Immunosuppressed Miniswine as a Model for Testing Cell Therapy Success: Experience With Implants of Human Salivary Stem/Progenitor Cell Constructs

Simple item page
dc.citation.articleNumber711602en_US
dc.citation.journalTitleFrontiers in Molecular Biosciencesen_US
dc.citation.volumeNumber8en_US
dc.contributor.authorWu, Danielleen_US
dc.contributor.authorLombaert, Isabelle M. A.en_US
dc.contributor.authorDeLeon, Maximilienen_US
dc.contributor.authorPradhan-Bhatt, Swatien_US
dc.contributor.authorWitt, Robert Len_US
dc.contributor.authorHarrington, Daniel Antonen_US
dc.contributor.authorTrombetta, Mark Gen_US
dc.contributor.authorPassineau, Michael Jen_US
dc.contributor.authorFarach-Carson, Mary C.en_US
dc.date.accessioned2021-10-28T18:47:23Zen_US
dc.date.available2021-10-28T18:47:23Zen_US
dc.date.issued2021en_US
dc.description.abstractAn urgent need exists to develop large animal models for preclinical testing of new cell therapies designed to replace lost or damaged tissues. Patients receiving irradiation for treatment of head and neck cancers frequently develop xerostomia/dry mouth, a condition that could one day be treated by cell therapy to repopulate functional saliva-producing cells. Using immunosuppression protocols developed for patients receiving whole face transplants, we successfully used immunosuppressed miniswine as a suitable host animal to evaluate the long-term stability, biocompatibility, and fate of matrix-modified hyaluronate (HA) hydrogel/bioscaffold materials containing encapsulated salivary human stem/progenitor cells (hS/PCs). An initial biocompatibility test was conducted in parotids of untreated miniswine. Subsequent experiments using hS/PC-laden hydrogels were performed in animals, beginning an immunosuppression regimen on the day of surgery. Implant sites included the kidney capsule for viability testing and the parotid gland for biointegration time periods up to eight weeks. No transplant rejection was seen in any animal assessed by analysis of the tissues near the site of the implants. First-generation implants containing only cells in hydrogel proved difficult to handle in the surgical suite and were modified to adhere to a porcine small intestinal submucosa (SIS) membrane for improved handling and could be delivered through the da Vinci surgical system. Several different surgical techniques were assessed using the second-generation 3D-salivary tissue (3D-ST) for ease and stability both on the kidney capsule and in the capsule-less parotid gland. For the kidney, sliding the implant under the capsule membrane and quick stitching proved superior to other methods. For the parotid gland, creation of a tissue “pocket” for placement and immediate multilayer tissue closure were well tolerated with minimal tissue damage. Surgical clips were placed as fiduciary markers for tissue harvest. Some implant experiments were conducted with miniswine 90 days post-irradiation when salivation decreased significantly. Sufficient parotid tissue remained to allow implant placement, and animals tolerated immunosuppression. In all experiments, viability of implanted hS/PCs was high with clear signs of both vascular and nervous system integration in the parotid implants. We thus conclude that the immunosuppressed miniswine is a high-value emerging model for testing human implants prior to first-in-human trials.en_US
dc.identifier.citationWu, Danielle, Lombaert, Isabelle M. A., DeLeon, Maximilien, et al.. "Immunosuppressed Miniswine as a Model for Testing Cell Therapy Success: Experience With Implants of Human Salivary Stem/Progenitor Cell Constructs." <i>Frontiers in Molecular Biosciences,</i> 8, (2021) Frontiers Media S.A.: https://doi.org/10.3389/fmolb.2021.711602.en_US
dc.identifier.digitalfmolb-08-711602en_US
dc.identifier.doihttps://doi.org/10.3389/fmolb.2021.711602en_US
dc.identifier.urihttps://hdl.handle.net/1911/111618en_US
dc.language.isoengen_US
dc.publisherFrontiers Media S.A.en_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleImmunosuppressed Miniswine as a Model for Testing Cell Therapy Success: Experience With Implants of Human Salivary Stem/Progenitor Cell Constructsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
fmolb-08-711602.pdf
Size:
4.91 MB
Format:
Adobe Portable Document Format
Download
Collections
Faculty Publications
Bioengineering Publications
BioSciences Publications