Abstract:
:Patient-specific induced pluripotent stem cells (iPSCs) hold great promise for many applications, including disease modeling to elucidate mechanisms involved in disease pathogenesis, drug screening, and ultimately regenerative medicine therapies. A frequently used starting source of cells for reprogramming has been dermal fibroblasts isolated from skin biopsies. However, numerous repositories containing lymphoblastoid cell lines (LCLs) generated from a wide array of patients also exist in abundance. To date, this rich bioresource has been severely underused for iPSC generation. We first attempted to create iPSCs from LCLs using two existing methods but were unsuccessful. Here we report a new and more reliable method for LCL reprogramming using episomal plasmids expressing pluripotency factors and p53 shRNA in combination with small molecules. The LCL-derived iPSCs (LCL-iPSCs) exhibited identical characteristics to fibroblast-derived iPSCs (fib-iPSCs), wherein they retained their genotype, exhibited a normal pluripotency profile, and readily differentiated into all three germ-layer cell types. As expected, they also maintained rearrangement of the heavy chain immunoglobulin locus. Importantly, we also show efficient iPSC generation from LCLs of patients with spinal muscular atrophy and inflammatory bowel disease. These LCL-iPSCs retained the disease mutation and could differentiate into neurons, spinal motor neurons, and intestinal organoids, all of which were virtually indistinguishable from differentiated cells derived from fib-iPSCs. This method for reliably deriving iPSCs from patient LCLs paves the way for using invaluable worldwide LCL repositories to generate new human iPSC lines, thus providing an enormous bioresource for disease modeling, drug discovery, and regenerative medicine applications.
journal_name
Stem Cells Transl Medjournal_title
Stem cells translational medicineauthors
Barrett R,Ornelas L,Yeager N,Mandefro B,Sahabian A,Lenaeus L,Targan SR,Svendsen CN,Sareen Ddoi
10.5966/sctm.2014-0121subject
Has Abstractpub_date
2014-12-01 00:00:00pages
1429-34issue
12eissn
2157-6564issn
2157-6580pii
sctm.2014-0121journal_volume
3pub_type
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journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
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pub_type: 杂志文章
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journal_title:Stem cells translational medicine
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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
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pub_type: 杂志文章,评审
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journal_title:Stem cells translational medicine
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journal_title:Stem cells translational medicine
pub_type: 临床试验,杂志文章
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journal_title:Stem cells translational medicine
pub_type: 杂志文章
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pub_type: 杂志文章
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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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pub_type: 杂志文章,评审
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