Multi-omics Analysis Reveals Prognostic Biomarker Candidates for Calcific Uremic Arteriolopathy Patients Treated with Stem Cells
Ye, X.; Lu, S.; Qin, L.; Sun, Y.; Zhang, J.; Zeng, M.; Wu, J.; Hu, J.; Chen, F.; Liu, K.; Yuan, Y.; Ouyang, C.; Cui, H.; Li, L.; Zhang, L.; Yu, Y.; Ge, W.; Ren, H.; Zhang, L.; Zhu, J.; Yu, Y.; Li, C.; Su, Z.; Luo, D.; Tang, S.; Tang, X.; Liao, M.; Fang, G.; Bian, A.; Li, F.; Mao, X.; Cui, Y.; Jiang, C.; Ma, X.; Ning, S.; Gao, Z.; Zhao, B.; Wu, D.; Liu, C.; Wang, X.; Liang, N.; Xing, C.; Liu, J.; Guo, T.; Zhu, Y.; Wang, N.
Show abstract
Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is an orphan disease without proven therapies, we rescued it with human amnion-derived mesenchymal stem cells (hAMSCs). In a discovery cohort of 10 uremic patients and 3 CUA patients, plasma proteomic analysis showed core differentially expressed proteins (DEPs) Thrombospondin 1 (THBS1) and Latent transforming growth factor (TGF)-{beta} binding protein 1 (LTBP1) decreased significantly after 3 days of hAMSC treatment. Single-cell transcriptome sequencing of peripheral blood mononuclear cells (PBMCs) indicated megakaryocytes were the source of THBS1 in CUA patient. Same as the discovery cohort, plasma THBS1 and TGF-{beta}1 levels were increased in seven CUA patients compared to the uremic group (n=20), as measured by enzyme-linked immunosorbent assay (ELISA) in the validation cohort. They can be inhibited after hAMSC treatment and increased as the frequency of therapy decreased. THBS1 and its receptor, CD47, were increased in the CUA skin. THBS1 and TGF-{beta}1 are biomarker candidates for calciphylaxis.
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