<i>Ex vivo</i> amplification of human hematopoietic stem and progenitor cells in an alginate three‐dimensional culture system

Yuan, Yan; Tse, Kai-Tai; Sin, Fion Wan-Yee; Xue, Bofu; Fan, Huimin; Xie, Yanhui

doi:10.1111/j.1751-553x.2011.01324.x

Cited by 15 publications

(12 citation statements)

References 25 publications

(40 reference statements)

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“…Similar data regarding the change in BFU-E levels have also been reported in the collagen bead 3D culture system [21]. One explanation for the lower BFU-E number is that in both 3D culture systems the cytokine EPO was absent [27].…”

Section: Discussionsupporting

confidence: 77%

3-Dimensional nano-fibre scaffold forex vivoexpansion of cord blood haematopoietic stem cells

Mousavi

Abroun

Soleimani

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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Cord blood (CB) haematopoietic stem cell (HSC) is an alternative source of HSC transplantation. The limited cell number greatly restricts their clinic-scale therapeutic applications. The objective of this study was an ex vivo expansion of CB HSCs in a new three-dimensional polycaprolactone nano-scaffold coated with fibronectin (FN). First, we isolated CB CD34+ cells and cultured 10 days in presence of growth factors. The evaluation was performed by qRT-PCR, flow cytometry and clonogenicity. 3D PCL nano-scaffold coated with FN produced significantly higher total nucleated cells and CD34+ cells (p < .05) and also had significantly higher homing and self-renewality genes than 2D cell culture and before expansion (p < .05). The expression of CXCR-4, VLA-4, VLA-5 and LFA-1, and also HOXB-4, HOXA-9, BMI-1 and hTERT genes was higher in 3D than 2D. The CD13, CD14, CD33, CD34 and CD45 markers were significantly higher and CD2, CD3 and CD19 markers were significantly lower in 3D scaffold than 2D cell culture (p < .05). The type and number of colonies in 2D culture were lower than 3D culture medium (p > .05). 3D PCL nano-scaffold coated with FN could better keep specifications homing and self renewality of CB HSCs after expansion.

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Section: Discussionsupporting

confidence: 77%

3-Dimensional nano-fibre scaffold forex vivoexpansion of cord blood haematopoietic stem cells

Mousavi

Abroun

Soleimani

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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“…Furthermore, encapsulation ensures HSC interaction with biomolecules covalently tethered to the hydrogel matrix, which can help control HSC behavior. Several groups have investigated the use of 3D scaffolds for ex vivo HSPC expansion (Bagley et al, ; Braccini et al, ; Feng et al, ; Ferreira et al, ; Lee and Kotov, ; Leisten et al, ; Levee et al, ; Li et al, ; Raic et al, ; Yuan et al, ). Some of this work is not truly 3D culture but the culture of HSPCs on the surfaces of porous 3D substrates (Feng et al, ; Lee and Kotov, ).…”

Section: Discussionmentioning

confidence: 99%

“…Levee et al () encapsulated whole bone marrow within an alginate‐poly‐L‐lysine copolymer and observed total cell growth after 16–19 days in culture, though most of the cells were more differentiated hematopoietic progenitors. Yuan et al () demonstrated the ability to encapsulate cord blood HSPCs within alginate scaffolds; their results showed an improvement in HSPC expansion after 12 days in 3D scaffolds compared to conventional 2D cell culture. Raic et al () cocultured HSPCs and MSCs within microporous PEG hydrogels functionalized with RGDS and observed improved HSPC expansion compared to 2D coculture over 4 days.…”

Section: Discussionmentioning

confidence: 99%

Bioactive poly(ethylene glycol) hydrogels to recapitulate the HSC niche and facilitate HSC expansion in culture

