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Intracerebroventricular Administration of Human Umbilical Cord Blood—Derived Mesenchymal Stem Cells Induces Transient Inflammation in a Transgenic Mouse Model and Patients with Alzheimer’s Disease
Previously we conducted a Phase I/IIa clinical trial in nine patients with mild to moderate Alzheimer’s disease (AD). Unexpectedly, all patients who were given injections of human-umbilical cord-blood-derived mesenchymal stem cells (hUCB-MSCs) developed fever which subsided after 24 h. Several possi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945031/ https://www.ncbi.nlm.nih.gov/pubmed/35327365 http://dx.doi.org/10.3390/biomedicines10030563 |
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author | Myeong, Su Hyeon Kim, Hyeongseop Lee, Na Kyung Hwang, Jung Won Kim, Hee Jin Jang, Hyemin Choi, Soo Jin Na, Duk L. |
author_facet | Myeong, Su Hyeon Kim, Hyeongseop Lee, Na Kyung Hwang, Jung Won Kim, Hee Jin Jang, Hyemin Choi, Soo Jin Na, Duk L. |
author_sort | Myeong, Su Hyeon |
collection | PubMed |
description | Previously we conducted a Phase I/IIa clinical trial in nine patients with mild to moderate Alzheimer’s disease (AD). Unexpectedly, all patients who were given injections of human-umbilical cord-blood-derived mesenchymal stem cells (hUCB-MSCs) developed fever which subsided after 24 h. Several possible causes of transient fever include bacterial infection, inflammatory reaction from the cell culture media composition, or the cells themselves. To delineate these causes, first we compared the levels of several cytokines in the cerebrospinal fluid (CSF) of AD patients who received saline (placebo) or hUCB-MSC injections, respectively. Compared to the placebo group, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and c-reactive protein (CRP) levels were increased in the hUCB-MSC group. Negative bacterial culture results of the CSF samples and the fact that the same hUCB-MSC administration procedure was used for both the placebo and hUCB-MSC groups ruled out the bacterial infection hypothesis. However, it was not yet clear as to whether the transplanted cells or the composition of the cell culture media generated the transient fever. Therefore, we carried out intracerebroventricular (ICV) injections of hUCB-MSCs in a 5xFAD mouse model of AD. Interestingly, we discovered that pro-inflammatory cytokine levels were higher in the hUCB-MSC group. Taken together, our data suggest that the cause of transient inflammatory response observed from both the clinical trial and mouse study was due to the transplanted hUCB-MSCs. |
format | Online Article Text |
id | pubmed-8945031 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89450312022-03-25 Intracerebroventricular Administration of Human Umbilical Cord Blood—Derived Mesenchymal Stem Cells Induces Transient Inflammation in a Transgenic Mouse Model and Patients with Alzheimer’s Disease Myeong, Su Hyeon Kim, Hyeongseop Lee, Na Kyung Hwang, Jung Won Kim, Hee Jin Jang, Hyemin Choi, Soo Jin Na, Duk L. Biomedicines Article Previously we conducted a Phase I/IIa clinical trial in nine patients with mild to moderate Alzheimer’s disease (AD). Unexpectedly, all patients who were given injections of human-umbilical cord-blood-derived mesenchymal stem cells (hUCB-MSCs) developed fever which subsided after 24 h. Several possible causes of transient fever include bacterial infection, inflammatory reaction from the cell culture media composition, or the cells themselves. To delineate these causes, first we compared the levels of several cytokines in the cerebrospinal fluid (CSF) of AD patients who received saline (placebo) or hUCB-MSC injections, respectively. Compared to the placebo group, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and c-reactive protein (CRP) levels were increased in the hUCB-MSC group. Negative bacterial culture results of the CSF samples and the fact that the same hUCB-MSC administration procedure was used for both the placebo and hUCB-MSC groups ruled out the bacterial infection hypothesis. However, it was not yet clear as to whether the transplanted cells or the composition of the cell culture media generated the transient fever. Therefore, we carried out intracerebroventricular (ICV) injections of hUCB-MSCs in a 5xFAD mouse model of AD. Interestingly, we discovered that pro-inflammatory cytokine levels were higher in the hUCB-MSC group. Taken together, our data suggest that the cause of transient inflammatory response observed from both the clinical trial and mouse study was due to the transplanted hUCB-MSCs. MDPI 2022-02-28 /pmc/articles/PMC8945031/ /pubmed/35327365 http://dx.doi.org/10.3390/biomedicines10030563 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Myeong, Su Hyeon Kim, Hyeongseop Lee, Na Kyung Hwang, Jung Won Kim, Hee Jin Jang, Hyemin Choi, Soo Jin Na, Duk L. Intracerebroventricular Administration of Human Umbilical Cord Blood—Derived Mesenchymal Stem Cells Induces Transient Inflammation in a Transgenic Mouse Model and Patients with Alzheimer’s Disease |
title | Intracerebroventricular Administration of Human Umbilical Cord Blood—Derived Mesenchymal Stem Cells Induces Transient Inflammation in a Transgenic Mouse Model and Patients with Alzheimer’s Disease |
title_full | Intracerebroventricular Administration of Human Umbilical Cord Blood—Derived Mesenchymal Stem Cells Induces Transient Inflammation in a Transgenic Mouse Model and Patients with Alzheimer’s Disease |
title_fullStr | Intracerebroventricular Administration of Human Umbilical Cord Blood—Derived Mesenchymal Stem Cells Induces Transient Inflammation in a Transgenic Mouse Model and Patients with Alzheimer’s Disease |
title_full_unstemmed | Intracerebroventricular Administration of Human Umbilical Cord Blood—Derived Mesenchymal Stem Cells Induces Transient Inflammation in a Transgenic Mouse Model and Patients with Alzheimer’s Disease |
title_short | Intracerebroventricular Administration of Human Umbilical Cord Blood—Derived Mesenchymal Stem Cells Induces Transient Inflammation in a Transgenic Mouse Model and Patients with Alzheimer’s Disease |
title_sort | intracerebroventricular administration of human umbilical cord blood—derived mesenchymal stem cells induces transient inflammation in a transgenic mouse model and patients with alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945031/ https://www.ncbi.nlm.nih.gov/pubmed/35327365 http://dx.doi.org/10.3390/biomedicines10030563 |
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