Proteomics and Microvascular Chip Identify Blood Biomarker Candidates in Calciphylaxis Stem Cell Therapy. Hu et al.

Description

This de-identified dataset encompasses clinical, laboratory, and proteomic data from patients with calciphylaxis, a rare and high-mortality condition also known as calcific uremic arteriolopathy (CUA), who were treated with human amnion-derived mesenchymal stem cells (hAMSCs). This disorder predominantly arises in the context of chronic kidney disease. The dataset further includes information from uremic control subjects, comprising demographics, comorbidities, dialysis history, and medication records across discovery (3 CUA cases and 10 uremic controls) and independent validation (8 CUA cases and 20 uremic controls) cohorts. The data comprise: 1. Proteomics: Static and dynamic proteomic profiles from the discovery cohort, deposited in iProX, identified Thrombospondin-1 (THBS1) as a leading upregulated hub associated with coagulation and wound healing. In vitro proteomic analyses further demonstrated that blockade of the THBS1/TGF-β1 axis attenuates endothelial dysfunction induced by CUA serum (data deposited in iProX). 2. Potential Biomarker Validation (ELISA): Quantitative validation of elevated plasma THBS1 and TGF-β1 levels was conducted using ELISA in both discovery and validation cohorts, confirming a significant reduction three days post-hAMSC therapy. However, in Patient 1 from the discovery cohort, plasma THBS1 and TGF-β1 levels remained low throughout the 15-month follow-up period but increased as the frequency of hAMSC treatment decreased. 3. Microvascular Chip Analysis: Quantitative assessment of integrated density and cell viability using a human microvascular chip to analyze calciphylaxis-associated vascular injury and evaluate the therapeutic effects of hAMSCs in vitro. 4. Clinical Outcomes: Longitudinal evaluations of wound healing utilizing the Bates-Jensen Wound Assessment Tool for CUA (BWAT-CUA), pain measured by the Visual Analog Scale (VAS), and systemic inflammation assessed via high-sensitivity C-reactive protein (hs-CRP). These integrated findings implicate THBS1 as a potential biomarker and therapeutic target, supporting hAMSCs as a mechanism-based treatment for calciphylaxis. All data are anonymized to ensure patient privacy.

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Funders

• Key Projects of Medical Scientific Research Funded by the Health Commission of Jiangsu Province

  Grant ID: K2024005
• the National Natural Science Foundation of China

  Grant ID: 81270408
• the National Natural Science Foundation of China

  Grant ID: 81570666
• National Key R&D Program of China

  Grant ID: 2022YF0608403
• National Key R&D Program of China

  Grant ID: 2021YFA1301600
• Natural Science Foundation of Jiangsu Province

  Grant ID: BK20243054
• Outstanding Young and Middle-Aged Talents Support Program of The First Affiliated Hospital with Nanjing Medical University

  Grant ID: Jiangsu Province Hospital
• Clinical Capacity Enhancement Project

  Grant ID: JSPH-MA-2023-7
• the National Key Research and Development Program of China

  Grant ID: 2017YFC1001303
• the State Key Laboratory of Reproductive Medicine and Offspring Health Program

  Grant ID: SKLRM-K202105
• Specialized Diseases Clinical Research Fund of Jiangsu Province Hospital

  Grant ID: XB202403
• Jiangsu Province Hospital Maternal and Child Health High-Quality Development Research Program

  Grant ID: GZL2504
• "Pioneer" and "Leading Goose" R&D Program of Zhejiang

  Grant ID: 2024SSYS0035
• Westlake Omics Junior Clinician Support Program 2021, and Jiangsu Provincial Graduate Research and Practice Innovation Program

  Grant ID: SJCX25_0797

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