Multiple roles of CD34⁺ cell heterogeneity in cardiovascular injury and repair

doi:10.3969/j.issn.1674-8115.2025.12.012

Abstract

Abstract:

Cardiovascular injury and repair rely on the coordinated recruitment, proliferation, and differentiation of multiple cell types. As a heterogeneous cell population defined by the cluster of differentiation 34 (CD34) protein, CD34⁺ cells have long been regarded as key targets for cardiovascular regeneration and repair. These cells exhibit pronounced heterogeneity and pluripotent differentiation potential. Under the regulation of specific microenvironmental signals, they can differentiate into multiple lineages, such as endothelial cells, smooth muscle cells, fibroblasts, and inflammatory cells, thereby contributing to endothelial repair, tissue fibrosis, and immune modulation. In cardiovascular disease, CD34⁺ cells exert dual effects: they may facilitate tissue repair and regeneration while also potentially exacerbating pathological injury. Although CD34⁺ cell therapies have shown therapeutic promise in cardiovascular diseases, their clinical translation still faces numerous challenges and bottlenecks. Here, current evidence on the sources, differentiation trajectories, and functional heterogeneity of CD34⁺ cells is synthesized, and recent advances spanning basic research and clinical translation are summarized, with the aim of refining mechanistic understanding and informing the development of precise therapeutic strategies.

Key words: CD34? cell, cardiovascular disease, endothelial repair, endothelial progenitor cell, CD34⁺ cell therapy

CLC Number:

QIN Zihao, YUAN Hong, LU Yao, LENG Yiming. Multiple roles of CD34⁺ cell heterogeneity in cardiovascular injury and repair[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(12): 1662-1670.

Figures/Tables 4

TrendMD

References 79

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Cell subset	Distribution	Marker	Principal function
HSCs	Bone marrow, peripheral blood	Lin^-, CD34⁺, CD38^-, CD90⁺, CD45RA^-	Hematopoiesis and long-term reconstitution
EPCs	Bone marrow, peripheral blood, vascular intima, multiple organs	CD34⁺, CD133⁺, VEGFR2⁺, CD31⁺, VE-cadherin⁺, vWF⁺, CD45^-	Endothelial repair and angiogenesis
Inflammatory cells	Bone marrow, peripheral blood, tissues	CD45⁺	Immune responses and inflammation
Fibroblasts	Interstitium across organs	CD34⁺, PDGFRα⁺, PI16⁺ (mouse)	Matrix production, tissue repair, and regulation of fibrosis
Fibroblast progenitors	Multiple organs	CD34⁺ Sca1⁺(mouse), PI16⁺ (mouse), POSTN⁺	Differentiation into fibroblasts/myofibroblasts
SMCs	Multiple organs	αSMA⁺, MYH11⁺, SM22α⁺, CNN1⁺	Contractility and vascular tone, and remodeling in injury/fibrosis
SMPCs	Multiple organs	Sca1⁺ (mouse), CD34⁺, PDGFRβ⁺	Differentiation into SMCs and fibroblast-like lineages
MSCs	Bone marrow, adipose tissue, multiple organs	CD29⁺, CD44⁺, CD73⁺, CD90⁺, CD105⁺, CD34⁺	Osteogenic, chondrogenic, and adipogenic differentiation

Cell subset	Distribution	Marker	Principal function
HSCs	Bone marrow, peripheral blood	Lin^-, CD34⁺, CD38^-, CD90⁺, CD45RA^-	Hematopoiesis and long-term reconstitution
EPCs	Bone marrow, peripheral blood, vascular intima, multiple organs	CD34⁺, CD133⁺, VEGFR2⁺, CD31⁺, VE-cadherin⁺, vWF⁺, CD45^-	Endothelial repair and angiogenesis
Inflammatory cells	Bone marrow, peripheral blood, tissues	CD45⁺	Immune responses and inflammation
Fibroblasts	Interstitium across organs	CD34⁺, PDGFRα⁺, PI16⁺ (mouse)	Matrix production, tissue repair, and regulation of fibrosis
Fibroblast progenitors	Multiple organs	CD34⁺ Sca1⁺(mouse), PI16⁺ (mouse), POSTN⁺	Differentiation into fibroblasts/myofibroblasts
SMCs	Multiple organs	αSMA⁺, MYH11⁺, SM22α⁺, CNN1⁺	Contractility and vascular tone, and remodeling in injury/fibrosis
SMPCs	Multiple organs	Sca1⁺ (mouse), CD34⁺, PDGFRβ⁺	Differentiation into SMCs and fibroblast-like lineages
MSCs	Bone marrow, adipose tissue, multiple organs	CD29⁺, CD44⁺, CD73⁺, CD90⁺, CD105⁺, CD34⁺	Osteogenic, chondrogenic, and adipogenic differentiation