Decellularized tracheal extracellular matrix supports epithelial migration, differentiation, and function

Kutten, Johannes C., McGovern, David, Hobson, Christopher M., Luffy, Sarah A., Nieponice, Alejandro, Tobita, Kimimasa, Francis, Richard J., Reynolds, Susan D., Isenberg, Jeffrey S., and Gilbert, Thomas W. (2015) Decellularized tracheal extracellular matrix supports epithelial migration, differentiation, and function. Tissue Engineering Part A: Tissue Engineering, 21 (1-2). pp. 75-84.

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Abstract

Tracheal loss is a source of significant morbidity for affected patients with no acceptable solution. Interest in engineering tracheal transplants has created a demand for small animal models of orthotopic tracheal transplantation. Here, we examine the use of a decellularized graft in a murine model of tracheal replacement. Fresh or decellularized tracheas harvested from age-matched female donor C57BL/6 mice were transplanted into syngeneic recipients. Tracheas were decellularized using repeated washes of water, 3% Triton X-100, and 3 M NaCl under cyclic pressure changes, followed by disinfection with 0.1% peracetic acid/4% ethanol, and terminal sterilization by gamma irradiation. Tracheas were explanted for immunolabeling at 1, 4, and 8 weeks following surgery. Video microscopy and computed tomography were performed to assess function and structure. Decellularized grafts supported complete reepithelialization by 8 weeks and motile cilia were observed. Cartilaginous portions of the trachea were maintained in mice receiving fresh transplants, but repopulation of the cartilage was not seen in mice receiving decellularized transplants. We observed superior postsurgical survival, weight gain, and ciliary function in mice receiving fresh transplants compared with those receiving decellularized transplants. The murine orthotopic tracheal transplant provides an appropriate model to assess the repopulation and functional regeneration of decellularized tracheal grafts.

Item ID: 60714
Item Type: Article (Research - C1)
ISSN: 1937-335X
Funders: National Institutes of Health (NIH), American Heart Association (AHA), Institute for Transfusion Medicine, Hemophilia Center of Western Pennsylvania, Vascular Medicine Institute
Projects and Grants: NIH grant R01-HL108954, NIH grant R01-HL112914, NIH grant R21EB017184-01A1, NIH grant T32-GM008208, NIH grant T32-HL094295, AHA grant 11BGIA7210001
Date Deposited: 23 Oct 2019 12:36
FoR Codes: 06 BIOLOGICAL SCIENCES > 0606 Physiology > 060603 Animal Physiology Systems @ 35%
06 BIOLOGICAL SCIENCES > 0606 Physiology > 060602 Animal Physiology - Cell @ 35%
11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110203 Respiratory Diseases @ 30%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920115 Respiratory System and Diseases (incl. Asthma) @ 100%
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