Optimization of retroviral-mediated gene transfer to human NOD/SCID mouse repopulating cord blood cells through a systematic analysis of protocol variables

Hennemann, B.; Conneally, Eibhlin; Pawliuk, Robert; Leboulch, Philippe; Rose-John, Stefan; Reid, Dianne; Chuo, Jean Y.; Humphries, R. Keith; Eaves, Connie J.

doi:10.1016/s0301-472x(99)00021-1

Cited by 99 publications

(67 citation statements)

References 36 publications

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“…10 Repopulation of mice with human cells and detection of the specific lineages produced were determined from FACS analyses of 2 Â 10 4 PI À cells in BM aspirates after lysis of the RBCs with ammonium chloride (StemCell Technologies, Vancouver, BC, Canada) and staining with directly labeled antibodies against 'lineage' (lin) human antigens as described. 7 Reverse transcriptase (RT)-PCR analyses RNA was extracted from 10 4 human GFP þ cells isolated by FACS from BM aspirates obtained from the transplanted mice.…”

Section: Flow Cytometrymentioning

confidence: 99%

BCR-ABL-transduced human cord blood cells produce abnormal populations in immunodeficient mice

et al. 2005

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In this study, we describe the successful use of a gene transfer approach to demonstrate the ability of forced BCR-ABL expression to deregulate the growth and differentiation of primitive naïve human hematopoietic cells after their transplantation into immunodeficient mice. Human CD34 þ cord blood cells were exposed to an MSCV retrovirus containing a BCR-ABL-IRES-GFP (P210) cassette and then injected immediately into sublethally irradiated nonobese diabetic-severe combined immunodeficiency (NOD/SCID) or NOD/SCID-b2microglobulin À/À mice. P210-and control-transduced (GFP þ ) human hematopoietic cells were produced in the bone marrow of the mice at similar levels until termination of the experiments 5-6 months later. However, the P210-transduced cells produced a markedly different spectrum of progeny, with an increased ratio of myeloid to B-lymphoid cells and a frequently prolonged increase in erythroid and megakaryocytic cells. After 5 months, several of the mice transplanted with P210-transduced cells developed an increased WBC count and/or splenomegaly due to an expansion of the human GFP þ population. These findings demonstrate that forced expression of BCR-ABL in primitive transplantable human hematopoietic cells is sufficient to cause a rapid and persistent deregulation of their growth and differentiation in vivo with occasional evidence after several months of progression to an early stage of disease.

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Section: Flow Cytometrymentioning

confidence: 99%

BCR-ABL-transduced human cord blood cells produce abnormal populations in immunodeficient mice

et al. 2005

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“…[37][38][39][40][41][42][43][44] Unfortunately, maneuvers for improving transduction in vitro, such as prolonging exposure to viral vectors, stimulating cell proliferation, or culturing on stromal cells, affect the phenotypic features of progenitor cells in undesirable ways. 45,46 To explore the concept of systemic gene delivery into areas of angiogenesis, we sought to use cellular vehicles naturally endowed with angiogiogenic tropism.…”

Section: Introductionmentioning

confidence: 99%

Genetically modified CD34+ cells as cellular vehicles for gene delivery into areas of angiogenesis in a rhesus model

Gómez-Navarro¹,

Contreras²,

Arafat³

et al. 2000

Gene Ther

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To develop a cellular vehicle able to reach systemically disseminated areas of angiogenesis, we sought to exploit the natural tropism of circulating endothelial progenitor cells (EPCs). Primate CD34 + EPCs were genetically modified with high efficiency and minimal toxicity using a non-replicative herpes virus vector. These EPCs localized in a skin autograft model of angiogenesis in rhesus monkeys, and sustained the expression of a reporter gene for several weeks while circulating in the blood. In animals infused with autologous CD34+ EPCs transduced with a thymidine kinase-encoding herpes virus, skin autografts and subcutaneous Matrigel pel-

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“…Whilst the earliest trials suffered from poor transduction of human repopulating stem cells, 24,25 recent developments in HSC-transduction and in ex vivo manipulation of HSCs are likely to overcome this difficulty. [26][27][28] Indeed, a recent report of MDR-1-transduced cells in human patients highlights improvements in this regard. 10 Leukemia Ironically, at the same time as MDR-1-mediated genetic chemoprotection in humans appears technically feasible, a new problem has arisen as a result of studies in mice.…”

Section: Discussionmentioning

confidence: 99%

Retroviral transfer and expression of human MDR-1 in a murine haemopoietic stem cell line does not alter factor dependence, growth or differentiation characteristics

et al. 2002

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In view of the recent report of a myeloproliferative syndrome in mice that had received an MDR-1-transduced haemopoietic graft, we have investigated the potential effects of MDR-1 expression on primitive haemopoietic cell growth and differentiation. Retroviral gene transfer was used to achieve exogenous expression of either MDR-1 or truncated nerve growth factor receptor (tNGFR) in the multipotent murine haemopoietic progenitor cell line, FDCP-mix. Following gene transfer, clonal lines were derived and FACS analysis confirmed appropriate expression of each transgene. MDR-1 (but not tNGFR) expression was associated with verapamil-sensitive rhodamine efflux and resistance to killing by etoposide. When growth factor responsiveness, proliferative capacity and differentiation capacity were examined, MDR-1 expressing FDCP-mix cells exhibited a normal phenotype and mimicked the response of tNGFR-expressing or untransduced FDCP-mix cells. Thus, in the model system we have used, MDR-1 does not perturb haemopoietic cell growth and development and our data do not support a myeloproliferative role for MDR-1.

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Optimization of retroviral-mediated gene transfer to human NOD/SCID mouse repopulating cord blood cells through a systematic analysis of protocol variables

Cited by 99 publications

References 36 publications

BCR-ABL-transduced human cord blood cells produce abnormal populations in immunodeficient mice

BCR-ABL-transduced human cord blood cells produce abnormal populations in immunodeficient mice

Genetically modified CD34+ cells as cellular vehicles for gene delivery into areas of angiogenesis in a rhesus model

Retroviral transfer and expression of human MDR-1 in a murine haemopoietic stem cell line does not alter factor dependence, growth or differentiation characteristics

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