Journal of cellular and molecular medicine, 2021-11, Vol.25 (22), p.10430-10440
2021
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- Autor(en) / Beteiligte
- Titel
- Preclinical assessment of thrombin‐preconditioned human Wharton’s jelly‐derived mesenchymal stem cells for neonatal hypoxic‐ischaemic brain injury
- Ist Teil von
- Journal of cellular and molecular medicine, 2021-11, Vol.25 (22), p.10430-10440
- Ort / Verlag
- England: John Wiley & Sons, Inc
- Erscheinungsjahr
- 2021
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Hypoxic‐ischaemic encephalopathy (HIE) is a type of brain injury affecting approximately 1 million newborn babies per year worldwide, the only treatment for which is therapeutic hypothermia. Thrombin‐preconditioned mesenchymal stem cells (MSCs) exert neuroprotective effects by enriching cargo contents and boosting exosome biogenesis, thus showing promise as a new therapeutic strategy for HIE. This study was conducted to evaluate the tissue distribution and potential toxicity of thrombin‐preconditioned human Wharton's jelly‐derived mesenchymal stem cells (th‐hWJMSCs) in animal models before the initiation of clinical trials. We investigated the biodistribution, tumorigenicity and general toxicity of th‐hWJMSCs. MSCs were administered the maximum feasible dose (1 × 105 cells/10 µL/head) once, or at lower doses into the cerebral ventricle. To support the clinical use of th‐hWJMSCs for treating brain injury, preclinical safety studies were conducted in newborn Sprague‐Dawley rats and BALB/c nude mice. In addition, growth parameters were evaluated to assess the impact of th‐hWJMSCs on the growth of newborn babies. Our results suggest that th‐hWJMSCs are non‐toxic and non‐tumorigenic in rodent models, survive for up to 7 days in the brain and hold potential for HIE therapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1582-1838eISSN: 1582-4934DOI: 10.1111/jcmm.16971Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8581315
- Format
- –
- Schlagworte
- Animal models, Animals, Animals, Newborn, Biodistribution, Biomarkers, Brain damage, Brain diseases, Brain injury, Cell culture, Cell Transformation, Neoplastic, Clinical trials, disease, Disease Management, Disease Models, Animal, Drug dosages, Encephalopathy, FDA approval, Growth factors, Humans, Hypothermia, Hypoxia, Hypoxia-Ischemia, Brain - etiology, Hypoxia-Ischemia, Brain - metabolism, Hypoxia-Ischemia, Brain - therapy, hypoxic‐ischaemic encephalopathy, Ischemia, Laboratory animals, Manufacturing, Medical research, mesenchymal stem cell transplantation, Mesenchymal Stem Cell Transplantation - adverse effects, Mesenchymal Stem Cell Transplantation - methods, Mesenchymal stem cells, Mesenchymal Stem Cells - cytology, Mesenchymal Stem Cells - drug effects, Mesenchymal Stem Cells - metabolism, Mice, Neonates, Neuroprotection, newborn, Original, Rats, Rodents, Stem cell transplantation, Stem cells, Thrombin, Thrombin - metabolism, Thrombin - pharmacology, Toxicity, toxicology, Tumorigenicity, Ventricle, Ventricles (cerebral), Wharton Jelly - cytology