<i>In Vivo</i> Dynamics of Human Stem Cell Repopulation in NOD/SCID Mice

Dick, John E.; Güenechea, Guillermo; Gan, Olga I.; Dorrell, Craig

doi:10.1111/j.1749-6632.2001.tb03588.x

Cited by 20 publications

(6 citation statements)

References 24 publications

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“…Numerous xenotransplantation experiments have reported the successful enrichment of human HSC activity in Lin-CD34+CD38-/lo fractions of human hematopoietic progenitors through the demonstration of long-term multipotent engraftment and successful secondary transplantation (Dick et al, 2001;McKenzie et al, 2006). In published reports, successful secondary engraftment has required primary transplantation of large numbers of cells, minimally thousands and usually many more.…”

Section: Discussionmentioning

confidence: 99%

“…McCune and colleagues used the SCID-hu mouse model to identify human HSC activity among Lin-CD34 +CD90+ cells (McCune et al, 1988;Murray et al, 1995;Peault et al, 1993). Dick and colleagues initially used SCID/beige/XID, and more recently NOD/SCID mice, to assay normal human progenitor subpopulations (Dick et al, 2001). By assessing long-term multipotent human hematopoiesis in recipients and the ability to form secondary and tertiary transplants, human HSC were found to reside in the Lin-CD34+CD38-/lo fraction of human progenitors (Bhatia et al, 1997;Cashman et al, 1997;Hogan et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Identification of a Hierarchy of Multipotent Hematopoietic Progenitors in Human Cord Blood

2007

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Mouse hematopoiesis is initiated by long-term hematopoietic stem cells (HSC) that differentiate into a series of multipotent progenitors that exhibit progressively diminished self-renewal ability. In human hematopoiesis, populations enriched for HSC activity have been identified, as have downstream lineage-committed progenitors, but multipotent progenitor activity has not been uniquely isolated. Previous reports indicate that human HSC are enriched in Lin-CD34+CD38- cord blood and bone marrow and express CD90. We demonstrate that the Lin-CD34+CD38- fraction of cord blood and bone marrow can be subdivided into three subpopulations: CD90+CD45RA-, CD90-CD45RA-, and CD90-CD45RA+. Utilizing in vivo transplantation studies and complementary in vitro assays, we demonstrate that the Lin-CD34+CD38-CD90+CD45RA- cord blood fraction contains HSC and isolate this activity to as few as 10 purified cells. Furthermore, we report the first prospective isolation of a population of candidate human multipotent progenitors, Lin-CD34+CD38-CD90-CD45RA- cord blood.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of a Hierarchy of Multipotent Hematopoietic Progenitors in Human Cord Blood

2007

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“…[35–44] These PBPC studies set the stage for the use of this approach with CB. While there is evidence of functional and phenotypic heterogeneity within the primitive haematopoietic progenitor compartment,[45–48] one concern associated with ex vivo expansion is that short-term reconstituting, lower ‘quality’ haematopoietic progenitors will be expanded at the expense of longer-term reconstituting, higher ‘quality’ haematopoietic progenitors, thereby significantly impacting the haematopoietic reserve of the graft. [49] Evidence primarily in animal models, suggest that this may occur under certain conditions.…”

Section: E Concerns Associated With Ex Vivo Expansionmentioning

confidence: 99%

Mesenchymal stem cells in ex vivo cord blood expansion

Robinson

Simmons

Yang

et al. 2011

Best Practice & Research Clinical Haematology

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Umbilical cord blood (CB) is becoming an important source of haematopoietic support for transplant patients lacking human leukocyte antigen matched donors. The ethnic diversity, relative ease of collection, ready availability as cryopreserved units from CB banks, reduced incidence and severity of graft versus host disease and tolerance of higher degrees of HLA disparity between donor and recipient, are positive attributes when compared to bone marrow or cytokine-mobilized peripheral blood. However, CB transplantation is associated with significantly delayed neutrophil and platelet engraftment and an elevated risk of graft failure. These hurdles are thought to be due, at least in part, to low total nucleated cell and CD34+ cell doses transplanted. Here, current strategies directed at improving TNC and CD34+ cell doses at transplant are discussed, with particular attention paid to the use of a mesenchymal stem cell (MSC)/CB mononuclear cell ex vivo co-culture expansion system.

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“…Non-adherent cell were removed from each flask and transferred into individual culture system with MSC conditioned medium for additional 7 days (totally 14 days), achieving approximately 12 fold increase in CD34+ cells and 12-fold increase in total nuclear cells. However, functional and phenotypic heterogeneity have been observed within primitive hematopoietic stem cells/progenitors [100][101][102][103][104]. Most MSC-UCB co-cultures were established on bone marrow MSCs with exogenously added cytokines to promote HSC proliferation; the resulting cells have been referred to as "lower quality" hematopoietic progenitors contributing to short term reconstitution [32, 103,104].…”

Section: Co-culture With Stromal Cellsmentioning

confidence: 99%

Umbilical Cord Blood Hematopoietic Stem Cell Expansion Ex Vivo

Ren¹,

Jiang²

2013

J Blood Disord Transfus 2012

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Umbilical cord blood is an attractive source of hematopoietic stem and progenitor cells in the treatment of hematologic diseases, especially in allogeneic hematopoietic cell transplantation. However, due to the low abundance of these cells, the therapeutic use of umbilical cord blood has been limited mostly to the pediatric setting. The strategies for adult umbilical cord blood transplantation have been improved, with the recent development of various approaches for expanding stem cells in vitro and enhancing their long-term homing efficiency. In this brief review, we discuss a number of strategies for stimulating the proliferation of umbilical cord blood hematopoietic stem cells in vitro, including the utility of transcription factors and growth factors (cytokine cocktails), as well as co-culturing with stromal cells. Ultimately, we make the case that improvements in umbilical cord blood stem cell expansion will be critical for enhancing transplantation engraftment efficacy and providing potential cure for hematological diseases.

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In Vivo Dynamics of Human Stem Cell Repopulation in NOD/SCID Mice

Cited by 20 publications

References 24 publications

Identification of a Hierarchy of Multipotent Hematopoietic Progenitors in Human Cord Blood

Identification of a Hierarchy of Multipotent Hematopoietic Progenitors in Human Cord Blood

Mesenchymal stem cells in ex vivo cord blood expansion

Umbilical Cord Blood Hematopoietic Stem Cell Expansion Ex Vivo

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