Methods and compositions for improved clinical outcomes for trauma patients receiving whole blood transfusion. Methods and compositions for improved clinical outcomes for blood transfusions for cancer patients are also provided.

The application relates to the use of loaded red blood cells (e.g. “RBCs”, “red cells” or “erythrocytes”) or red blood cell precursors to produce red cell extracellular vesicles (RCEVs) containing cargos, including cargos comprising biologically active ingredients. Notable red cell precursors include hematopoietic stem cells (HSCs), induced pluripotent stem cells (iPSCs), and reticulocytes. The cargo may comprise nucleic acids, proteins, small molecules, or components of a gene editing system, including CRISPR/Cas9. The RCEVs may be used to treat of diseases and disorders including autoimmune disorders, cancers, cardiovascular diseases, gastrointestinal diseases, genetic disorders, or inflammatory diseases. The RCEVs may also be used to carry antigens and or immune modulator, for use in eliciting immune or immune tolerance responses. Also provided are methods for producing cargo loaded RCEVs (CLRCEVs) by first loading cargo into red cells and then by vesiculating the cargo loaded red cells to yield the CLRCEVs.

The application relates to the use of loaded red blood cells (e.g. “RBCs”, “red cells” or “erythrocytes”) or red blood cell precursors to produce red cell extracellular vesicles (RCEVs) containing cargos, including cargos comprising biologically active ingredients. Notable red cell precursors include hematopoietic stem cells (HSCs), induced pluripotent stem cells (iPSCs), and reticulocytes. The cargo may comprise nucleic acids, proteins, small molecules, or components of a gene editing system, including CRISPR/Cas9. The RCEVs may be used to treat of diseases and disorders including autoimmune disorders, cancers, cardiovascular diseases, gastrointestinal diseases, genetic disorders, or inflammatory diseases. The RCEVs may also be used to carry antigens and or immune modulator, for use in eliciting immune or immune tolerance responses. Also provided are methods for producing cargo loaded RCEVs (CLRCEVs) by first loading cargo into red cells and then by vesiculating the cargo loaded red cells to yield the CLRCEVs.

Methods for testing a red blood cell (RBC) unit for release for transfusion into a subject are described. The methods allow management of the blood supply by assessing the viability of an RBC unit by its levels of dicarboxylic fatty acids (DFA). The methods include testing an RBC sample from an RBC unit for levels of DFA and discarding the RBC unit or releasing or not releasing the RBC unit for transfusion based on the results.

Methods for testing a red blood cell (RBC) unit for release for transfusion into a subject are described. The methods allow management of the blood supply by assessing the viability of an RBC unit by its levels of dicarboxylic fatty acids (DFA). The methods include testing an RBC sample from an RBC unit for levels of DFA and discarding the RBC unit or releasing or not releasing the RBC unit for transfusion based on the results.

Compositions, containers and kits for low temperature storage of a specified quantity of packed red blood cells (RBCs) include L-camitine, HES and blood plasma proteins. Methods of storing a packed RBC blood product, transfusing a packed RBC blood product into a subject, and treating anemia, ischemia, hypoxia, a hemoglobin disorder, or a hematopoietic disorder in a subject (e.g., a human) include the compositions, containers, kits and blood products.

Compositions, containers and kits for low temperature storage of a specified quantity of packed red blood cells (RBCs) include L-camitine, HES and blood plasma proteins. Methods of storing a packed RBC blood product, transfusing a packed RBC blood product into a subject, and treating anemia, ischemia, hypoxia, a hemoglobin disorder, or a hematopoietic disorder in a subject (e.g., a human) include the compositions, containers, kits and blood products.

The present invention relates to an active ingredient of an erythrocytes-containing composition, an erythrocytes-containing composition comprising said active ingredient, and a method of treatment of a human or animal being suffering from and/or threatened by blood loss or a blood-formation disorder.

The present invention relates to an active ingredient of an erythrocytes-containing composition, an erythrocytes-containing composition comprising said active ingredient, and a method of treatment of a human or animal being suffering from and/or threatened by blood loss or a blood-formation disorder.

Methods for making hemoglobin based blood substitute preparations and hemoglobin based blood substitute preparations. The methods involve preparing a low purity erythrocyte protein fraction comprising hemoglobin protein and endogenous non-hemoglobin protein complement, and chemically modifying the proteins in the protein fraction to form a cross-linked hemoglobin containing blood substitute preparation. The low purity erythrocyte protein preparation can contain from at least about 0.2% (mole/mole) up to about 20% (mole/mole) endogenous non-hemoglobin protein complement. At least about 90% (mole/mole) of the hemoglobin proteins can be cross-linked, so that the average molecular mass of cross-linked proteins comprising hemoglobin protein molecules in the preparation is at least about 300 kDa. The preparations can be used to prepare finished blood substitute formulations for in-vivo and ex-vivo use.