人脂肪干細胞與VEGF—PLGA納米微球緩釋系統構建工程化脂肪組織的相關研究

王永恒　李林瑞　雷雨

摘 要：目的 探討緩釋血管內皮生長因子復合支架與脂肪干細胞構建工程化脂肪的可行性。方法 制備VEGF-PLGA納米微球緩釋支架，檢測支架釋放 VEGF 濃度，體外提取培養 ADSCs，檢測復合支架對 ASC 生長增殖的影響。將復合支架和ADSCs植入裸小鼠背部，8 周后切取植入物稱重，組織切片HE染色，評估效果。結果 VEGF-PLGA納米微球緩釋復合支架能連續 12 d釋放較高濃度的VEGF，對 ADSCs的生長增殖無影響。動物實驗結果顯示復合支架與ADSCs共移植能顯著提高脂肪組織的形成，增加血管的生成（P<0.01），減少組織壞死。結論 VEGF-PLGA納米微球緩釋系統具有良好的生物安全性，其與ADSCs共移植構建工程化脂肪組織具有一定的可行性。

關鍵詞：血管內皮生長因子；緩釋支架；脂肪干細胞；工程化脂肪

中圖分類號：R622+.9 文獻標識碼：A DOI：10.3969/j.issn.1006-1959.2018.22.018

文章編號：1006-1959（2018）22-0064-03

Study on the Relationship between Human Adipose Stem Cells and VEGF-PLGA Nanospheres Slow-release System for Construction of Engineered Adipose Tissue

WANG Yong-heng1，LI Lin-rui1 ，LEI Yu2，HUO Bin-liang1，CAO Wei1

（ Department of Surgical Oncology1，Department of Oncology2，Shaanxi Provincial People's Hospital，Xi'an 710068，Shaanxi，China）

Abstract：Objective To investigate the feasibility of construction of engineered adipose tissue with sustained-release vascular endothelial growth factor（VEGF） composite stent and adipose stem cells.Methods VEGF-PLGA nanospheres sustained-release scaffolds were prepared and the concentration of VEGF was measured. ADSCs， was extracted in vitro to detect the effect of composite scaffolds on the growth and proliferation of ASC.The composite scaffold and ADSCs were implanted into the back of nude mice. After 8 weeks， the implants were weighed， and the tissue sections were stained with HE to evaluate the effect.Results VEGF-PLGA nanospheres sustained-release composite scaffolds could release higher concentration of VEGF， for 12 d without any effect on the growth and proliferation of ADSCs.The results of animal experiments showed that co-transplantation of composite scaffold and ADSCs could significantly increase the formation of adipose tissue， increase angiogenesis （P<0. 01）， and reduce tissue necrosis.Conclusion VEGF-PLGA nanospheres sustained-release system has good biological safety and it is feasible to co-transplant with ADSCs to construct engineered adipose tissue.

Key words：Vascular endothelial growth factor；Sustained-release scaffold；Adipose-derived stem cells；Engineered adipose tissue

脂肪干細胞 （adipose-derived stem cells，ADSCs）是來源于脂肪組織的一種間充質干細胞，具有多向分化潛能，其應用于乳房重建的優勢是組織來源充足、取材簡便，同時其無免疫排異的風險，能用于自體移植、同種異體移植，甚至異種移植[1]。臨床上常見有因乳房發育不良、腫瘤切除、外傷等原因引起的小乳癥、乳房的缺失等，可能引起患者嚴重的身心障礙。現有的乳房填充材料存在生物相容性差、結構穩定性差等缺點。尋找合適的乳房重建材料是目前乳腺外科研究的重點。自體脂肪組織是目前進行乳房填充和重建的最佳材料，但其來源受到很大限制，并且效果不穩定。自體脂肪顆粒移植存活率低，且易發生壞死、液化、纖維化、鈣化等，難以大量獲取，故難以廣泛應用。而隨著材料學的發展，各種緩釋支架的應用在為誘導干細胞分化、促進血管生成和增加血供并提高植入物的存活率提供了新的思路[2，3]。……