Manipulation of immune system via immortal bone marrow stem cells.
Extensive amplification of hematopoietic stem cells (HSCs) and their multipotent primitive progenitors (MPPs) in culture would greatly benefit not only clinical transplantation but also provide a potential tool to manipulate all cellular lineages derived from these cells for gene therapy and experimental purposes. Here, we demonstrate that mouse bone marrow cultures containing cells engineered to over-express NUP98-HOXB4 fusion protein support self-renewal of physiologically normal HSC and MPP for several weeks leading practically to their unlimited expansion. This allows time consuming and cumulative in vitro experimental manipulations without sacrificing their ability to differentiate in vivo or in vitro to any hematopoietic lineage.
Ruedl
Christiane
C
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore. ruedl@ntu.edu.sg
Khameneh
Hanif Javanmard
HJ
Karjalainen
Klaus
K
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005818:Genetic Engineering / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007107:Immune System; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic
C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D028861:Nuclear Pore Complex Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C093350:nuclear pore complex protein 98