The present invention provides a method for producing human immortalized megakaryocytes and / or human immortalized
megakaryocyte progenitor cells and / or human
megakaryocyte cell lines (102) from adult CD34 + HSPC (100) capable of maturation into functional megakaryocytes (103) producing functional platelets (104), said method comprising at least the steps of: producing functional platelets (104) by transduction, in particular lentiviral (LV) transduction; an
expression cassette comprising at least one
gene is introduced into the CD34 + HSPC (100) to effectuate forced expression of the at least one
gene wherein the transduced CD34 + HSPC (100) is configured to express at least one
gene from the HOXL subclass of the ANTP homologous cassette family and / or the TALE homologous cassette family upon activator-induced expression, and constitutively expressing at least one anti-
apoptotic gene from the BCL2 family wherein the transduced CD34 + HSPC (100) is immortalized by expression of the at least one gene from the ANTP homologous cassette family and / or the HOXL subclass of the TALE homologous cassette family, preferably wherein the at least one gene from the HOXL subclass comprises a combination of one of the HOXB8, HOXA7, HOXA10 or HOXB4 genes and at least one of the MEIS1, MEIS2, MEIS3, PBX1, PBX2, PBX3 and / or PBX4 genes, and the at least one anti-
apoptosis gene from the BCL2 family comprises BCL2L1 or BCL2L2. The invention further provides a method of producing functional platelets by using the immortalized megakaryocytes and / or immortalized
megakaryocyte progenitor cells and / or immortalized megakaryocyte
cell lines obtained by the above method. Further, the present invention provides a pharmaceutical composition comprising functional platelets obtained by the above method and its therapeutic use.