upon thrombin treatment and a laminin fragment having integrin-binding activity, and optionally further comprises a protein having growth factor-binding activity. The gel of the present invention is suitable as a gel substrate that has properties of the basement membrane and can be used in medical applications.

Recombinant Fibrinogen C Domain Containing 1 (rFibcd1) proteins and methods for using the same in the treatment of muscle atrophy are provided as are vectors, host cells, pharmaceutical compositions and modified RNA molecules encoding the rFibcd1 proteins.