Adipose-derived Stem Cell Sheets Induce Angiogenesis and Hepatic Stellate Cell Activation.

BACKGROUND/AIM: Despite advances in critical care, postoperative liver failure remains a substantial complication of liver resection, with high mortality rates. Adipose-derived stem cells (ADSCs) have demonstrated potential in various regenerative applications; however, their precise mechanisms in liver repair remain unclear. This study investigated the effects of ADSC sheets on the vascular and cellular responses in a mouse model of partial hepatectomy.

MATERIALS AND

METHODS

Human ADSCs were cultured with magnetic nanoparticle-containing liposomes and formed multilayered cell sheets. Following partial hepatectomy in BALB/c nude mice, ADSC or collagen control sheets were attached to liver resection sites. Immunohistochemical analysis assessed angiogenesis (CD31), hepatic stellate cell activation (α-SMA), and cellular origin. Mice were sacrificed on postoperative days 4 and 7. Statistical analysis was conducted using Bonferroni's method (p<0.05).

RESULTS

Compared to cell-free collagen sheets (control), ADSC sheets demonstrated significantly enhanced neovascularization, with higher CD31 expression on postoperative days 4 and 7. Immunohistochemical analysis revealed that these CD31-positive cells were predominantly of mouse origin, rather than differentiated from transplanted human ADSCs, indicating host cell migration into the sheets. Additionally, ADSC sheets significantly increased α-SMA expression compared to that with collagen sheets, with expression levels progressively increasing from day 4 to 7, suggesting continuous activation of hepatic stellate cells. These findings indicate that ADSC sheets induce angiogenesis and hepatic stellate cell activation during liver regeneration, likely through paracrine mechanisms that recruit host cells, rather than through direct differentiation of transplanted ADSCs.

CONCLUSION

This study lays the groundwork for the clinical application of ADSC sheets, demonstrating their potential to enhance liver regeneration after hepatectomy by promoting host cell-mediated angiogenesis and hepatic stellate cell activation.