Abstract: The development of the method of the invention enables the efficient and reproducible production of genetically modified GMP-grade human macrophages. The inventors have described the effects of the method described on cell viability and efficiency of introduction of genetic material into macrophages. Unlike previous methods of introducing genetic material into macrophages, excellent conditions are demonstrated which produce efficient transgene expression, without compromising cell viability. Critically, the method of the invention does not use virus to introduce genetic material, is efficacious on mature cells, are functional with in vitro assay and in vivo transfer in a liver disease model and complies with practices compatible with manufacture and delivery of these cells to patients.

Abstract: The improved 4-5 day, optionally 3-5 day GMP-compliant in-vitro method enables the production of macrophages from monocytes that benefits from a shorter cell culture time, fewer interventions whilst maintaining the desired characteristics of the human macrophages. The present invention describes a method wherein the monocytes are cultured in medium comprising one or more growth actors to stimulate macrophages with a pro-regenerative phenotype. The method described herein is xeno-free, serum-free and GMP compliant. In addition, further disclosed are macrophages produced according to the present invention and the use of said macrophages in the treatment of liver diseases, such as liver cirrhosis.

Abstract: The present invention relates to a method of improving the viability of macrophages subjected to cryopreservation, particularly for macrophages which are to be used in therapy, wherein the method comprises a step of maintaining the macrophages at a temperature of 2-12° C. for at least 30 minutes during either freezing or thawing procedures. Following the holding step during cooling, a cooling rate of 1 to 5° C. is used until the macrophages in a medium are frozen. For thawing the macrophages, a warming rate of 1 to 5° C. per minute is used until a temperature of 35-37° C. is reached. The present invention further relates to the cryopreserved macrophages, and the thawed macrophages produced by such methods. The technique may provide macrophages that are GMP-compliant and have a viability of at least 60%.

Abstract: The present invention relates to an agent for increasing mononuclear cell number, and/or inducing a pro-restorative phenotype in mononuclear cells for use in the treatment of a lung disease associated with dysfunctional neutrophilic inflammation, particularly wherein the agent is CSF1 and the lung disease is acute respiratory distress syndrome (ARDS).

Abstract: The present invention relates to alternatively activated macrophages (AAMs) for use in the treatment of liver injury and methods of treating and preventing liver injury using AAMs.

Abstract: The present invention relate to autologous isolated unpolarized human macrophages for use in the treatment of liver disease and macrophages for use in a method of treating fibrosis in a human in need thereof.

Abstract: The present invention relates to alternatively activated macrophages (AAMs) for use in the treatment of liver injury and methods of treating and preventing liver injury using AAMs.

Abstract: The present invention relates to compositions of matter and methods of using the same in enhancing regeneration or restoring function of an injured liver. The compositions of matter are useful in the treatment of hepatic disorders, for example, in the prevention and/or treatment of acute or chronic liver disease or as a supportive therapy to improve the outcomes following liver resection or liver transplantation.

Abstract: The present invention provides of compositions of matter comprising a CSF-1 fusion protein and methods of using the same in enhancing regeneration or restoring function of an injured liver. The compositions of matter are useful in the treatment of hepatic disorders, for example, in the prevention and/or treatment of liver disease and to improve outcomes following liver surgery.