Subcutaneous transplantation of human thyroid tissue into a pre-vascularized Cell Pouch™ device in a Mus musculus model: Evidence of viability and function for thyroid transplantation

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.

Vascularization in Bioartificial Parenchymal Tissue: Bioink and Bioprinting Strategies

“…In addition to preprinting processes that focus, for example, on the integration of angiogenic cues in bioink formulations, there are also adjuvant postprinting strategies to promote vascularization. Several studies have proposed a two-stage approach enabling sufficient prevascularization prior to effector cell loading [ 15 , 69 , 125 , 126 , 127 , 128 , 129 ]. Prevascularization can be induced by in vivo implantation of a foreign body in the weeks leading up to implantation of the effector-cell-containing bioprinted construct.…”

“…Local inflammatory and immune reactions cause enhanced angiogenesis [ 15 ]. CellPouch TM is an implantable and retrievable device for transplantation and long-term housing of effector cells and tissue [ 128 , 129 ]. The device is implanted subcutaneously several weeks prior to effector cell loading into the device [ 128 , 129 ].…”

“…CellPouch TM is an implantable and retrievable device for transplantation and long-term housing of effector cells and tissue [ 128 , 129 ]. The device is implanted subcutaneously several weeks prior to effector cell loading into the device [ 128 , 129 ]. The prevascularized housing enabled successful grafting of thyroid tissue and pancreatic islets in vivo [ 128 , 129 ].…”

“…The device is implanted subcutaneously several weeks prior to effector cell loading into the device [ 128 , 129 ]. The prevascularized housing enabled successful grafting of thyroid tissue and pancreatic islets in vivo [ 128 , 129 ]. Transient implantation of a foreign body before effector cell implantation can avoid autoimmunity and foreign body response while maintaining angiogenic effects [ 130 ].…”

Human Leukocyte Antigens

“…Approximately eight in vivo studies exist between 1981 and 2022 [117][118][119][120][121][122][123]. In these studies on thyroid transplantation; auto-and allotransplantation of irradiated thyroid tissue in rats with syngenic rats have been evaluated.…”