Coadministration of adipose-derived stem cells and control-released basic fibroblast growth factor facilitates angiogenesis in a murine ischemic hind limb model

详细信息    查看全文

• 作者：Hisako Horikoshi-Ishihara ; MD^a ; Morikuni Tobita ; DDS ; PhD^a ; Satoshi Tajima ; DDS ; PhD^a ; Rica Tanaka ; MD ; PhD^a ; Takashi Oshita ; MD^a ; Yasuhiko Tabata ; PhD ; DMedSc ; DPharm^b ; Hiroshi Mizuno ; MD ; PhD^a ; ^{hmizuno@juntendo.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 刊名：Journal of Vascular Surgery
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：64
• 期：6
• 页码：1825-1834.e1
• 全文大小：4024 K

文摘

Adipose-derived stem cells (ASCs) have angiogenic potential owing to their differentiation into endothelial cells and their release of angiogenic growth factors to elicit paracrine effects. In addition, control-released basic fibroblast growth factor (bFGF) sustained with a gelatin hydrogel also supports effective angiogenesis. We sought to determine if coadministration of ASCs and control-released bFGF into murine ischemic limbs facilitates angiogenesis.

Methods

Levels of growth factors in the conditioned media of ASCs cultured with or without control-released bFGF were measured by enzyme-linked immunosorbent assays. A murine ischemic hind limb model was generated and intramuscularly injected with the following: gelatin hydrogel (group 1), a high number of ASCs (group 2), control-released bFGF (group 3), a small number of ASCs and control-released bFGF (group 4), and a high number of ASCs and control-released bFGF (group 5). Macroscopic and microscopic vascular changes were evaluated until day 7 by laser Doppler perfusion imaging and histologic analyses, respectively.

Results

Secretion of hepatocyte growth factor, vascular endothelial growth factor, and transforming growth factor-β1 was enhanced by control-released bFGF. Vascular improvement was achieved in groups 4 and 5 according to laser Doppler perfusion imaging. Hematoxylin and eosin staining and CD31 immunohistochemical staining demonstrated an increase in the vascular density, vessel diameter, and thickness of vessel walls in groups 4 and 5. Cells positively stained for CD146, α-smooth muscle actin, and transforming growth factor-β1 were observed around vessel walls in groups 4 and 5.

Conclusions

These findings suggest that coadministration of ASCs and control-released bFGF facilitates angiogenesis in terms of vessel maturation in a murine ischemic hind limb model.