Human adipose-derived mesenchymal stem cell could participate in angiogenesis in a mouse model of acute hindlimb ischemia

Abstract

Introduction: Mesenchymal stem cells (MSCs) transplantation for the treatment of acute hindlimb ischemia is recently attracting the attention of many scientists. Identifying the role of donor cells in the host is a crucial factor for improving the efficiency of treatment. This study evaluated the injury repair role of xenogeneic adipose-derived stem cell (ADSC) transplantation in acute hindlimb ischemia mouse model.

Methods: Human ADSCs were transplanted into the limb of ischemic mouse. The survival rate of grafted cells and expression of human VEGF-R2 and CD31 positive cells were assessed in the mouse. In addition, the morphological and functional recovery of ischemic hindlimb was also assessed.

Results: The results showed that one-day post cell transplantation, the survival percentage of grafted cells was 3.62% ± 2.06% at the injection site and 15.71% ± 12.29% around the injection site. The rate of VEGFR2-positive cells had highest expression at 4 days post transplantation, 5.46% ± 2.13% at the injection site; 9.12% ± 7.17% at the opposite of injection site, and 7.22% ± 4.59% at the lateral gastrocnemius. The percentage of CD31 positive cells increased on day 4 at the injection site to 0.8% ± 1.60%, and further increased on day 8 at the lateral gastrocnemius site and the opposite injection site to 1.56% ± 0.44% and 1.17% ± 1.69%, respectively. After 14 days, the cell presentation and the angiogenesis marker expression were decreased to zero, except for CD31 expression at the opposite of injection site (0.72% ± 1.03%). Histological structure of the cell-injected muscle tissue remained stable as that of the normal muscle. New small blood vessels were found growing in hindlimb. On the other hand, approximately 66.67% of mice were fully recovered from ischemic hindlimb at grade 0 and I after cell injection.

Conclusion: Thus, xenotransplantation of human ADSCs might play a significant role in the formation of new blood vessel and can assist in the treatment of mouse with acute hindlimb ischemia.