Transplantation of Human Peripheral Stem and Progenitor Cells to Humanized Mouse Model for Systemic Lupus Erythematosus
Syahrul Chilmi, Dina Fauziah, Matthew Brian Khrisna, Ifa Fauziah, Friska Supriyanto, Kusworini Handono, Kevin Reinaldo Sunjaya, Wimardy Leonard Wijaya, Mustofa Aidid, Hani Susianti Clinical Pathology Department, Faculty of Medicine Brawijaya University/Dr. Saiful Anwar General Hospital, Malang, Indo...
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Dove Medical Press
2025-06-01
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| author | Chilmi S Fauziah D Khrisna MB Fauziah I Supriyanto F Handono K Sunjaya KR Wijaya WL Aidid M Susianti H |
| author_facet | Chilmi S Fauziah D Khrisna MB Fauziah I Supriyanto F Handono K Sunjaya KR Wijaya WL Aidid M Susianti H |
| author_sort | Chilmi S |
| collection | DOAJ |
| description | Syahrul Chilmi, Dina Fauziah, Matthew Brian Khrisna, Ifa Fauziah, Friska Supriyanto, Kusworini Handono, Kevin Reinaldo Sunjaya, Wimardy Leonard Wijaya, Mustofa Aidid, Hani Susianti Clinical Pathology Department, Faculty of Medicine Brawijaya University/Dr. Saiful Anwar General Hospital, Malang, IndonesiaCorrespondence: Hani Susianti, Clinical Pathology Department, Faculty of Medicine Brawijaya University/Dr. Saiful Anwar General Hospital, Jaksa Agung Suprapto Street Number 2, Malang, East Java, 65111, Indonesia, Tel +6281334760295, Email hanisusianti.fk@ub.ac.idIntroduction: Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by damaged and dysregulated immune system due to breakdown in the selection process during clonal growth of immune cells. Studies have shown that patients with systemic lupus erythematosus (SLE) display altered gene expression patterns and increased double-stranded DNA breaks within their hematopoietic stem and progenitor cells (HSPC). However, the current animal models for SLE found in the existing literature predominantly emphasize the use of peripheral blood mononuclear cells (PBMC) over HSPC for the creation of humanized mouse models. Nevertheless, these prior models were constrained by the limited efficiency of human cell engraftment and limited PBMC ability to replicate the capacity of HSPC to generate human SLE cells that can engraft host mice, thus making the transplant protocol inadequate.Patients and Methods: Transplantation was initiated by extracting HSPC from stable SLE patients by leukapheresis. The collected cells were assessed for purity before storage at − 80 °C. Humanized mice were conditioned with cyclophosphamide and total-body irradiation before receiving the HSPC transplant. After transplantation, the mice were administered human granulocyte-colony stimulating factor and sacrificed to evaluate autoantibodies and HSPC in their bone marrow and blood samples. Statistical analysis was performed using Student’s t-test and one-way ANOVA.Results: Upon human stem cells engravement into mice, we found a noteworthy presence of HSPC, as evidenced by the positive expression of hCD45, hCD34, and/or hCD44, and the production of human antinuclear antibodies. The results indicated that the transplanted mice generated reactive autoantibodies against human cells, similar to that observed in the human donor patient. These findings shed light on the survival and behavior of transplanted human stem cells in a mouse model.Conclusion: In this study, we successfully induced immunodeficiency in mice for xenotransplantation with human peripheral stem cells.Keywords: autoimmune, experimental, humanized mouse, stem cells |
| format | Article |
| id | doaj-art-8f5e2bd3b33f430e8970cca9533fe1b6 |
| institution | Kabale University |
| issn | 1179-2736 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Dove Medical Press |
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| series | Journal of Blood Medicine |
