In vitro expansion of hematopoietic stem cells by recombinant TAT-HOXB4 protein
| Autor: | Pamela Austin, Evert Kroon, Nathalie Beslu, R. Keith Humphries, Guy Sauvageau, Jana Krosl |
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| Rok vydání: | 2003 |
| Předmět: |
Recombinant Fusion Proteins
medicine.medical_treatment Genetic Vectors General Biochemistry Genetics and Molecular Biology Mice Retrovirus In vivo medicine Animals Humans Homeodomain Proteins biology Growth factor Gene Transfer Techniques General Medicine Hematopoietic Stem Cells biology.organism_classification Virology In vitro Cell biology Transplantation Haematopoiesis Retroviridae medicine.anatomical_structure Gene Products tat Bone marrow Stem cell Cell Division Transcription Factors |
| Zdroj: | Nature Medicine. 9:1428-1432 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | Hematopoietic stem cells (HSCs) can self-renew extensively after transplantation. The conditions supporting their in vitro expansion are still being defined. Retroviral overexpression of the human homeobox B4 (HOXB4) gene in mouse bone marrow cells enables over 40-fold expansion of HSCs in vitro. To circumvent the requirement for retroviral infection, we used recombinant human TAT-HOXB4 protein carrying the protein transduction domain of the HIV transactivating protein (TAT) as a potential growth factor for stem cells. HSCs exposed to TAT-HOXB4 for 4 d expanded by about four- to sixfold and were 8-20 times more numerous than HSCs in control cultures, indicating that HSC expansion induced by TAT-HOXB4 was comparable to that induced by the human HOXB4 retrovirus during a similar period of observation. Our results also show that TAT-HOXB4-expanded HSC populations retain their normal in vivo potential for differentiation and long-term repopulation. It is thus feasible to exploit recombinant HOXB4 protein for rapid and significant ex vivo expansion of normal HSCs. |
| Databáze: | OpenAIRE |
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