Page 33 - GTM-2-1

Global Translational Medicine Stem cells in aortic aneurysm

Table 1. (Continued)
Species Diseases Number of Gender and Age (SD) Induction method Cell type Marker References
samples genotype
Homo MFS 3 patients, 4 1 male and 33.7 (9.3) years / SMC Smtn, Myh11 [48]
sapiens controls 2 females in in patients and Fibro Col1a1, Lum, Dcn
patients and 38 (10.7) years
all males in in controls EC Pecam11, Postn, Vwf
controls Mono/Macro Cd14, Cd68
CD8 T cell Cd8a, Cd8b
NK Klrc1
Mast Cpa3, Tpsb2
AAA: Abdominal aortic aneurysm; ATAA: Ascending thoracic aortic aneurysm; MFS: Marfan syndrome; TAAD: Thoracic aortic aneurysm and
dissection; AAD: Aortic aneurysm and dissection; F: Female; M: Male; WT: Wild type; NA: Not available; B APN: β-aminopropionitrile; Ang
II: Angiotensin II; HFD: High-fat diet; MSC: Mesenchymal stem cell; VSMC: Vascular smooth muscle cell; EC: Endothelial cell; Fibro: Fibroblasts;
Macro: Macrophages; Mono: Monocytes; DC: Dendritic cells; NK: Natural killer cells; Neutr: Neutrophils; Baso: Basophils; Eosin: Eosinophils;
Mast: Mast cells; Eryth: Erythrocyte

CD90, CD44, CD29, CD105, CD13, CD34, CD73, CD166, migrate and transdifferentiate into other cell types , and
[73]
CD10, CD49e, and CD59 are typical markers of ADSCs . have been extensively studied in vascular diseases such as
[66]
Earlier studies have shown that ADSCs positively regulate atherosclerosis . Similar recent studies on AA have found
[74]
the transformation of macrophages to the M2 phenotype that during AA formation, the contractile medial VSMCs
and inhibit the migration of neutrophils through paracrine are reprogrammed into MSC-like cells such as osteoblasts,
factors, thereby inhibiting the elastase-induced expansion chondrocytes, adipocytes, and macrophages. It was also
of mouse AAA. Recently, it has been discovered that the shown that VSMC reprogramming is driven, at least in part,
[67]
mechanism is that ADSC-derived exosomes (ADSC-exos) by increased expression of KLF4, KLF2, and KLF5, and that
and their microRNA-17-5p (miR-17-5p) inhibit AAA both conditions of hypercholesterolemia and loss of TGFβ
[75]
development . signaling are met . VSMCs can also be reprogrammed
[68]
to resident adventitial Sca1 progenitor cells (AdvSca1),
+
At the same time, ADSCs of AAA patients showed signs namely, AdvSca1-SM cells, induced by KLF4. The cells
of aging and decreased cellular function . It is reasonable mainly expressed genes related to hedgehog/WNT/beta-
[69]
to speculate that the occurrence of AA is somehow related catenin signaling and ECM, promoting pathological
to the failure of ADSC inhibition. Therefore, recovery of vascular remodeling and fibrosis, and the depletion of
ADSC function can be considered a method of AA therapy. KLF4 reduced AAA formation .
[76]
3.4. Vascular wall resident stem cells Multilineage differentiated persistent stress cells (Muse
There are many stem/progenitor cells presenting mainly cell), one of the subgroups of MSCs, are a special kind of
in the adventitia. When vascular injury happens, vascular adult stem cells that exist in bone marrow, connective tissue
stem/progenitor cells are mobilized and attributed to and peripheral blood, express markers of pluripotent stem
vascular repair. These adventitial progenitors express the cells and have the ability to self-renew and differentiate
markers, such as stem cell antigen-1 (Sca-1), c-Kit, CD34, into three germ layers. Compared with MSCs, Muse cells
[3]
and Flk1 . exhibited higher abilities of homing and migration to
damaged sites .
[77]
The Sca1 cells, mostly residing in the aortic wall,
+
produce growth factors and differentiate into fibroblasts 3.5. Induced pluripotent stem cells (iPSCs)
and neural/glial antigen 2 (NG2 ) cells, which contribute Induction of four transcription factors (Oct3/4, Sox2,
+
to aortic repair and remodeling . Bone marrow c-myc, and Klf4) by retroviral transfection reprograms
[70]
+
derived-CD34 stem cells, a type of vascular progenitor single somatic cells (non-germ cells) to a pluripotent state
cell, are involved in the formation of AA due to altered similar to embryonic stem cells, that is, induced pluripotent
blood flow . stem cells (iPSCs). iPSCs can further proliferate and
[71]
It is found that cardiovascular progenitor cells can also differentiate into many somatic cells, for example, vascular
[78]
differentiate into VSMCs through the SMAD3-dependent endothelial cells and VSMCs .
[72]
TGF-β signaling pathway . Numerous reports have At present, iPSCs have been applied in the research
demonstrated that VSMCs can dedifferentiate, proliferate, of TAA. VSMCs differentiated from Marfan syndrome
Volume 2 Issue 1 (2023) 8 https://doi.org/10.36922/gtm.v2i1.241