On-Chip Neural Induction Boosts Neural Stem Cell Commitment: Toward a Pipeline for iPSC-Based Therapies

被引:0
|
作者
Jain, Saumey [1 ,2 ]
Voulgaris, Dimitrios [1 ,2 ,3 ]
Thongkorn, Surangrat [2 ,4 ]
Hesen, Rick [1 ]
Hagg, Alice [5 ]
Moslem, Mohsen [6 ]
Falk, Anna [5 ,6 ]
Herland, Anna [1 ,2 ,3 ,6 ]
机构
[1] KTH Royal Inst Technol, Div Micro & Nanosyst, Malvinas Vag 10, S-10044 Stockholm, Sweden
[2] KTH Royal Inst Technol, Div Nanobiotechnol, Sci Life Lab, Tomtebodavagen 23a, S-17165 Solna, Sweden
[3] Karolinska Inst, Ctr Integrated Med & Engn Sci, Dept Neurosci, AIMES, S-17165 Solna, Sweden
[4] Chulalongkorn Univ, Fac Allied Hlth Sci, Chulalongkorn Autism Res & Innovat Ctr Excellence, Dept Clin Chem, Bangkok 10330, Thailand
[5] Lund Univ, Lund Stem Cell Ctr, Dept Expt Med Sci, Neural Stem Cells, S-22184 Lund, Sweden
[6] Karolinska Inst, Dept Neurosci, S-17165 Solna, Sweden
基金
瑞典研究理事会;
关键词
differentiation; iPSC; microfluidic chip; microfluidics; neural stem cells; reprogramming; stem cell therapy; BIOPHYSICAL REGULATION; GENETIC-VARIATION; HUMAN ES; DIFFERENTIATION; CULTURE; MICROFLUIDICS; HETEROGENEITY; VARIABILITY; INHIBITION; DERIVATION;
D O I
10.1002/advs.202401859
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The clinical translation of induced pluripotent stem cells (iPSCs) holds great potential for personalized therapeutics. However, one of the main obstacles is that the current workflow to generate iPSCs is expensive, time-consuming, and requires standardization. A simplified and cost-effective microfluidic approach is presented for reprogramming fibroblasts into iPSCs and their subsequent differentiation into neural stem cells (NSCs). This method exploits microphysiological technology, providing a 100-fold reduction in reagents for reprogramming and a ninefold reduction in number of input cells. The iPSCs generated from microfluidic reprogramming of fibroblasts show upregulation of pluripotency markers and downregulation of fibroblast markers, on par with those reprogrammed in standard well-conditions. The NSCs differentiated in microfluidic chips show upregulation of neuroectodermal markers (ZIC1, PAX6, SOX1), highlighting their propensity for nervous system development. Cells obtained on conventional well plates and microfluidic chips are compared for reprogramming and neural induction by bulk RNA sequencing. Pathway enrichment analysis of NSCs from chip showed neural stem cell development enrichment and boosted commitment to neural stem cell lineage in initial phases of neural induction, attributed to a confined environment in a microfluidic chip. This method provides a cost-effective pipeline to reprogram and differentiate iPSCs for therapeutics compliant with current good manufacturing practices. This study highlights the development of a microfluidic platform to reprogram somatic cells from donors into induced pluripotent stem cells and further differentiate them into neural stem cells. This confined microfluidic platform boosts neural stem cell generation commitment at an early stage, as denoted by the pathway enrichment analysis. image
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页数:13
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