Retrovirus integration into the host cell genome occurs most efficiently in replicating cells. In agreement with this notion, it was observed that the efficiency with which hemopoietic stem cells (HSC) can be transduced is greatly enhanced when the hemopoietic growth factor (HGF) interleukin 3 (IL-3) is added to co-cultures of bone marrow cells with retrovirus-producing cells. The HGF IL-6, which enhances the IL-3-induced formation of blast cell colonies in vitro, is also believed to improve the transduction of HSC. Because IL-6 can be produced by a number of different cell types, we investigated whether IL-6 was present in the culture supernatant of retrovirus packaging cells and bone marrow cells. We found that the six retrovirus packaging cells tested produced large amounts of IL-6. Bone marrow cells cultured with IL-1 alpha and IL-3 also make IL-6, and, following co-cultivation of both cell types, the concentration of IL-6 in the medium is even up to 10-fold higher than the sum of the concentrations obtained when both are cultured separately. Considering that IL-6 is produced in large amounts during co-cultivations, we believe that its effect on the transduction of HSC cannot be measured by adding extra growth factor to the co-culture medium.
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http://dx.doi.org/10.1089/hum.1991.2.4-301 | DOI Listing |
Tissue Eng Regen Med
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Department of Orthopaedics, Dongguk University Ilsan Hospital, Dongguk-Ro 27, Goyang, Republic of Korea.
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Facultad de Ciencias Veterinarias. Cátedra de Enfermedades Infecciosas, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
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View Article and Find Full Text PDFBlood
January 2025
1Princess Margaret Cancer Centre, University Health Network; Toronto, ON M5G 1L7, Canada 14Department of Molecular Genetics, University of Toronto; Toronto, ON, Canada, Canada.
Leukemic stem cells (LSCs) fuel acute myeloid leukemia (AML) growth and relapse, but therapies tailored towards eradicating LSCs without harming normal hematopoietic stem cells (HSCs) are lacking. FLT3 is considered an important therapeutic target due to frequent mutation in AML and association with relapse. However, there has been limited clinical success with FLT3 drug targeting, suggesting either that FLT3 is not a vulnerability in LSC, or that more potent inhibition is required, a scenario where HSC toxicity could become limiting.
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