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血管内皮生长因子 C 和脂肪来源干细胞对大鼠血管化淋巴结移植模型中淋巴管生成的影响。

The Effect of Vascular Endothelial Growth Factor C and Adipose-Derived Stem Cells on Lymphatic Regeneration in a Rat Vascularized Lymph Node Transfer Model.

机构信息

Department of Plastic Surgery, University Hospital Bulovka, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Department of Plastic Surgery, Third Faculty of Medicine, Teaching Hospital Královské Vinohrady, Charles University, Prague, Czech Republic.

出版信息

J Reconstr Microsurg. 2023 May;39(4):311-319. doi: 10.1055/a-1896-5471. Epub 2022 Jul 11.

DOI:10.1055/a-1896-5471
PMID:35817403
Abstract

BACKGROUND

Lymphedema is a chronic condition characterized by progressive edema with complicated treatment. Recently, new treatment strategies inducing lymphangiogenesis were proposed. The aim of our study was to examine the effect of vascular endothelial growth factor C (VEGF-C) and adipose-derived stem cells (ADSCs) on lymphatic regeneration and drainage re-establishment in vascularized lymph node transfer (VLNT) model using a pedicled vascularized lymph node (VLN) groin flap.

METHODS

Female Lewis rats with groin VLN flaps were utilized as a lymphedema model. Group A served as the control. Group B received VEGF-C. Group C received both VEGF-C and ADSCs. Group D received ADSCs only. Lymphatic drainage re-establishment was evaluated by ultrasound-photoacoustic imaging (US-PAI) after indocyanine green (ICG) injection.

RESULTS

The fastest regeneration of elevated flaps was observed in Groups B and C in all monitored periods. After the first month, ICG positivity was detected in 14.3% of animals in Group A, 71.43% of animals in Group B (odds ratio [OR] = 15;  = 0.048), and 83.33% in Group C (OR = 30;  = 0.027). On the contrary, the difference between control group and Group D (16.67%;  = 0.905) was statistically insignificant. Administration of VEGF-C, ADSC + VEGF-C, and ADSC led to full flap regeneration after 6 months. The control group had the lowest percentage of ICG positivity at all monitored time points.

CONCLUSION

We found that the fastest regeneration occurred with the combination of the VLN flap and VEGF-C. The addition of ADSC had an insignificant effect in our study. Furthermore, we proved the feasibility of PAI as an assessment tool of the lymphatic drainage recovery in a VLNT model.

摘要

背景

淋巴水肿是一种以进行性水肿为特征的慢性疾病,治疗复杂。最近,提出了新的诱导淋巴管生成的治疗策略。我们的研究目的是在带血管的淋巴结转移(VLNT)模型中使用带蒂血管化淋巴结(VLN)腹股沟皮瓣,研究血管内皮生长因子 C(VEGF-C)和脂肪来源干细胞(ADSCs)对淋巴管再生和引流重建的影响。

方法

使用雌性 Lewis 大鼠腹股沟 VLN 皮瓣作为淋巴水肿模型。A 组为对照组。B 组接受 VEGF-C。C 组同时接受 VEGF-C 和 ADSC。D 组仅接受 ADSC。吲哚菁绿(ICG)注射后,通过超声光声成像(US-PAI)评估淋巴引流重建情况。

结果

在所有监测期间,B 组和 C 组的抬高皮瓣再生最快。第一个月后,A 组动物中 ICG 阳性率为 14.3%,B 组动物中 ICG 阳性率为 71.43%(优势比[OR] = 15; = 0.048),C 组动物中 ICG 阳性率为 83.33%(OR = 30; = 0.027)。相反,对照组和 D 组(16.67%; = 0.905)之间的差异无统计学意义。给予 VEGF-C、ADSC+VEGF-C 和 ADSC 治疗 6 个月后,皮瓣完全再生。对照组在所有监测时间点的 ICG 阳性率最低。

结论

我们发现 VLN 皮瓣和 VEGF-C 的联合应用导致最快的再生。在我们的研究中,ADSC 的添加没有显著影响。此外,我们证明了 PAI 作为 VLNT 模型中淋巴引流恢复评估工具的可行性。

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