| spelling | doaj-art-8f5e2bd3b33f430e8970cca9533fe1b62025-08-20T03:27:00ZengDove Medical PressJournal of Blood Medicine1179-27362025-06-01Volume 16Issue 1269277103569Transplantation of Human Peripheral Stem and Progenitor Cells to Humanized Mouse Model for Systemic Lupus ErythematosusChilmi S0Fauziah D1Khrisna MB2Fauziah I3Supriyanto F4Handono K5Sunjaya KR6Wijaya WL7Aidid M8Susianti H9Clinical Pathology and Laboratory MedicineClinical pathologyClinical Pathology DepartmentClinical Pathology DepartmentClinical Pathology DepartmentDepartment of Clinical Pathology, Faculty of MedicineClinical Pathology DepartmentClinical Pathology DepartmentClinical Pathology DepartmentClinical Pathology DepartmentSyahrul Chilmi, Dina Fauziah, Matthew Brian Khrisna, Ifa Fauziah, Friska Supriyanto, Kusworini Handono, Kevin Reinaldo Sunjaya, Wimardy Leonard Wijaya, Mustofa Aidid, Hani Susianti Clinical Pathology Department, Faculty of Medicine Brawijaya University/Dr. Saiful Anwar General Hospital, Malang, IndonesiaCorrespondence: Hani Susianti, Clinical Pathology Department, Faculty of Medicine Brawijaya University/Dr. Saiful Anwar General Hospital, Jaksa Agung Suprapto Street Number 2, Malang, East Java, 65111, Indonesia, Tel +6281334760295, Email hanisusianti.fk@ub.ac.idIntroduction: Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by damaged and dysregulated immune system due to breakdown in the selection process during clonal growth of immune cells. Studies have shown that patients with systemic lupus erythematosus (SLE) display altered gene expression patterns and increased double-stranded DNA breaks within their hematopoietic stem and progenitor cells (HSPC). However, the current animal models for SLE found in the existing literature predominantly emphasize the use of peripheral blood mononuclear cells (PBMC) over HSPC for the creation of humanized mouse models. Nevertheless, these prior models were constrained by the limited efficiency of human cell engraftment and limited PBMC ability to replicate the capacity of HSPC to generate human SLE cells that can engraft host mice, thus making the transplant protocol inadequate.Patients and Methods: Transplantation was initiated by extracting HSPC from stable SLE patients by leukapheresis. The collected cells were assessed for purity before storage at − 80 °C. Humanized mice were conditioned with cyclophosphamide and total-body irradiation before receiving the HSPC transplant. After transplantation, the mice were administered human granulocyte-colony stimulating factor and sacrificed to evaluate autoantibodies and HSPC in their bone marrow and blood samples. Statistical analysis was performed using Student’s t-test and one-way ANOVA.Results: Upon human stem cells engravement into mice, we found a noteworthy presence of HSPC, as evidenced by the positive expression of hCD45, hCD34, and/or hCD44, and the production of human antinuclear antibodies. The results indicated that the transplanted mice generated reactive autoantibodies against human cells, similar to that observed in the human donor patient. These findings shed light on the survival and behavior of transplanted human stem cells in a mouse model.Conclusion: In this study, we successfully induced immunodeficiency in mice for xenotransplantation with human peripheral stem cells.Keywords: autoimmune, experimental, humanized mouse, stem cellshttps://www.dovepress.com/transplantation-of-human-peripheral-stem-and-progenitor-cells-to-human-peer-reviewed-fulltext-article-JBMAutoimmuneExperimentalHumanized MouseStem cells |
| spellingShingle | Chilmi S Fauziah D Khrisna MB Fauziah I Supriyanto F Handono K Sunjaya KR Wijaya WL Aidid M Susianti H Transplantation of Human Peripheral Stem and Progenitor Cells to Humanized Mouse Model for Systemic Lupus Erythematosus Journal of Blood Medicine Autoimmune Experimental Humanized Mouse Stem cells |
| title | Transplantation of Human Peripheral Stem and Progenitor Cells to Humanized Mouse Model for Systemic Lupus Erythematosus |
| title_full | Transplantation of Human Peripheral Stem and Progenitor Cells to Humanized Mouse Model for Systemic Lupus Erythematosus |
| title_fullStr | Transplantation of Human Peripheral Stem and Progenitor Cells to Humanized Mouse Model for Systemic Lupus Erythematosus |
| title_full_unstemmed | Transplantation of Human Peripheral Stem and Progenitor Cells to Humanized Mouse Model for Systemic Lupus Erythematosus |
| title_short | Transplantation of Human Peripheral Stem and Progenitor Cells to Humanized Mouse Model for Systemic Lupus Erythematosus |
| title_sort | transplantation of human peripheral stem and progenitor cells to humanized mouse model for systemic lupus erythematosus |
| topic | Autoimmune Experimental Humanized Mouse Stem cells |
| url | https://www.dovepress.com/transplantation-of-human-peripheral-stem-and-progenitor-cells-to-human-peer-reviewed-fulltext-article-JBM |
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