Evaluation of ex vivo expansion and engraftment in NOD-SCID mice of umbilical cord blood CD34+ cells using the DIDECO ‘Pluricell System’

Astori, Giuseppe; Adami, Valentina; Mambrini, Giovanni; Bigi, Leonardo; Cilli, Michele; Facchini, Andrea; Falasca, E; Malangone, W.; Panzani, I.; Degrassi, A.

doi:10.1038/sj.bmt.1704964

Cited by 27 publications

(21 citation statements)

References 33 publications

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“…Clinical trials have used cord blood-derived HSCs expanded through Notch ligands; 1 stromal coculture; 2 and automated, continuous perfusion culture systems, or "bioreactors." 3 Other approaches to expand HSCs include the use of aryl hydrocarbon receptor antagonists 4 and transduction of NF-Ya to activate HOXB4 using cell-penetrating peptides such as TAT. 5 Of these techniques, the highest expansion efficiencies have been obtained with Notch signaling, 1 which produced a 160-fold increase in CD34 ϩ cells compared with controls; however, long-term engraftment was not achieved.…”

Section: Introductionmentioning

confidence: 99%

SALL4 is a robust stimulator for the expansion of hematopoietic stem cells

Aguila

Liao

Yang³

et al. 2011

Blood

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HSCs are rare cells that have the unique ability to self-renew and differentiate into cells of all hematopoietic lineages. The lack of donors and current inability to rapidly and efficiently expand HSCs are roadblocks in the development of successful cell therapies. Thus, the challenge of ex vivo human HSC expansion remains a fertile and critically important area of investigation. Here, we show that either SALL4A-or SALL4B-transduced human HSCs obtained from the mobilized peripheral blood are capable of rapid and efficient expansion ex vivo by >10 000-fold for both CD34 ؉ /CD38 ؊ and CD34 ؉ / CD38 ؉ cells in the presence of appropriate cytokines. We found that these cells retained hematopoietic precursor cell immunophenotypes and morphology as well as normal in vitro or vivo potential for differentiation. The SALL4-mediated expansion was associated with enhanced stem cell engraftment and long-term repopulation capacity in vivo. Also, we demonstrated that constitutive expression of SALL4 inhibited granulocytic differentiation and permitted expansion of undifferentiated cells in 32D myeloid progenitors. Furthermore, a TAT-SALL4B fusion rapidly expanded CD34 ؉ cells, and it is thus feasible to translate this study into the clinical setting. Our findings provide a new avenue for investigating mechanisms of stem cell self-renewal and achieving clinically significant expansion of human HSCs. (Blood. 2011;118(3):576-585)

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Section: Introductionmentioning

confidence: 99%

SALL4 is a robust stimulator for the expansion of hematopoietic stem cells

Aguila

Liao

Yang³

et al. 2011

Blood

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“…This culture system has been used to expand fresh and cryopreserved human CD34 + -UCB cells for 12 days with an injection of fresh media on day 7 of culture. FACS analysis determined that most of the progenitors expanded were of myeloid and megakaryocytic lineage (Astori et al 2005). In a 38 mL culture of fresh CD34 + -UCB samples, 249.1 ± 49.5 and 33.0 ± 14.3-fold expansions of MNC and CD34 + cells were achieved, respectively.…”

Section: Stirred and Perfusion Systemsmentioning

confidence: 99%

Expansion of human hematopoietic stem cells for transplantation: trends and perspectives

2008

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Umbilical cord blood transplantation is clinically limited by its low progenitor cell content. Ex vivo expansion has become an alternative to increase the cell dose available for transplants. Expansion has been evaluated in several ways such as static cultures combining growth factors or mimicking the natural microenvironment using co-culture systems. However, static cultures have a small volume capacity and therefore large-scale expansion has been addressed using bioreactors. These and other biotechnological approaches for the expansion of hematopoietic progenitors and their utility to study several aspects of hematopoietic stem cell biology are discussed here.

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“…Astori et al (2005) reported that CD34 + cells were expanded by 12-fold (mean) in a commercial system. Yao et al (2006) showed an average 27-fold CD34 + cell expansion.…”

Section: ·00mentioning

confidence: 99%

Maternal plasma or human serum albumin in wash buffer enhances enrichment and ex vivo expansion of human umbilical cord blood CD34⁺ cells

et al. 2007

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SummaryUmbilical cord blood is a valuable source of haemopoietic stem/progenitor cells (HSC) for transplantation. This study explored the effect of maternal plasma/human serum albumin (HSA) in the purification and culture conditions of CD34+ cells derived from human umbilical cord blood. During CD34+ cell enrichment, including maternal plasma or HSA instead of fetal bovine serum (FBS) in the wash buffer, significantly increased the purity and the fold expansion of CD34+ cells. The increase in fold expansion of CD34+ cells was independent of CD34+ cell purity before expansion. With FBS, the mean fold expansion of CD34+ cells and total nucleated cells on day 7 was 9·7 ± 5·5 and 39·7 ± 13·7 respectively. The use of maternal plasma increased the mean fold expansion of CD34+ cells and total nucleated cells on day 7 to 28·2 ± 6·7 and 71·5 ± 15·4 respectively. When HSA was added to wash buffer, the mean fold expansion of CD34+ cells and total nucleated cells were 30·4 ± 10·5 and 83·5 ± 24·8 respectively. No statistical significance was found between using HSA and maternal plasma on total cell and CD34+ cell expansion. We propose that HSA in maternal plasma was responsible for the positive effect on CD34+ cell enrichment and expansion.

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Evaluation of ex vivo expansion and engraftment in NOD-SCID mice of umbilical cord blood CD34+ cells using the DIDECO ‘Pluricell System’

Cited by 27 publications

References 33 publications

SALL4 is a robust stimulator for the expansion of hematopoietic stem cells

SALL4 is a robust stimulator for the expansion of hematopoietic stem cells

Expansion of human hematopoietic stem cells for transplantation: trends and perspectives

Maternal plasma or human serum albumin in wash buffer enhances enrichment and ex vivo expansion of human umbilical cord blood CD34⁺ cells

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Evaluation of ex vivo expansion and engraftment in NOD-SCID mice of umbilical cord blood CD34+ cells using the DIDECO ‘Pluricell System’

Cited by 27 publications

References 33 publications

SALL4 is a robust stimulator for the expansion of hematopoietic stem cells

SALL4 is a robust stimulator for the expansion of hematopoietic stem cells

Expansion of human hematopoietic stem cells for transplantation: trends and perspectives

Maternal plasma or human serum albumin in wash buffer enhances enrichment and ex vivo expansion of human umbilical cord blood CD34+ cells

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About

Maternal plasma or human serum albumin in wash buffer enhances enrichment and ex vivo expansion of human umbilical cord blood CD34⁺ cells