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May 5, 2023Basic Research in CardiologyOpen Access

Multilineage contribution of CD34+ cells in cardiac remodeling after ischemia/reperfusion injury

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Key result

Depletion of Cd34+ cells alleviated the severity of ventricular fibrosis and improved cardiac function after ischemia/reperfusion injury.

Why the study?

Ambiguous results from multiple CD34+ cell-based therapeutic trials in heart disease have halted large-scale stem/progenitor cell application, leaving the biological functions of heterogeneous CD34+ cell populations and their net effect on cardiac remodeling unclear.

Population

Human and mouse ischemic hearts, including an inducible Cd34 lineage-tracing mouse model

Comparison

Depletion of Cd34+ cells vs non-depletion after ischemia/reperfusion injury

Design

Preclinical animal and translational human tissue study using single-cell RNA sequencing and lineage tracing

Authors

JXJun XieLJLiujun JiangJWJunzhuo Wang

Discussion

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Overview

Cd34+ depletion attenuates post-I/R fibrosis in animals; hypothesis-generating for human remodeling therapies, should not yet change practice.

Structured PICO

P
Population
Mouse models of ischemia/reperfusion injury and human infarcted heart samples were analyzed to determine the role of CD34+ cells in cardiac remodeling.
I
Intervention
Lineage tracing and genetic depletion of Cd34+ cells using tamoxifen-inducible Cre-loxP mouse models.
C
Comparator
Wild-type mice or sham-operated mice.
O
Outcome
Cellular contribution to cardiac remodeling, ventricular fibrosis, and cardiac function (LVEF, LVEDD, LVESD) evaluated by single-cell RNA sequencing, echocardiography, and histology.surrogate

Heterogeneous CD34+ cell populations actively participate in post-infarction cardiac remodeling by differentiating into profibrotic mesenchymal cells, angiogenic endothelial cells, and pro-inflammatory macrophages.

Limitations

  • Discrepancies of Cre expression in different cell types
  • Diverse efficiency of DT-induced cell ablation for different CD34+ subpopulations
  • Compensatory expansion of CD34- endothelial cells after ablation may mask the role of CD34+ endothelial cells

Cite This Study

Xie et al. (2023) studied Myocardial ischemia/reperfusion injury. Depletion of Cd34+ cells vs. Control mice was evaluated on Severity of ventricular fibrosis and cardiac function after ischemia/reperfusion injury. Depletion of Cd34+ cells alleviated the severity of ventricular fibrosis and improved cardiac function after ischemia/reperfusion injury.

synapsesocial.com/papers/6a9717c2934adeec1901fe4dhttps://doi.org/10.1007/s00395-023-00981-8
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Regulation of the Inflammatory Response in Cardiac Repair2012 · 1,209 citations
  2. 2The Role of Macrophages in the Infarcted Myocardium: Orchestrators of ECM Remodeling2019 · 119 citations
  3. 3Angiogenesis in the Infarcted Myocardium2012 · 255 citations
  4. 4Evolving Therapies for Myocardial Ischemia/Reperfusion Injury2015 · 1,018 citations
  5. 5Dynamic Interstitial Cell Response during Myocardial Infarction Predicts Resilience to Rupture in Genetically Diverse Mice2020 · 229 citations