Open AccessPreclinical assessment of thrombin‐preconditioned human Wharton’s jelly‐derived mesenchymal stem cells for neonatal hypoxic‐ischaemic brain injury
Author(s) -
Noh JungHo,
Jeong JiSeong,
Park SangJin,
Jin Jung Kyung,
Lee ByoungSeok,
Kim WooJin,
Han JiSeok,
Cho MinKyung,
Sung Dong Kyung,
Ahn So Yoon,
Chang Yun Sil,
Son HwaYoung,
Jeong Eun Ju
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16971
Subject(s) - mesenchymal stem cell , medicine , pharmacology , stem cell , biodistribution , wharton's jelly , encephalopathy , pathology , in vivo , biology , microbiology and biotechnology , genetics
Abstract 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 × 10 5 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.