Bio-distribution and toxicity potential of human umbilical cord mesenchymal stem cells in cynomolgus monkeys.
Sci Rep
; 14(1): 12251, 2024 05 28.
Article
em En
| MEDLINE
| ID: mdl-38806615
ABSTRACT
Mesenchymal stem cells (MSCs) have demonstrated promising advantages in the therapies of many diseases, while its multi-directional differentiation potential and immunotoxicity are the major concerns hindered their clinical translation. In this study, human umbilical Mesenchymal stem cell (hUC-MSCs) were labeled with a near-infrared fluorescent dye DiR before infused into cynomolgus monkeys, and the amount of hUC-MSCs in the peripheral blood were dynamically estimated from 5 min to 28 days post a single administration at 3 × 106 cells/kg and 2 × 107 cells/kg intravenously. As results, some hUC-MSCs distributed to the whole body within 5 min, while most of the cells accumulate in the lungs along with the systemic blood circulation, and subsequently released into the blood. The toxicity potentials of hUC-MSCs were investigated in another 30 cynomolgus monkeys, and the cells were repeatedly administrated at doses of 3 × 106 cells/kg and 2 × 107 cells/kg for 5 times on a weekly basis, with a recovery period of 1 months. hUC-MSCs showed no obvious toxic effects in cynomolgus monkeys, except xenogeneic immune rejection to human stem cells. Low levels of the hUC-MSC gene were detected in the peripheral blood of a few animals administered 2 × 107 cells/kg at 30 min subsequent to the first and last administration, and there was no significant difference in the copy number of the hUC-MSC gene in the blood samples compared with the first and last administration, indicating that the hUC-MSC was not significantly amplified in vivo, and it its safe in non-human primates. Our study for the first time verified the safety of long-term use of hUC-MSCs in primates. We have pioneered a technology for the real-time detection of hUC-MSCs in peripheral blood and provide dynamicand rapid monitoring of the distribution characteristics of hUC-MSCs in vivo. Here, we provide data supporting the application of such products for clinical treatment and the application of stem cells in major refractory diseases and regenerative medicine.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cordão Umbilical
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Transplante de Células-Tronco Mesenquimais
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Células-Tronco Mesenquimais
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Macaca fascicularis
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
Reino Unido