Revista de medicina regenerativa

Stem Cell Therapy for Aortic Aneurysm: Does the Administered Cell Type Influence the Therapeutic Effects?

Yamawaki-Ogata A, Fujimoto KL, Mutsuga M, Tokuda Y, Usui A; Narita Y

Objective: We previously demonstrated that Mesenchymal Stem Cells (MSCs) represent a novel alternative therapeutic tool for treatment of aortic aneurysm (AA). MSCs can be obtained from Bone Marrow (BM) and Adipose Tissue (AD), but the cells from these two sources have different characteristics. In this study, we examined BM-MSCs, AD-MSCs, and Dermal Fibroblast (D-FBs) in order to determine the appropriate sources of cells for treatment of AA. Methods: We compared cell proliferation, population doubling time (PDT), cell surface markers, and trophic proteins among the three cell types. We then evaluated AA diameter, medial elastin area, existence rate of AA, and MMP-2 and -9 activities following intravenous injection of each type of cells into angiotensin IIinduced AA mice. Results: BM-MSCs yielded higher cell numbers and had a shorter PDT than the other cell types. Positivity for the cell surface markers of Sca-1, PDGFR-α, CD44, CD73, CD105, and CD106 was no significant difference among the three cell types. Protein arrays revealed that proteins including Activin A, adiponectin-like 3, Dkk-1, IL-10, IL-13, secretory leukocyte protease inhibitor (SLPI), progranulin, TGF-β1 and TIMP-2 were differentially expressed at least >2-fold in BM-MSCs relative to AD-MSCs and D-FBs. Aortic diameters, the existence rate of AA, and the activities of MMP-2 and -9 were most reduced in the BM-MSC group. Conclusion: BM-MSCs exhibited higher levels of proliferation and secretion of factors involved in anti-inflammatory effects, immunosuppression, ECM synthesis, and MMP inhibition than ADMSCs and D-FBs. These results indicate that BM-MSCs are a more effective treatment for AA than AD-MSCs and D-FBs.