Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged Sites
In regenerative medicine, experimental animal models are commonly used to study potential effects of human cells as therapeutic candidates. Although some studies describe certain cells, such as mesenchymal stromal cells (MSC) or human primary cells, as hypoimmunogenic and therefore unable to trigger...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | Bioengineering |
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| Online Access: | https://www.mdpi.com/2306-5354/10/9/1049 |
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| author | Thomas Später Giselle Kaneda Melissa Chavez Julia Sheyn Jacob Wechsler Victoria Yu Patricia Del Rio Dave Huang Melodie Metzger Wafa Tawackoli Dmitriy Sheyn |
| author_facet | Thomas Später Giselle Kaneda Melissa Chavez Julia Sheyn Jacob Wechsler Victoria Yu Patricia Del Rio Dave Huang Melodie Metzger Wafa Tawackoli Dmitriy Sheyn |
| author_sort | Thomas Später |
| collection | DOAJ |
| description | In regenerative medicine, experimental animal models are commonly used to study potential effects of human cells as therapeutic candidates. Although some studies describe certain cells, such as mesenchymal stromal cells (MSC) or human primary cells, as hypoimmunogenic and therefore unable to trigger strong inflammatory host responses, other studies report antibody formation and immune rejection following xenotransplantation. Accordingly, the goal of our study was to test the cellular retention and survival of human-induced pluripotent stem cell (iPSCs)-derived MSCs (iMSCs) and primary nucleus pulposus cells (NPCs) following their xenotransplantation into immune-privileged knee joints (14 days) and intervertebral discs (IVD; 7 days) of immunocompromised Nude and immunocompetent Sprague Dawley (SD) rats. At the end of both experiments, we could demonstrate that both rat types revealed comparably low levels of systemic IL-6 and IgM inflammation markers, as assessed via ELISA. Furthermore, the number of recovered cells was with no significant difference between both rat types. Conclusively, our results show that xenogeneic injection of human iMSC and NPC into immunoprivileged knee and IVD sites did not lead to an elevated inflammatory response in immunocompetent rats when compared to immunocompromised rats. Hence, immunocompetent rats represent suitable animals for xenotransplantation studies targeting immunoprivileged sites. |
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| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-10T23:01:17Z |
| publishDate | 2023-09-01 |
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| spelling | doaj.art-4a98621f986b42cf9ce09ab90d3068d02023-11-19T09:36:58ZengMDPI AGBioengineering2306-53542023-09-01109104910.3390/bioengineering10091049Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged SitesThomas Später0Giselle Kaneda1Melissa Chavez2Julia Sheyn3Jacob Wechsler4Victoria Yu5Patricia Del Rio6Dave Huang7Melodie Metzger8Wafa Tawackoli9Dmitriy Sheyn10Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAOrthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAOrthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAOrthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAOrthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAOrthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAOrthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAOrthopedics Biomechanics Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAOrthopedics Biomechanics Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAOrthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAOrthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAIn regenerative medicine, experimental animal models are commonly used to study potential effects of human cells as therapeutic candidates. Although some studies describe certain cells, such as mesenchymal stromal cells (MSC) or human primary cells, as hypoimmunogenic and therefore unable to trigger strong inflammatory host responses, other studies report antibody formation and immune rejection following xenotransplantation. Accordingly, the goal of our study was to test the cellular retention and survival of human-induced pluripotent stem cell (iPSCs)-derived MSCs (iMSCs) and primary nucleus pulposus cells (NPCs) following their xenotransplantation into immune-privileged knee joints (14 days) and intervertebral discs (IVD; 7 days) of immunocompromised Nude and immunocompetent Sprague Dawley (SD) rats. At the end of both experiments, we could demonstrate that both rat types revealed comparably low levels of systemic IL-6 and IgM inflammation markers, as assessed via ELISA. Furthermore, the number of recovered cells was with no significant difference between both rat types. Conclusively, our results show that xenogeneic injection of human iMSC and NPC into immunoprivileged knee and IVD sites did not lead to an elevated inflammatory response in immunocompetent rats when compared to immunocompromised rats. Hence, immunocompetent rats represent suitable animals for xenotransplantation studies targeting immunoprivileged sites.https://www.mdpi.com/2306-5354/10/9/1049xenotransplantationintervertebral discsmesenchymal stem cellsnucleus pulposus cellsinflammationcell therapy |
| spellingShingle | Thomas Später Giselle Kaneda Melissa Chavez Julia Sheyn Jacob Wechsler Victoria Yu Patricia Del Rio Dave Huang Melodie Metzger Wafa Tawackoli Dmitriy Sheyn Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged Sites Bioengineering xenotransplantation intervertebral discs mesenchymal stem cells nucleus pulposus cells inflammation cell therapy |
| title | Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged Sites |
| title_full | Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged Sites |
| title_fullStr | Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged Sites |
| title_full_unstemmed | Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged Sites |
| title_short | Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged Sites |
| title_sort | retention of human ipsc derived or primary cells following xenotransplantation into rat immune privileged sites |
| topic | xenotransplantation intervertebral discs mesenchymal stem cells nucleus pulposus cells inflammation cell therapy |
| url | https://www.mdpi.com/2306-5354/10/9/1049 |
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