Histopathologic assessment of cultured human thymus.

Abstract

The maintenance and propagation of complex mixtures of cells in vitro in the form of native organs or engineered organoids has contributed to understanding mechanisms of cell and organ development and function which can be translated into therapeutic benefits. For example, allogeneic cultured postnatal human thymus tissue has been shown to support production of naïve recipient T cells when transplanted into patients with complete DiGeorge anomaly and other genetic defects that result in congenital lack of a thymus. Patients receiving such transplants typically exhibit reversal of their immunodeficiency and normalization of their peripheral blood T cell receptor V-beta repertoire, with long-term survival. This study was designed to assess the histopathologic changes that occur in postnatal human thymus slices when cultured according to protocols used for transplanted tissues. Results showed that as thymic organ cultures progressed from days 0 through 21, slices developed increasing amounts of necrosis, increasing condensation of thymic epithelium, and decreasing numbers of residual T cells. The architecture of the thymic epithelial network remained generally well-preserved throughout the 21 days of culture, with focal expression of cytokeratin 14, a putative biomarker of thymic epithelial cells with long-term organ-repopulating potential. All organ slices derived from the same donor thymus closely resembled one another, with minor differences in size, shape, and relative content of cortex versus medulla. Similarly, slices derived from different donors showed similar histopathologic characteristics when examined at the same culture time point. Taken together, these results demonstrate that diagnostic criteria based on structural features of the tissue identifiable via hematoxylin and eosin staining and cytokeratin immunohistochemistry can be used to evaluate the quality of slices transplanted into patients with congenital athymia.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1371/journal.pone.0230668

Publication Info

Hale, Laura P, Jadee Neff, Lynn Cheatham, Diana Cardona, M Louise Markert and Joanne Kurtzberg (2020). Histopathologic assessment of cultured human thymus. PloS one, 15(3). p. e0230668. 10.1371/journal.pone.0230668 Retrieved from https://hdl.handle.net/10161/24588.

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Scholars@Duke

Hale

Laura Pope Hale

Professor of Pathology

The Hale laboratory employs techniques of cellular and molecular biology to study mechanisms responsible for the generation of both normal immune responses and immune-mediated diseases. Research in the laboratory is mainly focused on inflammatory bowel disease (IBD), an immune-mediated disorder that is hypothesized to result from the abnormal immune response of a genetically susceptible host to the antigens derived from enteric bacteria. Development of optimal treatments for disease requires a detailed understanding of mechanisms of disease pathogenesis. Thus current work in the laboratory is aimed at understanding triggers of intestinal inflammation and mechanisms of inflammation-associated neoplasia, in addition to developing novel therapies for IBD treatment. Ongoing research also includes investigating mechanisms that determine the immunogenicity of oral antigens, to develop novel adjuvants for oral vaccines. This work has relevance for pathogenesis and treatment of infectious diseases affecting the gastrointestinal tract, as well as for inflammatory bowel disease.

Dr. Hale is an expert in pathologic evaluation of colitis and immunodeficiency in both humans and mice and is board-certified in Anatomic and Clinical Pathology.

Neff

Jadee Lee Neff

Assistant Professor of Pathology

As a diagnostic hematopathologist and molecular genetic pathologist, my clinical interests are focused on the histologic examination of tissue and bone marrow biopsies to diagnose hematologic malignancies (leukemia, lymphoma, myeloma, etc.) as well as testing DNA from tumors or from blood to detect inherited or acquired mutations that can guide therapeutic management and predict clinical outcome.  My research interests involve 1) understanding the biology of T-cell and NK-cell neoplasms; 2) defining the immunomodulatory response to neoplastic disease; 3) developing methods to monitor immune response and thereby refine tumor immunotherapy; and 4) exploring novel applications of tumor genetics in the diagnosis, prognosis, and management of cancer.

Cardona

Diana Marcella Cardona

Associate Professor of Pathology

I am active in translational research involving gastrointestinal/hepatobiliary pathology [specifically transplant related pathology (GVHD and rejection) and carcinogenesis of the pancreas] and bone and soft tissue malignancies [imaging techniques for intraoperative margin assessment].


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