Siba Haykal

The effect of decellularization of tracheal allografts on leukocyte infiltration and of recellularization on regulatory T cell recruitment

Tracheal transplantation without immunosuppressive therapy has been accomplished with a tissue-engineering approach using decellularized biological scaffolds in combination with recipient progenitor cells. The mechanisms of immune response directed towards these tracheal allografts have not been fully determined. In this study, we evaluated the immunogenicity of these grafts at the protein level, and functionally, in vitro and in vivo in a large animal model. Long-segment circumferential tracheal allografts were decellularized using two different protocols and recellularized using recipient mesenchymal stromal cells (MSC) and tracheal epithelial progenitor cells (TEC). Residual MHCI and MHCII immunostaining was found surrounding the submucosal glands despite cyclical decellularization. In an in vitro lymphocyte proliferation assay, CD4+ T cells continued to proliferate on decellularized pieces and this proliferation was inhibited by co-culture with autologous MSC. Allografts were heterotopically transplanted under a muscle flap in the neck of the recipients and decellularization was found to delay leukocyte infiltration but resulted in eventual cartilage degradation. Recellularization prevented this infiltration up to 3 weeks post-transplantation and allowed for preservation of the cartilage. The immune cells found within these grafts included a significant number of CD4+CD25+Foxp3+ regulatory T cells. Furthermore, gene expression of anti-inflammatory cytokines, such as IL-10 and TGF-β1, involved in proliferation, differentiation and function of regulatory T cells was found in these grafts. These results indicate that the immunological modification induced by recellularized tracheal scaffolds is an active process involving the recruitment of immunosuppressive cells, rather than simply the removal of donor-derived antigenic components.

Advances in Tracheal Reconstruction

Summary: A recent revival of global interest for reconstruction of long-segment tracheal defects, which represents one of the most interesting and complex problems in head and neck and thoracic reconstructive surgery, has been witnessed. The trachea functions as a conduit for air, and its subunits including the epithelial layer, hyaline cartilage, and segmental blood supply make it particularly challenging to reconstruct. A myriad of attempts at replacing the trachea have been described. These along with the anatomy, indications, and approaches including microsurgical tracheal reconstruction will be reviewed. Novel techniques such as tissue-engineering approaches will also be discussed. Multiple attempts at replacing the trachea with synthetic scaffolds have been met with failure. The main lesson learned from such failures is that the trachea must not be treated as a “simple tube.” Understanding the anatomy, developmental biology, physiology, and diseases affecting the trachea are required for solving this problem.

Infundibular carcinoma of the skin: a distinct morphological and immunohistochemical entity

This report describes a new entity which has been defined as infundibular carcinoma (IC) of the skin. This new entity must be distinguished from other basaloid carcinomas arising from the epidermis, the hair follicles or from sweat duct and glandular elements. Specific criteria have been used to define ICs. These include the macroscopic and the microscopic site of the tumour as well as its histomorphological and immunohistochemical patterns. A brief review of benign and malignant tumours of the pilar unit and the differential diagnosis of IC is also provided.

Proximal Forearm Transplantation for Below Elbow Amputations: Rationale and Surgical Technique

Proximal forearm replantation presents with multiple challenges. In this paper, we present the unique advantages of transplantation at the level of proximal forearm and contrast this to replantation. We describe the rationale for transplantation following below elbow amputation: the bone level allows fixation and preservation of the functioning elbow joint, and the muscle can be reconstructed above the elbow. The surgical procedure including anatomic dissections is also illustrated.

Determining the Immunogenicity and Structural Integrity of Decellularized Tracheal Allografts

INTRODUCTION: Diced cartilage have reemerged as a popular method in aesthetic rhinoplasty since Erol’s Turkish Delight technique. But an extensive literature indicates that the diced cartilage with Surgicel® wrapping absorbed and failed to correct the clinical problems. Recent studies showed that a significant foreign body reaction occurred in the diced cartilage grafts wrapped in Surgicel®, but not in those grafts wrapped in fascia. However, to date, no study has addressed the histologic behavior of wrapped diced cartilage using AlloDerm®. The main aim of this study was to compare the viability of diced cartilage wrapped in autogenous fascia and AlloDerm® in rabbits (1-3).