Production of red blood cells and platelets from stem cells

US9896660B2 · kind B2 · utility

Assignees

• BOSTON MEDICAL CENTER CORPORATION · US
• TRUSTEES OF BOSTON UNIVERSITY · US

Inventors

• George J. Murphy · Boston, US
• David H. Sherr · Dedham, US
• Sarah S. Rozelle · Brookline, US
• Brenden W. Smith · East Greenwich, US

Key dates

• Filing date: Aug 15, 2013
• Grant date: Feb 20, 2018
• Expiry date: Aug 15, 2033

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2500/10
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

This disclosure provides methods of making a megakaryocyte-erythroid progenitor cell (MEP), comprising differentiating a MEP precursor cell into a MEP in culture in the presence of an aryl hydrocarbon receptor (AhR) modulator. In some embodiments the AhR modulator is an AhR antagonist. In some embodiments the AhR modulator is an AhR agonist. In some embodiments the methods comprise culturing MEP precursor cells in the presence of an AHR antagonist and then culturing MEP precursor cells in the presence of an AHR agonist. In some embodiments the stem cell is a pluripotent stem cell. In some embodiments the MEP co-expresses CD41 and CD235. In some embodiments the number of MEPs produced in the culture increases exponentially. Methods of making a red blood cell (RBC) by culturing a MEP in the presence of an AhR modulator are also provided. Methods of making a megakaryocyte and/or a platelet, comprising culturing a MEP in the presence of an AhR modulator are also provided. In some embodiments the AhR modulator is an AhR antagonist. This disclosure also provides compositions comprising at least 1 million MEPs per ml and compositions in which at least 50% of the cells are MEPs, among othe…