Surface-aminated electrospun nanofibers enhance adhesion and expansion of human umbilical cord blood hematopoietic stem/progenitor cells

Chua, Koon Jiew; Chai, Chee‐Yin; Lee, Peng-Chou; Tang, Yen-Ni; Ramakrishna, Seeram; Leong, Kam W.; Mao, Hai‐Quan

doi:10.1016/j.biomaterials.2006.06.017

Cited by 239 publications

(186 citation statements)

References 30 publications

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“…This unique adhesion pattern suggests that the submicron scale feature presented by electrospun fibers promotes contact guidance for dividing cells as they adhere and migrate away from the center of the colony. This observation is in contrast to HSPCs expanded on aminated two-dimensional film, which did not display significant adhesion and "colony formation" [11,12].Our data suggests that substrates that promoted cell adhesion also enhanced the preservation of CD34 + CD45 + phenotype and the primitive characteristics of cord blood CD34 + HSPCs. Cell adhesion/retention is known to be a crucial function of the stem cell niche in vivo.…”

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confidence: 53%

“…Suspension culture conditions differ drastically from conditions provided by the natural bone marrow microenvironment, where a complex network of stromal cells and extracellular matrix (ECM) serves as a stem cell niche that regulates HSPC functions such as homing, self-renewal, proliferation, and fate choice [2,8]. A growing body of evidence has suggested the importance of substrate surface chemistry and topography on the rate of HSPC proliferation and CD34 + cell expansion [9][10][11][12]. …”

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confidence: 99%

“…A growing body of evidence has suggested the importance of substrate surface chemistry and topography on the rate of HSPC proliferation and CD34 + cell expansion [9][10][11][12].…”

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confidence: 99%

“…We have noted previously that expanded cells adhered weakly to TCPS, unmodified, and PAAc-grafted surfaces. Most of expanded cells were washed off easily with very gentle rinsing [11,12]; only sparsely scattered cells remained adherent, as visualized by SEM imaging.Both EtDA and BuDA modified nanofiber meshes mediated significant adhesion. On day 3, small pockets of adherent HSPCs could be observed interacting with and proliferating on these fiber meshes ( Fig.…”

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confidence: 99%

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Functional nanofiber scaffolds with different spacers modulate adhesion and expansion of cryopreserved umbilical cord blood hematopoietic stem/progenitor cells

Chua

Chai

Lee

et al. 2007

Experimental Hematology

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Objective-Nanofiber scaffolds with amino groups conjugated to fiber surface through different spacers (ethylene, butylenes, and hexylene groups, respectively) were prepared and the effect of spacer length on adhesion and expansion of umbilical cord blood hematopoietic stem/progenitor cells (HSPCs) was investigated.Materials and Methods-Electrospun polymer nanofiber scaffolds were functionalized with poly (acrylic acid) grafting, followed by conjugation of amino groups with different spacers. HSPCs were expanded on aminated scaffolds for 10 days. Cell proliferation, surface marker expression, clonogenic potential, and nonobese diabetic (NOD)/severe combined immunodeficient (SCID) repopulation potential of the expanded cells were evaluated following expansion culture.Results-Aminated nanofiber scaffolds with ethylene and butylene spacers showed high-expansion efficiencies (773-and 805-fold expansion of total cells, 200-and 235-fold expansion of CD34 + CD45 + cells, respectively). HSPC proliferation on aminated scaffold with hexylene spacer was significantly lower (210-fold expansion of total cells and 86-fold expansion of CD34 + CD45 + cells), but maintained the highest CD34 + CD45 + cell fraction (41.1%). Colony-forming unit granulocyte-erythrocyte-monocyte-megakaryocyte and long-term culture-initiating cell maintenance was similar for HSPCs expanded on all three aminated nanofiber scaffolds; nevertheless, the NOD/SCID mice engraftment potential of HSPCs expanded on aminoethyl and aminobutyl conjugated nanofibers was significantly higher than that on aminohexyl conjugated nanofibers.Conclusion-This study demonstrated that aminated nanofibers are superior substrates for ex vivo HSPC expansion, which was correlated with the enhanced HSPC adhesion to these aminated nanofibers. The spacer, through which amino groups were conjugated to nanofiber surface, affected the expansion outcome. Our results highlighted the importance of scaffold topography and cellsubstrate interaction to regulating HSPC proliferation and self-renewal in cytokine-supplemented expansion.Offprint requests to: Hai-Quan Mao, Ph.D., Department of Materials Science and Engineering, Johns Hopkins University, 102 Maryland Hall, 3400 N. Charles Street, Baltimore, MD 21218; E-mail: hmao@jhu.edu. In conventional ex vivo expansion culture, HSPCs are generally regarded as suspension cells and numerous protocols implement HSPC suspension cultures in flasks or bags in the presence of various combinations of early acting cytokines [3][4][5][6][7]. The importance of topographical and substrate-immobilized biochemical cues has not been taken into consideration in these culture systems. Suspension culture conditions differ drastically from conditions provided by the natural bone marrow microenvironment, where a complex network of stromal cells and extracellular matrix (ECM) serves as a stem cell niche that regulates HSPC functions such as homing, self-renewal, proliferation, and fate choice [2,8]. A growing body of evidence has suggested the importance of...

