Stem Cells International / 2019 / Article / Tab 1

Review Article

The Application of Induced Pluripotent Stem Cells in Pathogenesis Study and Gene Therapy for Vascular Disorders: Current Progress and Future Challenges

Table 1

List of studies using human IPSCs derived from patients for pathogenesis investigation.

Vascular disordersGeneChr, exon, mutationPathogenesis-related SMC/EC phenotype and signal changesiPSC resourcePluripotency markers (+)Gene therapy, effectAuthor, yearReference

Marfan syndrome (MFS)FBN115, 30, C1242YMFSC1242Y-iPSC-NC-SMC: proliferative capacity↓, cell death↑, contractility↓, propagating calcium↓, MMP9 expression in stretching↑; MFSC1242Y-ECM: fibrillin-1 deposition↓, TGF-β signaling↑, collagen I deposition and stiffness↑Patient dermal fibroblastsOCT3/4, SOX2, SSEA4, TRA-1-60CRISPR/Cas9 gene editing, rescues fibrillin-1 phenotypeGranata et al., 2016[15]
Loeys-Dietz syndrome (LDS)TGFBR23, 4, R193WNot detectedPatient peripheral blood mononuclear cellsOCT4, SOX2, NANOG, TRA-1-60Not referredHu et al., 2017[18]
Williams-Beuren syndrome (WBS)ELN7, not referred, 7q11.23 heterozygous deletionWBS7q11.23deletion-iPSC-SMC: immature phenotype↑, proliferation↑, expression of differentiated SMC markers↓, response to vasoactive agonists↓, vascular tuber formation↓, calcium flux↓Patient skin fibroblastsNANOG, OCT4, SSEA4EBPL2 peptide injection, partially rescues WBS cell phenotypeKinnear et al., 2013[19]
Hutchinson-Gilford progeria syndrome (HGPS)LMNA1, 11, G608RHGPSG608R-iPSC-SMC: senescence under hypoxia↑, nuclear dysmorphology↑, DNA damage↑, cell viability↓Patient skin fibroblastsOCT4, NANOG, SOX2, SSEA4, TRA-1-80Reprogramming, low expression of LMNAZhang et al., 2011[20]
Pulmonary artery hypertension (PAH)BMPR22, 3, C118WPAHC118W-iPSC-EC: capability of adhesion, survival, migration, and angiogenesis↓, BMPR2 signaling↓Patient skin fibroblastsOCT4, KLF4, NANOG, SOX2, TRA-1-81, SSEA4CRISPR/Cas9 gene editing, rescues PAH cell phenotypeGu et al., 2017[21]
Bicuspid aortic valve- (BAV-) related thoracic aortic aneurysm (TAA)No mutation of NOTCH1 was found.Not referredBAV/TAA-iPSC-SMC: differentiation↓, contraction↓, TGF-β signaling↓, mTOR signaling↑Patient peripheral blood mononuclear cellsOCT4, SOX2, NANOG, SSEA4, TRA-1-60, TRA-1-81mTOR inhibitor rapamycin, rescues cell phenotypeJiao et al., 2016[22]
Supravalvular aortic stenosis (SVAS) syndromeELN7, 9, 4 bp insert mutationSVASinsert-iPSC-SMC: property of contractile SMC↓, proliferation↑, migration↑, ERK1/2 activation↑Patient epicardial coronary artery VSMCsTRA-1-60, SSEA4, NANOG, OCT4Elastin, rescues SVAS-SMC phenotypeGe et al., 2012[23]
Huntington’s disease (HD)HTT4, not referred, 66 CAG repeatsHDrepeats-iPSC-BMECs: angiogenic potential↑, migration↑, permeability↑, barrier property↓, endothelial transcytosis↓Patient skin fibroblastsOCT4, SOX2, KLF4, L-MYCWnt inhibitor rescues angiogenesis defectsLim et al., 2017[24]