Abstract

This study aimed to investigate the survival and efficacy indicators of human thyroid tissue transplantation into a retrievable, prevascularized implanted Sernova Corp Cell Pouch™ (CP) device. Thyroid tissue from human donors was transplanted subcutaneously into the pre-implanted CP device or into the subcutaneous (SC) space alone as a control in a nude Mus musculus model. Transplanted M. musculus were monitored for human serum thyroglobulin (TG) levels for 3 months until the transplants were removed for histological assessment. Human thyroid tissue survived and continued to produce TG in transplanted nude M. musculus in the CP, with no adverse events. CP transplants exhibited more persistent and robust production of human TG than tissue placed in the SC space alone from 3 to 13 weeks post transplantation. Fresh thyroid transplants had better survival and function compared to cryopreserved transplants. Thyroid transplant viability correlated with TG levels at 3 months post-transplant (p = 0.03). Immunofluorescence staining of transplants for TG and TPO localized in thyroid follicles. Human thyroid tissue transplanted into the subcutaneously implanted pre-vascularized CP in nude M. musculus survived and continued to produce robust and persistent human TG and warrants further investigation as a treatment for postoperative hypothyroidism.

Highlights

  • Hypothyroidism is the predictable consequence of total thyroidectomy, and after hemithyroidectomy an estimated 20% of patients will eventually go on to become hypothyroid [7]

  • Achieving a normal serum TSH level in patients receiving LT4 monotherapy may be complex because it is impacted by many different factors that include: compliance, consistency of clinical monitoring, food intake, medications, renal T4 loss, gastrointestinal malabsorption, pregnancy, body weight, sex, age and even the presence of antibodies that interfere with TSH measurement [12]

  • One possible reason for persistent symptoms is differences in the inter-individual hypothalamic-pituitary-thyroid axis ‘set-point’ for circulating thyroid hormone concentrations. Another possible explanation is based on the observation that for individuals with an intact thyroid gland approximately 20% of their circulating T3 comes from intrathyroidal deiodination of T4 and/or direct thyroidal secretion, and 80% comes from peripheral T4 conversion by deiodinases. This is not the case for hypothyroid individuals on LT4 monotherapy in whom all T3 is derived from peripheral LT4 conversion [1]

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Summary

Introduction

Thyroid hormone replacement after thyroidectomy involves daily administration of levothyroxine (LT4) with dose adjustment based primarily on laboratory measurement of thyroid function (thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine. Transplantation of human thyroid tissue into a Cell PouchTM design, data collection and analysis, decision to publish, or preparation of the manuscript. Materials and expertise were received from Sernova Corp. Employees and/or affliates of Sernova are coauthors of this manuscript. These co-authors all had a role in each aspect of in the study design, decision to publish, and preparation of the manuscript

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