Site-specific induction of lymphatic malformations in a rat model for image-guided therapy

Abstract

This model represents a promising tool for translational development of image-guided interventions for lymphatic malformations. It may also serve as a model for the study of lymphangiogenesis and the development of anti-lymphangiogenic therapies.

Congenital Lymphatic Malformations

“…12,[15][16][17][18][19] Identification of specific lymphatic markers, such as LYVE-1, D2-40, podoplanin, VEGF-C, and VEGF-D, has advanced the characterization of lymphatic tissue. 6,[19][20][21][22][23][24][25][26] An animal model of lymphatic malformations, induced via intraperitoneal injection of Freund's incomplete adjuvant, may enable further studies on endovascular therapies for these lesions. 24 In contrast, intraperitoneal injection of Freund's incomplete adjuvant resulted in a vascularized oil granuloma rather than a lymphatic malformation.…”

“…6,[19][20][21][22][23][24][25][26] An animal model of lymphatic malformations, induced via intraperitoneal injection of Freund's incomplete adjuvant, may enable further studies on endovascular therapies for these lesions. 24 In contrast, intraperitoneal injection of Freund's incomplete adjuvant resulted in a vascularized oil granuloma rather than a lymphatic malformation. 25 Histologically, lymphatic malformations are thinwalled fluid-filled cysts with surrounding connective tissue-containing stroma.…”

Preliminary investigation of human lymphatic malformations in vitro

“…Currently, a universally accepted model for human LM is not available for experimental investigation. In a recent study, Short and colleagues23 reported an in vivo rat model of LM that was created using intraperitoneal injection of Incomplete Freund's Adjuvant. LM were detected in the abdomen and neck by ultrasound near 45 days postinduction.…”

Lymphangiogenesis:in vitroandin vivomodels

“…LECs for cultures were also isolated from lymphangiomas, which are lesions induced by incomplete Freund's adjuvant injection into the peritoneal cavity of mice (40) or rats (41). Lymphatic vessels from this lesion are mechanically disrupted, and LEC is enzymatically isolated before seeding onto a 2-D substrate (42,43) or being embedded in a fibrin gel for 3-D cultures (44).…”