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Title 

Biomarker discovery by modeling behcet's disease with patient-specific human induced pluripotent stem cells

Authors 

Mi Young SonYoung-Dae KimBinna SeolMi Ok LeeHee Jun NaB YooJ S ChangYee Sook Cho

Publisher 

Mary Ann Liebert

Issue Date 

2017

Citation 

Stem Cells and Development

Keywords 

Behcets diseasebiomarkerCXCL1drug discoveryhematopoietic precursor cellsinduced pluripotent stem cells

Abstract 

Beh?et's disease (BD) is a chronic inflammatory and multisystemic autoimmune disease of unknown etiology. Due to the lack of a specific test for BD, its diagnosis is very difficult and therapeutic options are limited. Induced pluripotent stem cell (iPSC) technology, which provides inaccessible disease-relevant cell types, opens a new era for disease treatment. In this study, we generated BD iPSCs from patient somatic cells and differentiated them into hematopoietic precursor cells (BD iPSC-HPCs) as BD model cells. Based on comparative transcriptome analysis using our BD model cells, we identified eight novel BD-specific genes, AGTR2, CA9, CD44, CXCL1, HTN3, IL-2, PTGER4, and TSLP, which were differentially expressed in BD patients compared with healthy controls or patients with other immune diseases. The use of CXCL1 as a BD biomarker was further validated at the protein level using both a BD iPSC-HPC-based assay system and BD patient serum samples. Furthermore, we show that our BD iPSC-HPC-based drug screening system is highly effective for testing CXCL1 BD biomarkers, as determined by monitoring the efficacy of existing anti-inflammatory drugs. Our results shed new light on the usefulness of patient-specific iPSC technology in the development of a benchmarking platform for disease-specific biomarkers, phenotype- or target-driven drug discovery, and patient-tailored therapies.

ISSN 

1525-8165

Link 

http://dx.doi.org/10.1089/scd.2016.0181

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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