Cuchiara

Coşkun

Banda

et al. 2015

Biotech & Bioengineering

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Hematopoietic stem cells (HSCs) have been used therapeutically for decades, yet their widespread clinical use is hampered by the inability to expand HSCs successfully in vitro. In culture, HSCs rapidly differentiate and lose their ability to self-renew. We hypothesize that by mimicking aspects of the bone marrow microenvironment in vitro we can better control the expansion and differentiation of these cells. In this work, derivatives of poly(ethylene glycol) diacrylate hydrogels were used as a culture substrate for hematopoietic stem and progenitor cell (HSPC) populations. Key HSC cytokines, stem cell factor (SCF) and interferon-γ (IFNγ), as well as the cell adhesion ligands RGDS and connecting segment 1 were covalently immobilized onto the surface of the hydrogels. With the use of SCF and IFNγ, we observed significant expansion of HSPCs, ∼97 and ∼104 fold respectively, while maintaining c-kit(+) lin(-) and c-kit(+) Sca1(+) lin(-) (KSL) populations and the ability to form multilineage colonies after 14 days. HSPCs were also encapsulated within degradable poly(ethylene glycol) hydrogels for three-dimensional culture. After expansion in hydrogels, ∼60% of cells were c-kit(+), demonstrating no loss in the proportion of these cells over the 14 day culture period, and ∼50% of colonies formed were multilineage, indicating that the cells retained their differentiation potential. The ability to tailor and use this system to support HSC growth could have implications on the future use of HSCs and other blood cell types in a clinical setting.

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“…The small number of hematopoietic stem/progenitor cells in UCBs limits their widespread use for transplantation and gene therapy [29, 30]. Thus, efficient and continuous ex vivo expansion of purified hematopoietic stem/progenitors without loss of repopulation capacity has become a priority to meet the clinical requirements for allogeneic transplantation [31]. In this respect, our data suggest that expansion of hematopoietic progenitors with multi-lineage potential of UCBs by E2 signaling enables UCBs to become a prioritized source for future clinical applications.…”

Section: Discussionmentioning

confidence: 99%

Improved hematopoietic differentiation of human pluripotent stem cells via estrogen receptor signaling pathway

et al. 2016

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BackgroundAside from its importance in reproduction, estrogen (E2) is known to regulate the proliferation and differentiation of hematopoietic stem cells in rodents. However, the regulatory role of E2 in human hematopoietic system has not been investigated. The purpose of this study is to investigate the effect of E2 on hematopoietic differentiation using human pluripotent stem cells (hPSCs).ResultsE2 improved hematopoietic differentiation of hPSCs via estrogen receptor alpha (ER-α)-dependent pathway. During hematopoietic differentiation of hPSCs, ER-α is persistently maintained and hematopoietic phenotypes (CD34 and CD45) were exclusively detected in ER-α positive cells. Interestingly, continuous E2 signaling is required to promote hematopoietic output from hPSCs. Supplementation of E2 or an ER-α selective agonist significantly increased the number of hemangioblasts and hematopoietic progenitors, and subsequent erythropoiesis, whereas ER-β selective agonist did not. Furthermore, ICI 182,780 (ER antagonist) completely abrogated the E2-induced hematopoietic augmentation. Not only from hPSCs but also from human umbilical cord bloods, does E2 signaling potentiate hematopoietic development, suggesting universal function of E2 on hematopoiesis.ConclusionsOur study identifies E2 as positive regulator of human hematopoiesis and suggests that endocrine factors such as E2 influence the behavior of hematopoietic stem cells in various physiological conditions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13578-016-0111-9) contains supplementary material, which is available to authorized users.

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Ex vivo amplification of human hematopoietic stem and progenitor cells in an alginate three‐dimensional culture system

Abstract: This study demonstrates a new and efficient method to amplify the CD34+ human cord blood hematopoietic stem/progenitor cells in a 3D alginate culture system ex vivo for extended periods while retaining the hematopoietic reconstruction capacity.

Cited by 15 publications

References 25 publications

3-Dimensional nano-fibre scaffold forex vivoexpansion of cord blood haematopoietic stem cells

3-Dimensional nano-fibre scaffold forex vivoexpansion of cord blood haematopoietic stem cells

Bioactive poly(ethylene glycol) hydrogels to recapitulate the HSC niche and facilitate HSC expansion in culture

Improved hematopoietic differentiation of human pluripotent stem cells via estrogen receptor signaling pathway

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