Microcirculatory Response In Vivo on Local Intraarterial Infusion of Autogenic Adipose-derived Stem Cells or Stromal Vascular Fraction

Abstract

Both adipose-derived stem cells (ASCs) and stromal vascular fraction (SVF) have been demonstrated to have regenerative properties with therapeutic potential for numerous diseases through local or topical applications. However, it is unclear whether ASC or SVF can be delivered systemically through an intra-arterial infusion. The purpose of this study was to examine the microcirculatory response in vivo on local intraarterial infusion of autogenic ASCs or SVF in a vascular pedicle isolated rat cremaster microcirculation model.

Materials and methods: Fat tissue was surgically harvested from the flanks of male Sprague-Dawley rats (n = 12) and processed for SVF isolation. Some SVF samples were cultured for 24 hours for ASC purification. The autogenic SVF (1 × 10⁵) cells (n = 6) or purified ASC (1 × 10⁵) cells (n = 6) cells were infused into the microcirculation of cremaster muscle at a speed of 0.05 mL/min through the cannulation of femoral artery. As this is a vascular pedicle isolated preparation, the infused SVF or ASC cells went nowhere but the cremaster muscle. The video image of the microcirculation was monitored in real time during infusion.

Results: Arteriole diameter was measured as A1 (100-160 µm), A2 (40-80 µm), and A3/A4 (10-30 µm). Capillary perfusion was quantified in 18 capillary fields of each muscle. There was a significant increase in the diameter of terminal arterioles (P = 0.049) and the capillary density (P = 0.02) after ASC intraarterial infusion. However, a significant cell aggregation, embolisms, and arterial obstruction were observed in the microcirculation in every case during SVF infusion.

Conclusions: Intraarterial infusion is an appropriate route for the delivery of autogenic ASCs, but not of SVF. SVF-induced microembolisms were the reason for narrowing or blocking the lumen of terminal arterioles, resulting in no flow in the corresponding capillaries.

Fig. 1.

The vascular pedicle isolated rat cremaster model used to investigate the microcirculatory response in vivo on local intraarterial delivery of autogenic ASC or SVF cells.

Fig. 2.

The microcirculatory response to intra-arterial delivery of autogenic ASCs and SVF. *Statistically significant differences (P < 0.05) from the baseline. **Statistically significant differences (P < 0.01) from the correspondent ASC groups.

Video Graphic 1.

See video, Supplemental Digital Content 1, which displays SVF intra-arterial infusion. Microembolisms were flowing within blood stream or sticking on the arteriole wall (A1) with vasoconstriction. At 2:40: embolisms were dropping from the bifurcation of A1 and A2 arterioles. At 2:50: embolisms narrowed or blocked the lumen of A3/A4 arterioles in many places resulting in no flow in the corresponding capillaries. This video is available in the “related videos” section of the full-text article on PRSGlobalOpen.com or available at http://links.lww.com/PRSGO/A272.

Video Graphic 2.

See video, Supplemental Digital Content 2, which displays the SVF intra-arterial bolus injection. At 0:07: a gentle bolus injection of SVF solution. At 1:00: embolisms blocked at the bifurcation of A1 and A2 arterioles, resulting in no flow in entire cremaster muscle. This video is available in the “related videos” section of the full-text article on PRSGlobalOpen.com or available at http://links.lww.com/PRSGO/A273.