Transplantation of adipose tissue-derived microvascular fragments promotes therapy of critical limb ischemia

脂肪组织微血管片段移植促进严重肢体缺血的治疗

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作者:Gyu Tae Park, Jae Kyung Lim, Eun-Bae Choi, Mi-Ju Lim, Bo-Young Yun, Dae Kyoung Kim, Jung Won Yoon, Yoon Gi Hong, Jae Hoon Chang, Seong Hwan Bae, Jung Yong Ahn, Jae Ho Kim

Background

Adipose tissue-derived microvascular fragments are functional vessel segments derived from arterioles, capillaries, and veins. Microvascular fragments can be used as vascularization units in regenerative medicine and tissue engineering containing microvascular networks. However, the in vivo therapeutic and vascularization properties of human microvascular fragments have not been investigated.

Conclusions

These results suggest that microvascular fragments show improved engraftment efficiency and vasculogenic activity in vivo and are highly useful for treating ischemic diseases and in tissue engineering. Adipose tissue-derived microvascular fragments are vascularization units in regenerative medicine and tissue engineering containing microvascular networks. Intramuscular injection of microvascular fragments markedly increased blood flow in the ischemic hindlimbs and alleviated tissue necrosis. The present study suggests that microvascular fragments show improved engraftment efficiency and vasculogenic activity in vivo and are highly useful for treating ischemic diseases and in tissue engineering.

Methods

In this study, we isolated microvascular fragments, stromal vascular fractions, and mesenchymal stem cells from human lipoaspirate and studied their therapeutic efficacy and in vivo vasculogenic activity in a murine model of hindlimb ischemia. In addition, in vivo angiogenic activity and engraftment of microvascular fragments into blood vessels were measured using Matrigel plug assay.

Results

Both microvascular fragments and stromal vascular fractions contain not only mesenchymal stem cells but also endothelial progenitor cells. In a Matrigel plug assay, microvascular fragments increased the number of blood vessels containing red blood cells more than mesenchymal stem cells and stromal vascular fractions did. The engraftment of the microvascular fragments transplanted in blood vessels within the Matrigel plug significantly increased compared to the engraftment of mesenchymal stem cells and stromal vascular fractions. Moreover, intramuscular injection of microvascular fragments markedly increased blood flow in the ischemic hindlimbs and alleviated tissue necrosis compared to that of mesenchymal stem cells or stromal vascular fractions. Furthermore, transplanted microvascular fragments formed new blood vessels in ischemic limbs. Conclusions: These results suggest that microvascular fragments show improved engraftment efficiency and vasculogenic activity in vivo and are highly useful for treating ischemic diseases and in tissue engineering. Adipose tissue-derived microvascular fragments are vascularization units in regenerative medicine and tissue engineering containing microvascular networks. Intramuscular injection of microvascular fragments markedly increased blood flow in the ischemic hindlimbs and alleviated tissue necrosis. The present study suggests that microvascular fragments show improved engraftment efficiency and vasculogenic activity in vivo and are highly useful for treating ischemic diseases and in tissue engineering.

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