Open AccessPre-clinical study of human umbilical cord mesenchymal stem cell transplantation for the treatment of traumatic brain injury: safety evaluation from immunogenic and oncogenic perspectives
Author(s) -
Gang Wang,
Hualing Wu,
Yueping Liu,
Yan Ding,
Zilin Yuan,
Li Chen,
Qian Yang,
Yusong Gao,
Bo Diao
Publication year - 2022
Publication title -
neural regeneration research/neural regeneration research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.93
H-Index - 38
eISSN - 1876-7958
pISSN - 1673-5374
DOI - 10.4103/1673-5374.317985
Subject(s) - mesenchymal stem cell , medicine , transplantation , umbilical cord , traumatic brain injury , proinflammatory cytokine , stem cell , surgery , immunology , pathology , inflammation , biology , psychiatry , genetics
Stem cell therapy is a promising strategy for the treatment of traumatic brain injury (TBI). However, animal experiments are needed to evaluate safety; in particular, to examine the immunogenicity and tumorigenicity of human umbilical cord mesenchymal stem cells (huMSCs) before clinical application. In this study, huMSCs were harvested from human amniotic membrane and umbilical cord vascular tissue. A rat model of TBI was established using the controlled cortical impact method. Starting from the third day after injury, the rats were injected with 10 μL of 5 × 10 6 /mL huMSCs by cerebral stereotaxis or with 500 μL of 1 × 10 6 /mL huMSCs via the tail vein for 3 successive days. huMSC transplantation decreased the serum levels of proinflammatory cytokines in rats with TBI and increased the serum levels of anti-inflammatory cytokines, thereby exhibiting good immunoregulatory function. The transplanted huMSCs were distributed in the liver, lung and brain injury sites. No abnormal proliferation or tumorigenesis was found in these organs up to 12 months after transplantation. The transplanted huMSCs negligibly proliferated in vivo, and apoptosis was gradually observed at later stages. These findings suggest that huMSC transplantation for the treatment of traumatic brain injury displays good safety. In addition, huMSCs exhibit good immunoregulatory function, which can help prevent and reduce secondary brain injury caused by the rapid release of inflammatory factors after TBI. This study was approved by the Ethics Committee of Wuhan General Hospital of PLA (approval No. 20160054) on November 1, 2016.