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mentioning

confidence: 53%

mentioning

confidence: 99%

“…A growing body of evidence has suggested the importance of substrate surface chemistry and topography on the rate of HSPC proliferation and CD34 + cell expansion [9][10][11][12].…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Functional nanofiber scaffolds with different spacers modulate adhesion and expansion of cryopreserved umbilical cord blood hematopoietic stem/progenitor cells

Chua

Chai

Lee

et al. 2007

Experimental Hematology

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114

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“…Moreover, further advances in polymer chemistry resulted in the development of novel nanomaterials with unique spatial orientation of molecular groups, including dendrimers [150], star-polymers [151], and cross-linked polymer micelles [152][153][154][155]. In parallel, advances in nanomanufacturing and nanofabrication led to the development of carbon nanotubes [156,157], and polymeric nanofibers [158,159]. In terms of delivery of bioactive molecules, these materials are at relatively early development stages.…”

Section: Nanocarriers For Cns Drug Deliverymentioning

confidence: 99%

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders

Kabanov

Gendelman

2007

Progress in Polymer Science

242

138

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Neurodegenerative and infectious disorders including Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and stroke are rapidly increasing as population's age. Alzheimer's disease alone currently affects 4.5 million Americans, and more than $100 billion is spent per year on medical and institutional care for affected people. Such numbers will double in the ensuing decades. Currently disease diagnosis for all disorders is made, in large measure, on clinical grounds as laboratory and neuroimaging tests confirm what is seen by more routine examination. Achieving early diagnosis would enable improved disease outcomes. Drugs, vaccines or regenerative proteins present "real" possibilities for positively affecting disease outcomes, but are limited in that their entry into the brain is commonly restricted across the blood-brain barrier. This review highlights how these obstacles can be overcome by polymer science and nanotechnology. Such approaches may improve diagnostic and therapeutic outcomes. New developments in polymer science coupled with cell-based delivery strategies support the notion that diseases that now have limited therapeutic options can show improved outcomes by advances in nanomedicine.

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2007

Science and Technology of Polymer Nanofibers

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Surface-aminated electrospun nanofibers enhance adhesion and expansion of human umbilical cord blood hematopoietic stem/progenitor cells

Cited by 239 publications

References 30 publications

Functional nanofiber scaffolds with different spacers modulate adhesion and expansion of cryopreserved umbilical cord blood hematopoietic stem/progenitor cells

Functional nanofiber scaffolds with different spacers modulate adhesion and expansion of cryopreserved umbilical cord blood hematopoietic stem/progenitor cells

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders

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