Mesenchymal stem cells for treatment of aortic aneurysms

Table 1 Mesenchymal stem cells phenotypic characteristics

		Positive marker	Negative marker	Pluripotency	Ref.
ISCT criteria	Human MSC	CD73, CD90, CD105	CD34, CD45, CD11b or CD14, CD19 or CD79α, HLA-DR	Osteogenic Chondrogenic Adipogenic	[38]
In AA experimental studies	Mouse BM-MSC	CD44, CD106, Sca-1	CD11b, CD31, CD34, CD45, CD86, CD117	Osteogenic Chondrogenic Adipogenic	[51,53]
	Human placental-MSC	CD29, CD44, CD73, CD90, CD105	CD14, CD19, CD34, CD45, HLA-DR	Data not shown	[54]
	Rat BM-MSC	CD44, CD73, CD90, CD105	CD11b, CD45	Data not shown	[56]
	Pig ASC	CD73, CD90, CD105	CD14, CD11b	Osteogenic Chondrogenic Adipogenic	[57]
	Pig BM-MSC	CD13, CD29	CD31, CD34, CD45	Data not shown	[58]

ISCT: International society of cell therapy; MSC: Mesenchymal stem cell; AA: Aortic aneurysm; BM-MSC: Bone marrow-derived MSC; HLA-DR: Human leukocyte antigen-DR; ASC: Adipose tissue-derived MSC.

Table 2 Animal studies for treatment of aortic aneurysmusing mesenchymal stem cells

Experimental AA model	Cell source	Number of cells	Injection time	Delivery	Efficiency	Ref.
ATII-infusion mouse model	BM-MSC	Cell-sheet	Same time as ATII-infusion	Implantation of MSC-sheet around infrarenal aorta	4 wk after implantation, inhibition of AA development and growth, and elastin degradation downregulation of IL-1β, IL-6, MCP-1 and TNF-α protein expression, and MMP-2 and -9 enzymatic activity Up-regulation of IGF-1 and TIMP-1 protein expression Positive for MSC specific surface marker	[51]
ATII-infusion mouse model	BM-MSC	1 × 106/every week, 4 times	Same time as ATII-infusion	iv-administration	4 wk after injection, inhibition of AA development and growth, elastin degradation, M infiltration downregulation of IL-1β, IL-6 and MCP-1 protein expression, and MMP-2 and -9 enzymatic activity Up-regulation of IGF-1 and TIMP-1 protein expression Detection of MSC in the aortic wall	[53]
Elastase-perfusion mouse model	Placental-MSC	1 × 106	1 d after elastase-perfusion	iv injection	2 wk after injection, inhibition of AA expansion, inflammatory cell infiltration, and elastin degradation, downregulation of IL-17, IL-23, INF-γ, TNF-α, RANTES and MCP-1 protein expression Increase of α-SMA expression	[54]
Xenograft rat model	BM-MSC	1 × 106	Same time as surgical intervention	Catheter	1 wk after surgical intervention inhibition of inflammatory cells infiltration and MMP-9 gene expression, and increase of TIMP-1 gene expression, after 4 wk, inhibition of AA expansion, increase of α-SMA expression, elastin and collagen content	[56]
Dacron-patch pig model	ASC	1 × 106	Same time as surgical intervention	Catheter	Attenuation of inflammation reaction, detection of ASC 3 wk after surgical intervention	[57]
Balloon injury with type 1 collagen and elastase-perfusion porcine model	BM-MSC	1 × 106	Same time as balloon-injury	Direct injection into aortic wall	72 h after injection, Increase of VEGF-A mRNA expression level 1 wk after injection, detection of GFP-labeled MSC at aortic wall and vWF positive cells formed tubuloluminal structures within outer layer of media and throughout the adventitia	[54]

AA: Aortic aneurysm; ATII: Angiotensin II; MSC: Mesenchymal stem cell; BM-MSC: Bone marrow-derived MSC; iv: Intravenous; VEGF: Vascular endothelial growth factor; GFP: Green fluorescent protein; TIMP-1: Tissue inhibitor of metalloproteinase 1; MMP: Matrix metalloproteinases; MCP-1: Monocyte chemotactic protein 1; IL: Interleukin; TNF: Tumor necrosis factor; IGF: Insulin-like growth factor; IFN: Interferon; ASC: Adipose tissue-derived MSC; vWF: von Willebrand factor.

Table 3 Methodology of delivery system

Delivery system	Administration site	Localization, timing	Delivery system		Ref.
			Merits	Demerits
Cell-sheet	Adventitia of abdominal aorta	Adventitia, 4 wk after implantation	High targeting ability	Invasive procedure by laparotomy	[51]
iv	Tail vein	Media and/or adventitia, at 4 wk	Least invasive	Low targeting ability and trapping in other tissue	[53]
iv	Tail vein	Data not shown	Least invasive	Low targeting ability and trapping in other tissue	[54]
Catheter	Clamped endovascular	Intima 1 wk after injection	Less invasive and high targeting ability	Requirement of a surgical procedure or advanced catheter intervention	[56]
Catheter	Clamped endovascular	Media 3 wk after injection	Less invasive and high targeting ability	Requirement of a surgical procedure or advanced catheter intervention	[57]
Direct injection	Injured aortic wall	Aortic wall, 1 wk after injection	High targeting ability	Risk of rupture	[58]

iv: Intravenous.