Epigenetic reprogramming induces the expansion of cord blood stem cells

Chaurasia, Pratima; Gajzer, David; Schaniel, Christoph; D’Souza, Sunita L.; Hoffman, Ronald

doi:10.1172/jci70313

Cited by 140 publications

(156 citation statements)

References 64 publications

(137 reference statements)

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“…However, when patients were transplanted with HSPC that had been cocultured in the presence of supportive stromal layers, the time to neutrophil and platelet reconstitution was significantly shortened 38. Other approaches to expand the numbers of transplantable HSPC within a unit of CB have included or involved activation of endogenous Notch receptors 39, nicotinamide analogs 40, aryl hydrocarbon receptor antagonists 41, copper chelators 1, histone deacetylase inhibitors 42, and engraftment enhancers such as PEG2 43 and CXCR4 44. These newer approaches have all shown great potential for the ex vivo expansion of CB‐HSPC or accelerating their engraftment.…”

Section: Discussionmentioning

confidence: 99%

Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with Functionally Integrated Three-Dimensional Microenvironments

Mokhtari

Baptista

Vyas

et al. 2018

Stem Cells Translational Medicine

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Despite advances in ex vivo expansion of cord blood‐derived hematopoietic stem/progenitor cells (CB‐HSPC), challenges still remain regarding the ability to obtain, from a single unit, sufficient numbers of cells to treat an adolescent or adult patient. We and others have shown that CB‐HSPC can be expanded ex vivo in two‐dimensional (2D) cultures, but the absolute percentage of the more primitive stem cells decreases with time. During development, the fetal liver is the main site of HSPC expansion. Therefore, here we investigated, in vitro, the outcome of interactions of primitive HSPC with surrogate fetal liver environments. We compared bioengineered liver constructs made from a natural three‐dimensional‐liver‐extracellular‐matrix (3D‐ECM) seeded with hepatoblasts, fetal liver‐derived (LvSt), or bone marrow‐derived stromal cells, to their respective 2D culture counterparts. We showed that the inclusion of cellular components within the 3D‐ECM scaffolds was necessary for maintenance of HSPC viability in culture, and that irrespective of the microenvironment used, the 3D‐ECM structures led to the maintenance of a more primitive subpopulation of HSPC, as determined by flow cytometry and colony forming assays. In addition, we showed that the timing and extent of expansion depends upon the biological component used, with LvSt providing the optimal balance between preservation of primitive CB HSPC and cellular differentiation. Stem Cells Translational Medicine 2018;7:271–282

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Section: Discussionmentioning

confidence: 99%

Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with Functionally Integrated Three-Dimensional Microenvironments

Mokhtari

Baptista

Vyas

et al. 2018

Stem Cells Translational Medicine

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“…The supplementation of human cord blood CD34 + cells in culture with the HDAC inhibitor valproic acid for 7 d upregulated expression of stemness genes, elevated aldehyde dehydrogenase activity, and stimulated a 36-fold increase of SCIDrepopulating cells [180]. Another HDAC inhibitor chlamydocin also induced expansion of HSCs in culture [181].…”

Section: Epigenetic Modifiersmentioning

confidence: 99%

Ex vivo expansion of hematopoietic stem cells

Xie

Zhang

2015

Sci. China Life Sci.

