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

Filip Jonas; Peter Kesa; Petr Paral; Jan Pankrac; Marie Hubalek Kalbacova; Jakub Miletin; Andrej Sukop; Martin Molitor; Krystof Stanek; Ludek Sefc; Ondrej Mestak

doi:10.1055/a-1896-5471

Journal of Reconstructive Microsurgery, Inhaltsverzeichnis

J Reconstr Microsurg 2023; 39(04): 311-319
DOI: 10.1055/a-1896-5471

Original Article

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

Filip Jonas

¹Department of Plastic Surgery, University Hospital Bulovka, First Faculty of Medicine, Charles University, Prague, Czech Republic

²Department of Plastic Surgery, Third Faculty of Medicine, Teaching Hospital Královské Vinohrady, Charles University, Prague, Czech Republic

,

Peter Kesa

³Center for Advanced Preclinical Imaging (CAPI), First Faculty of Medicine, Charles University, Prague, Czech Republic

,

Petr Paral

³Center for Advanced Preclinical Imaging (CAPI), First Faculty of Medicine, Charles University, Prague, Czech Republic

,

Jan Pankrac

³Center for Advanced Preclinical Imaging (CAPI), First Faculty of Medicine, Charles University, Prague, Czech Republic

,

Marie Hubalek Kalbacova

⁴Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic

,

Jakub Miletin

²Department of Plastic Surgery, Third Faculty of Medicine, Teaching Hospital Královské Vinohrady, Charles University, Prague, Czech Republic

,

Andrej Sukop

²Department of Plastic Surgery, Third Faculty of Medicine, Teaching Hospital Královské Vinohrady, Charles University, Prague, Czech Republic

,

Martin Molitor

¹Department of Plastic Surgery, University Hospital Bulovka, First Faculty of Medicine, Charles University, Prague, Czech Republic

,

Krystof Stanek

¹Department of Plastic Surgery, University Hospital Bulovka, First Faculty of Medicine, Charles University, Prague, Czech Republic

,

Ludek Sefc

³Center for Advanced Preclinical Imaging (CAPI), First Faculty of Medicine, Charles University, Prague, Czech Republic

,

Ondrej Mestak

¹Department of Plastic Surgery, University Hospital Bulovka, First Faculty of Medicine, Charles University, Prague, Czech Republic

› Institutsangaben

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; p = 0.048), and 83.33% in Group C (OR = 30; p = 0.027). On the contrary, the difference between control group and Group D (16.67%; p = 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.

Keywords

VEGF - ADSC - vascularized lymph node transfer - VLNT - lymphatic regeneration

Volltext

Referenzen

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