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Global Translational Medicine                                               Stem cells in aortic aneurysm



































            Figure 2. Potential applications of the patient somatic cell-derived hiPSC. The iPSC was derived from the patient’s somatic cells. On the one hand, iPSC
            derived from the disease-affected cells could be directly differentiated into VSMC and EC for disease modeling, drug screening, clinical trials and cohort
            studies for targeted validation. On the other hand, iPSC after gene correction could be used for vascular transplantation and cell transplantation for
            autologous therapy.

            patients-derived  iPSCs,  showing  Fbn1  mutation,  TGF-β   disease models, drug screening, and clinical trials of AA
            signaling activation, decreased contractility and increased   treatment. Gene modification is used for revascularization
            apoptosis, was applied as a TAA disease model. The   or cell transplantation in the treatment of AA.  Figure  2
            disease phenotype of MFS-iPSC-VSMCs was corrected   shows the origin, differentiation and application of iPSCs
            by CRISPR/Cas9 gene editing, indicating that the  Fbn1   in patients.
            mutation is the main cause of Marfan syndrome. It is
            found that TGF-β inhibitor can inhibit the accumulation   4. Treatment and clinical application
            of fibrillin1 and the abnormal expression of MMPs .  If the AA is not treated promptly, the risk of progressive
                                                    [79]
              iPSCs have also been shown to differentiate into a   expansion, rupture, and even death is significantly high.
            variety of cell types. To date, endothelial cells, EPCs and   Thus, large AA at risk is usually treated immediately
            MSCs have been successfully differentiated from human   with surgical treatment. Nonsurgical treatment like
            iPSCs. And the MSCs generated from iPSC had stronger   pharmacological treatment is beneficial for small AA .
                                                                                                           [84]
            proliferation ability and telomerase activity . Based on   Specific ways to treat AA are shown in Figure 3.
                                               [80]
            this, some researchers propose to combine iPSC technology
            with clinical research and pharmacogenetics to determine   Due to their various types and functions, recent studies
            the best treatment method for each patient according to   have reported that stem cells also have a certain application
            individual differences . In addition to Marfan syndrome,   value in the treatment of AA. Researches on EPCs
                             [81]
            other TAA syndromes such as Loeys Dietz syndrome   mainly focused on the mechanism of AA pathogenesis
            can also be investigated using iPSC technology to study   and recovery, but it still has great potential for clinical
            the disease mechanism . At present, EPCs and vascular   application. The  number  of  EPCs  doubled  14  days after
                               [82]
            endothelial cells can also be differentiated from iPSCs, and   internal aneurysm repair (EVAR), which may be used
            further studied for mechanism research and therapeutic   to predict AA development and evaluate post-treatment
                                                                     [55]
            applications .                                     efficacy .
                     [83]
              iPSCs have a wide range of clinical applications. Somatic   It has been demonstrated that intravenous or peripheral
            cells are extracted from patient tissues and reprogrammed   delivery of MSCs can inhibit elastase-induced AA
            to obtain iPSCs. The iPSCs can be further differentiated   expansion in animal models. MSC implantation inhibits
            into VSMCs and endothelial cells, which can be used for   Ang II-induced AA development in apoE   mice by
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            Volume 2 Issue 1 (2023)                         9                      https://doi.org/10.36922/gtm.v2i1.241
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