A review of current status of cell-based therapies for aortic aneurysms

Yamawaki-Ogata, Aika; Mutsuga, Masato; Narita, Yuji

doi:10.1186/s41232-023-00280-8

Inflammation and Regeneration

Table 1 Cell-based therapies for treatment of AA

From: A review of current status of cell-based therapies for aortic aneurysms

Cell source	Cells	Species	Model	Delivery	Outcome	Ref.
BM-MSCs	1 × 10⁶	Mouse	Angiotensin II	IV	AAA diameter ↓ IL-6 and MCP-1 ↓ MMP-2 and -9 ↓ M1 macrophages infiltration ↓ IGF-1 and TIMP-2 ↑ Preserved elastin structure	[37, 38]
BM-MSCs or VSMCs	1 × 10⁶	Guinea pig	Xenograft rat model	Catheter	AAA expansion ↓ MMP-9 ↓ Macrophages infiltration ↓ BM-MSCs had more powerfully than VSMCs	[39]
Male or female BM-MSCs	3 × 10⁶	Mouse	Elastase	IV	In female MSCs AAA growth ↓ TNF-α, IL-1β, and MCP-1 ↓ Female MSCs most strongly attenuated AAA growth	[40]
AD-MSCs	4 × 10⁶	Rat	CaCl₂	Carotid artery injected	Elastin expression in SMCs ↑ Reconstruction of elastic fiber	[41]
Muse cells	2 × 10⁴	Mouse	CaCl₂ and elastase	IV	AAA dilation ↓ Preserved elastic fibers Spontaneous differentiation into ECs and SMCs	[42]
SPCs	1 × 10⁷	Rabbit	CaCl₂ and elastase	Subadventitially injected	In LOX gene-modified SPCs AAA progression ↓ MMP-2 and -9 ↓ Preserved elastin structure	[43]
UC-MSCs	1 × 10⁶	Mouse	Elastase	IV	AAA formation ↓ HMGB1 and IL-17 ↓ MMP2 and MMP9 ↓	[44]
AD-MSCs	1 × 10⁶	Mouse	Elastase	IV	AAA expansion ↓ Aortic site CD206⁺ M2 macrophages ↑ Tregs ↑ CD4⁺CD28⁻ T cells ↓ CD8⁺CD28⁺ T cells ↓ Ly6G/C⁺ neutrophils ↓ Circulating CD115⁺CXCR1⁻LY6C⁺ activated monocytes ↓	[43]
UC-MSCs	1 × 10⁶	Rat	Elastase	IV	AAA expansion ↓ Elastin degradation ↓ MMPs, TNF-α ↓ Preserved and/or restored VSMC contractile phenotype	[45]
Allogeneic BM-MSCs	1 × 10⁶	Mouse	Angiotensin II	IV	Aortic diameter ↓ MMP-2 and -9, IL-6, MCP-1 ↓ M1 macrophages infiltration ↓ IGF-1, TIMP-2 ↑ Preserved elastin structure	[46]
UC-MSCs	1 × 10⁶	Mouse	Elastase	IV	TAA formation and expansion ↓ Infiltration of macrophages, T cells, neutrophils ↓ miRNA-10a, -29b, 24 ↑ CXCL-13/BCA-1, CXCL12, CXCL10, CCL5, and IL27 ↓ IL-10 ↑	[44]
VSMCs or iPSC-SMP	5 × 10⁵	Mouse	Elastase	Porous collagen scaffolds	In the SMC-seeded scaffold group AAA expansion ↓ In both the SMC- and iPSC-SMP-seeded scaffold groups SMC retention ↑ Macrophage invasion ↓	[47]
AD-MSCs	1 × 10⁶	Pig	Collagenase and elastase	Gel foam	AAA dilation ↓ Collagen and elastin ↑ α-SMA ↑ VEGF, TIMP1, and MMP3 ↑	[48]
M2 macrophages differentiated from J774A.1 cell line	1 × 10⁶	Mouse	Angiotensin II	IP	Aneurysmal expansion ↓ M1/M2 ratio ↓ IL-1β, IL-6, and MCP-1 ↓ IL-4 and IL-10 ↑ Elastin degradation ↓ Injected cells maintained the M2 phenotype throughout 28 days	[49]

Abbreviations: AAA Abdominal aortic aneurysm, AD Adipose derived, BM Bone marrow, MSCs Mesenchymal stem cells, VSMCs Vascular smooth muscle cells, iPSC-SMP pluripotent stem cell-derived smooth muscle progenitor cells, IV Intravenous injection; IP Intraperitoneal injection, α-SMA α-smooth muscle actin, HMGB1 High mobility group box 1, IGF-1 Insulin-like growth factor-1, IL Interleukin, MCP-1 Monocyte chemoattractant protein-1, MMP Matrix metalloproteinase, Muse cells Multilineage-differentiating stress-enduring cells, SPCs Smooth muscle progenitor cells, TAA Thoracic aortic aneurysm, TIMP Tissue inhibitor of metalloproteinase, TNF-α Tumor necrosis factor-α, UC Umbilical cord, VEGF Vascular endothelial growth factor

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ISSN: 1880-8190

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