A pilot in vivo model of human microcystic lymphatic malformations

Fang Hou, Yuemeng Dai, Lisa M. Buckmiller, Gal Shafirstein, Chun Yang Fan, Ali Saad, James Y. Suen, Gresham T. Richter

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: To develop an in vivo mouse model of human microcystic lymphatic malformations (LMs) and provide a tool for investigating the biological mechanisms and treatment of microcystic disease. Design: Animal model and histologic analysis. Setting: Tertiary referral center. Subjects: Fresh microcystic LM from human subjects were harvested and xenografted in the immunologically naïve nude mice (Athymic Nude-Foxn1 nu). Main Outcome Measures: Specimens were divided (5x5x5 mm) and secured in 4 quadrants subcutaneously along the dorsum of 4 nude mice. Weekly observations for volume, color, and texture of the grafts were performed with sequential harvesting from each quadrant at 30-day intervals. All grafts (n=16) were sectioned and stained with hematoxylin-eosin. Comparative pathologic evaluation of the grafts and native LM was performed by 2 blinded pathologists. Immunohistochemical analysis for D2-40 (a known lymphatic endothelial cell marker), Ki-67, and human-specific nuclear antigen was performed. Results: Near complete microcystic LM xenograft survival (n=13 [81%]) was achieved in the mouse irrespective of the period of implantation. Xenografts underwent a brief growth phase to day 20 to 30 and were quiescent until approximately day 65 but ultimately had a gradual loss of volume following transplant. Histologic analysis revealed structural characteristics matching the native LM tissue. Immunohistochemical analysis found that 10 (77%) of the surviving xenografts (77%) were positive for D2-40, 9 (69%) were positive for human-specific nuclear antigen, and 8 (62%) were positive for Ki-67. Conclusions: This preliminary in vivomodelsuggests that microcysticLMcansurvive in theathymicnudemouse.The presence of markers for human antibodies, lymphatic endothelium, and cellular proliferation demonstrates the stability of native tissue qualities within the xenografts.

Original languageEnglish (US)
Pages (from-to)1280-1285
Number of pages6
JournalArchives of Otolaryngology - Head and Neck Surgery
Volume137
Issue number12
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

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Heterografts
Transplants
Nuclear Antigens
Nude Mice
Lymphatic Endothelium
Lymphoid Tissue
Hematoxylin
Eosine Yellowish-(YS)
Tertiary Care Centers
Endothelial Cells
Animal Models
Color
Cell Proliferation
Outcome Assessment (Health Care)
Antibodies
Growth
Therapeutics

All Science Journal Classification (ASJC) codes

  • Otorhinolaryngology
  • Surgery

Cite this

Hou, F., Dai, Y., Buckmiller, L. M., Shafirstein, G., Fan, C. Y., Saad, A., ... Richter, G. T. (2011). A pilot in vivo model of human microcystic lymphatic malformations. Archives of Otolaryngology - Head and Neck Surgery, 137(12), 1280-1285. https://doi.org/10.1001/archoto.2011.203

A pilot in vivo model of human microcystic lymphatic malformations. / Hou, Fang; Dai, Yuemeng; Buckmiller, Lisa M.; Shafirstein, Gal; Fan, Chun Yang; Saad, Ali; Suen, James Y.; Richter, Gresham T.

In: Archives of Otolaryngology - Head and Neck Surgery, Vol. 137, No. 12, 01.12.2011, p. 1280-1285.

Research output: Contribution to journalArticle

Hou, F, Dai, Y, Buckmiller, LM, Shafirstein, G, Fan, CY, Saad, A, Suen, JY & Richter, GT 2011, 'A pilot in vivo model of human microcystic lymphatic malformations', Archives of Otolaryngology - Head and Neck Surgery, vol. 137, no. 12, pp. 1280-1285. https://doi.org/10.1001/archoto.2011.203
Hou, Fang ; Dai, Yuemeng ; Buckmiller, Lisa M. ; Shafirstein, Gal ; Fan, Chun Yang ; Saad, Ali ; Suen, James Y. ; Richter, Gresham T. / A pilot in vivo model of human microcystic lymphatic malformations. In: Archives of Otolaryngology - Head and Neck Surgery. 2011 ; Vol. 137, No. 12. pp. 1280-1285.
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abstract = "Objective: To develop an in vivo mouse model of human microcystic lymphatic malformations (LMs) and provide a tool for investigating the biological mechanisms and treatment of microcystic disease. Design: Animal model and histologic analysis. Setting: Tertiary referral center. Subjects: Fresh microcystic LM from human subjects were harvested and xenografted in the immunologically na{\"i}ve nude mice (Athymic Nude-Foxn1 nu). Main Outcome Measures: Specimens were divided (5x5x5 mm) and secured in 4 quadrants subcutaneously along the dorsum of 4 nude mice. Weekly observations for volume, color, and texture of the grafts were performed with sequential harvesting from each quadrant at 30-day intervals. All grafts (n=16) were sectioned and stained with hematoxylin-eosin. Comparative pathologic evaluation of the grafts and native LM was performed by 2 blinded pathologists. Immunohistochemical analysis for D2-40 (a known lymphatic endothelial cell marker), Ki-67, and human-specific nuclear antigen was performed. Results: Near complete microcystic LM xenograft survival (n=13 [81{\%}]) was achieved in the mouse irrespective of the period of implantation. Xenografts underwent a brief growth phase to day 20 to 30 and were quiescent until approximately day 65 but ultimately had a gradual loss of volume following transplant. Histologic analysis revealed structural characteristics matching the native LM tissue. Immunohistochemical analysis found that 10 (77{\%}) of the surviving xenografts (77{\%}) were positive for D2-40, 9 (69{\%}) were positive for human-specific nuclear antigen, and 8 (62{\%}) were positive for Ki-67. Conclusions: This preliminary in vivomodelsuggests that microcysticLMcansurvive in theathymicnudemouse.The presence of markers for human antibodies, lymphatic endothelium, and cellular proliferation demonstrates the stability of native tissue qualities within the xenografts.",
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