干细胞
移植
外周血单个核细胞
免疫学
生物
分子生物学
化学
医学
体外
细胞生物学
内科学
生物化学
作者
Stanley Chaleff,Mario Otto,Raymond Barfield,Thasia Leimig,Rekha Iyengar,Jérôme C. Martin,M. Holiday,James Houston,Terrence L. Geiger,Volker Huppert,Rupert Handgretinger
出处
期刊:Cytotherapy
[Elsevier]
日期:2007-01-01
卷期号:9 (8): 746-754
被引量:90
标识
DOI:10.1080/14653240701644000
摘要
Background We sought to develop a method for the clinical large-scale depletion of αβ T lymphocytes from mobilized peripheral stem cells, which would allow the allogeneic transplantation of a graft enriched for stem cells, natural killer (NK) cells and γδ T lymphocytes. Methods Therefore, we obtained mononuclear cells from either mobilized or non-mobilized healthy adult volunteer donors and incubated the cells with a biotinylated anti-αβ T-cell Ab and subsequently with an anti-biotin Ab conjugated with magnetic microbeads. The depletion was then performed using a CliniMACS® device. Results The median T-cell depletion was 3.9 log (range 3.5–4.1 log). The recovery of the γδ and NK cells was 92% and 80%, respectively. The recovery of CD34+ stem cells from the mobilized donors was 66%. Discussion This method had no negative influence on the in vitro colony formation of stem cells, and transplantation of αβ-depleted cells into NOD-SCID IL-2 common gamma chain knockout (NOD-scid IL2r null) mice resulted in a rapid engraftment of human myeloid and lymphoid cells. This method will allow large-scale depletion of αβ T cells from mobilized peripheral blood in clinical trials. We sought to develop a method for the clinical large-scale depletion of αβ T lymphocytes from mobilized peripheral stem cells, which would allow the allogeneic transplantation of a graft enriched for stem cells, natural killer (NK) cells and γδ T lymphocytes. Therefore, we obtained mononuclear cells from either mobilized or non-mobilized healthy adult volunteer donors and incubated the cells with a biotinylated anti-αβ T-cell Ab and subsequently with an anti-biotin Ab conjugated with magnetic microbeads. The depletion was then performed using a CliniMACS® device. The median T-cell depletion was 3.9 log (range 3.5–4.1 log). The recovery of the γδ and NK cells was 92% and 80%, respectively. The recovery of CD34+ stem cells from the mobilized donors was 66%. This method had no negative influence on the in vitro colony formation of stem cells, and transplantation of αβ-depleted cells into NOD-SCID IL-2 common gamma chain knockout (NOD-scid IL2r null) mice resulted in a rapid engraftment of human myeloid and lymphoid cells. This method will allow large-scale depletion of αβ T cells from mobilized peripheral blood in clinical trials.
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