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Ex vivo expansion of hematopoietic stem cells (HSCs) would benefit clinical applications in several aspects, to improve patient survival, utilize cord blood stem cells for adult applications, and selectively propagate stem cell populations after genetic manipulation. In this review we summarize and discuss recent advances in the culture systems of mouse and human HSCs, which include stroma/HSC co-culture, continuous perfusion and fed-batch cultures, and those supplemented with extrinsic ligands, membrane transportable transcription factors, complement components, protein modification enzymes, metabolites, or small molecule chemicals. Some of the expansion systems have been tested in clinical trials. The optimal condition for ex vivo expansion of the primitive and functional human HSCs is still under development. An improved understanding of the mechanisms for HSC cell fate determination and the HSC culture characteristics will guide development of new strategies to overcome difficulties. In the future, development of a combination treatment regimen with agents that enhance self-renewal, block differentiation, and improve homing will be critical. Methods to enhance yields and lower cost during collection and processing should be employed. The employment of an efficient system for ex vivo expansion of HSCs will facilitate the further development of novel strategies for cell and gene therapies including genome editing. ex vivo expansion, hematopoietic stem cells, niche, signal transduction, cord blood, transplantation, SCID-repopulating cell, genome editing, CRISPR/Cas9 Citation:Xie JJ, Zhang CC. Ex vivo expansion of hematopoietic stem cells.

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“…Additional factors or small molecules that enhance UCB HSPC proliferation or function include the Notch Delta-like ligand 1 (DLL1), StemRegenin1 (SR 1), the copper chelator tetraethylenepentamide (TEPA), GSK3 inhibitors of WNT signaling, p18 a speciic inhibitor of cyclin-dependent kinase (CDK), pyrimidoindole derivatives such as UM1 1, speciic miRNAs, and epigenetic modiiers such as histone deacetylase (HDAC) inhibitors and nicotinamide, as well as additional growth factors such as the designer cytokine hyper-IL-6, oncostatin M, IL-11, angiopoietin-like 5, and other angiopoietin-like molecules and IGFBP2 [120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139]. Coculture of UCB cells with mesenchymal stromal cells has also been examined [140].…”

Section: Further Cytokine and Small Molecule Addition To Expand Umentioning

confidence: 99%

“…Class I comprises HDAC1-3 and HDAC8, class II consists of HDAC4-and HDAC9-10, class III are the sirtuins SIRT1-that require NAD as a cosubstrate for their activity, and class IV comprises HDAC11 [149]. [121]. To evaluate the repopulating activity of expanded cells, sublethally irradiated NSG mice were injected with cells expanded in cytokines (SCF, IL-3, FtL-3, and TPO) and HDAC inhibitors for days.…”

Section: Further Cytokine and Small Molecule Addition To Expand Umentioning

confidence: 99%

Umbilical Cord Blood Hematopoietic Stem and Progenitor Cell Expansion for Therapeutic Use

Watt¹,

Hua²

2017

Umbilical Cord Blood Banking for Clinical Application and Regenerative Medicine

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Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for severe hematological malignancies and other severe disorders of the blood, immune system, and bone marrow. It is the most successful regenerative therapy to date, with 2013 marking the one millionth HSCT and the 25th anniversary of the irst umbilical cord blood (UCB) HSCT. UCB has most often been used for allogeneic HSCT when a matched bone marrow or peripheral blood donor is unavailable. Recently, novel genome editing technologies to correct inherited gene disorders or to modulate biomarkers/ receptors on HSC and the potential use of HSCT for a variety of other nonmalignant conditions have led to a surge of interest in autologous HSCT, with the HSC source depending on the condition to be treated. UCB HSCs may be used to generate red blood cells, granulocytes, or platelets ex vivo for transfusion into diicult-to-transfuse patients. Alternatively, UCB may be reprogrammed to induced pluripotent stem cells or used to generate cell lines, which can then be diferentiated into diferent cell lineages for transfusion or used as diagnostic reagents. Disadvantages of UCB are its restricted cell numbers and delayed hematological engraftment. Here, UCB HSC expansion/ manipulation ex vivo and clinical applications are addressed.

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Epigenetic reprogramming induces the expansion of cord blood stem cells

Cited by 140 publications

References 64 publications

Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with Functionally Integrated Three-Dimensional Microenvironments

Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with Functionally Integrated Three-Dimensional Microenvironments

Ex vivo expansion of hematopoietic stem cells

Umbilical Cord Blood Hematopoietic Stem and Progenitor Cell Expansion for Therapeutic Use

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