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Partial decellularization eliminates immunogenicity in tracheal allografts.

ABSTRACT: There is currently no suitable autologous tissue to bridge large tracheal defects. As a result, no standard of care exists for long-segment tracheal reconstruction. Tissue engineering has the potential to create a scaffold from allografts or xenografts that can support neotissue regeneration identical to the native trachea. Recent advances in tissue engineering have led to the idea of partial decellularization that allows for the creation of tracheal scaffolds that supports tracheal epithelial formation while preserving mechanical properties. However, the ability of partial decellularization to eliminate graft immunogenicity remains unknown, and understanding the immunogenic properties of partially decellularized tracheal grafts (PDTG) is a critical step toward clinical translation. Here, we determined that tracheal allograft immunogenicity results in epithelial cell sloughing and replacement with dysplastic columnar epithelium and that partial decellularization creates grafts that are able to support an epithelium without histologic signs of rejection. Moreover, allograft implantation elicits CD8+ T-cell infiltration, a mediator of rejection, while PDTG did not. Hence, we establish that partial decellularization eliminates allograft immunogenicity while creating a scaffold for implantation that can support spatially appropriate airway regeneration.

SUBMITTER: Tan ZH

PROVIDER: S-EPMC10487308 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Partial decellularization eliminates immunogenicity in tracheal allografts.

Tan Zheng Hong ZH Liu Lumei L Dharmadhikari Sayali S Shontz Kimberly M KM Kreber Lily L Sperber Sarah S Yu Jane J Byun Woo Yul WY Nyirjesy Sarah C SC Manning Amy A Reynolds Susan D SD Chiang Tendy T

Bioengineering & translational medicine 20230421 5

There is currently no suitable autologous tissue to bridge large tracheal defects. As a result, no standard of care exists for long-segment tracheal reconstruction. Tissue engineering has the potential to create a scaffold from allografts or xenografts that can support neotissue regeneration identical to the native trachea. Recent advances in tissue engineering have led to the idea of partial decellularization that allows for the creation of tracheal scaffolds that supports tracheal epithelial f ...[more]

PMID: 37693070

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Project description:BackgroundMany studies have shown that mucosa-treated tracheas can be used for allotransplantation without the use of immunosuppressants. However, no literature has reported whether the transplanted trachea has normal biomechanics. In this study, fresh dog trachea was used as a control to determine the mechanical properties of allograft trachea after mucous membrane removal.MethodsCervical tracheas (~10 cm in length, consisting of the cartilage rings down to the tracheal carina) and the surrounding connective tissues were removed from 20 mixed-breed dogs and then divided into 4 groups with 5 samples in each group. The groups were defined as follows: group A, fresh canine tracheas without any treatment; group B, canine tracheas after sodium dodecyl sulphate (SDS) de-epithelialization; group C, canine tracheas implanted into the dorsal fascia of beagle dogs for 1 month after SDS de-epithelialization; group D, canine tracheas implanted into the dorsal fascia of beagle dogs for 6 months after SDS de-epithelialization. All heterotopically implanted beagle dogs were free of any immunosuppressive treatment. Uniaxial tensile (n=20) and compressive (n=20) experiments were performed on the 4 groups of trachea using a universal testing machine; the tensile load was recorded at 150% of the original tracheal length (50% displacement), and the compressive load was recorded at 50% of the initial anteroposterior diameter (50% displacement). The average difference in tensile and compressive loads between groups was compared by analysis of variance.ResultsNo significant difference was found in the mean compressive strength among groups (group A =2.38±0.87 N, group B =3.33±1.03 N, group C =5.39±2.44 N, group D =3.04±2.12 N; P=0.07 for all groups). The mean tensile strength of group C was 9.68±0.86 N, resulting in a significant difference in tensile strength compared to group A (22.51±3.91 N) and B (24.24±7.46 N) (P<0.001). No significant difference in tensile strength was observed among groups A, B, and D.ConclusionsThe de-epithelialized trachea showed no significant change in mechanical properties after 6 months of implantation.

Project description:OBJECTIVES AND DESIGN:At the present time there are two waiting list for patients with vascular prosthetic infection indicated for arterial transplantation in the Czech Republic. The inclusion of each patient for cold-stored or cryopreserved arterial transplantation is the preference of indicating surgeon. In this experimental work we studied the immunogenicity of rat aortal allografts treated by our new clinical cryopreservation/slow thawing protocol. MATERIAL AND METHODS:Brown-Norway (BN) (N = 6, 203-217 g) or Lewis (LEW) (N = 6, 248-254 g) abdominal aortal grafts treated in accordance with our new clinical cryopreservation/slow thawing protocol were orthotopically transplanted to Lewis recipients (N = 12, 191-245 g). Aortal wall histology and infiltration by recipient immune cells, as well as donor specific anti MHC class I and II antibodies in recipient serum were studied in both isografts and allografts on day 30 postransplant. Core data of cryopreserved allografts were compared to our previous data of cold-stored aortal allografts treated in accordance with our clinical cold-storage protocol. RESULTS:Cryopreserved allografts showed regular morphology of aortal wall with clear differentiation of all three basic anatomical layers on day 30 postransplant. Intimal layer showed no hyperplasia, luminal surface was covered by endothelial cells. No statistical difference was observed in tunica media thickness between isografts and allografts. The medial layer showed no necrosis, shrinkage or immunoglobuline G deposition in any experimental group. The adventitial infiltration by immune cells was significantly higher (P<0.05) in allografts. Cryopreserved allografts showed significant lower activation of both cell- and antibody mediated immunity compared to historical data of cold-stored allografts. CONCLUSION:Aortal wall histology of rat allografts treated by our new standardized clinical cryopreservation/slow thawing protocol was comparable to that of the cryopreserved isografts on day 30 posttranspant. The immunogenicity of cryopreserved aortal allografts was significantly lower compared to that of cold-stored aortal allografts.

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Partial decellularization eliminates immunogenicity in tracheal allografts.

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Partial decellularization eliminates immunogenicity in tracheal allografts.

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