Abstract:
:Human induced pluripotent stem cells (hiPSCs) have generated a great deal of attention owing to their capacity for self-renewal and differentiation into the three germ layers of the body. Their discovery has facilitated a new era in biomedicine for understanding human development, drug screening, disease modeling, and cell therapy while reducing ethical issues and risks of immune rejection associated with traditional embryonic stem cells. Bioreactor-based processes have been the method of choice for the efficient expansion and differentiation of stem cells in controlled environments. Current protocols for the expansion of hiPSCs use horizontal impeller, paddle, or rocking wave mixing method bioreactors which require large static cell culture starting populations and achieve only moderate cell fold increases. This study focused on optimizing inoculation, agitation, oxygen, and nutrient availability for the culture of hiPSCs as aggregates in single-use, low-shear, vertical-wheel bioreactors. Under optimized conditions, we achieved an expansion of more than 30-fold in 6 days using a small starting population of cells and minimal media resources throughout. Importantly, we showed that that this optimized bioreactor expansion protocol could be replicated over four serial passages resulting in a cumulative cell expansion of 1.06E6-fold in 28 days. Cells from the final day of the serial passage were of high quality, maintaining a normal karyotype, pluripotent marker staining, and the ability to form teratomas in vivo. These findings demonstrate that a vertical-wheel bioreactor-based bioprocess can provide optimal conditions for efficient, rapid generation of high-quality hiPSCs to meet the demands for clinical manufacturing of therapeutic cell products.
journal_name
Stem Cells Transl Medjournal_title
Stem cells translational medicineauthors
Borys BS,So T,Colter J,Dang T,Roberts EL,Revay T,Larijani L,Krawetz R,Lewis I,Argiropoulos B,Rancourt DE,Jung S,Hashimura Y,Lee B,Kallos MSdoi
10.1002/sctm.19-0406subject
Has Abstractpub_date
2020-09-01 00:00:00pages
1036-1052issue
9eissn
2157-6564issn
2157-6580journal_volume
9pub_type
杂志文章abstract::Limbal stem cell (LSC) deficiency is a visually debilitating condition caused by abnormal maintenance of LSCs. It is treated by transplantation of donor-derived limbal epithelial cells (LECs), the success of which depends on the presence and quality of LSCs within the transplant. Understanding the immunobiological res...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0149
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journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2012-0155
更新日期:2013-08-01 00:00:00
abstract:UNLABELLED:Human cord blood (CB)-derived hematopoietic stem cells (HSCs) are an interesting source for HSC transplantation. However, the number of collected CB-HSCs is often too low for one transplantation; therefore, ex vivo expansion of CB-HSCs is desirable. Current expansion protocols are based on the use of cytokin...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0284
更新日期:2015-09-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.1002/sctm.20-0161
更新日期:2020-11-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) have immunomodulatory properties and support hematopoiesis in the bone marrow (BM). To develop a new strategy not only to prevent graft-vs-host disease (GVHD) but also enhance engraftment, a phase I trial of cord blood transplantation (CBT) combined with intra-BM injection of MSCs (MSC-CB...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
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abstract::Niemann-Pick disease, type C1 (NPC1) is a familial disorder that has devastating consequences on postnatal development with multisystem effects, including neurodegeneration. There is no Food and Drug Administration-approved treatment option for NPC1; however, several potentially therapeutic compounds have been identif...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0127
更新日期:2015-03-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0206
更新日期:2015-05-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.5966/sctm.2013-0184
更新日期:2014-05-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.18-0216
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0380
更新日期:2017-01-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 临床试验,杂志文章
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更新日期:2017-08-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.5966/sctm.2015-0152
更新日期:2016-03-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0086
更新日期:2018-02-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0121
更新日期:2014-12-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0279
更新日期:2016-05-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2016-0130
更新日期:2017-02-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
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journal_title:Stem cells translational medicine
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更新日期:2020-08-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章,多中心研究
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更新日期:2017-07-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.16-0160
更新日期:2017-04-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
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更新日期:2017-10-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2012-0022
更新日期:2012-11-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2012-0025
更新日期:2012-07-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
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更新日期:2019-10-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0078
更新日期:2017-08-01 00:00:00
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journal_title:Stem cells translational medicine
pub_type: 杂志文章,随机对照试验
doi:10.1002/sctm.18-0053
更新日期:2019-03-01 00:00:00