Therapeutic effect of bdnf-overexpressing human neural stem cells (F3.bdnf) in a contusion model of spinal cord injury in rats

Da Jeong Chang, Hwi Young Cho, Seyoung Hwang, Nayeon Lee, Chunggab Choi, Hyunseung Lee, Kwan Soo Hong, Seung Hun Oh, Hyun Sook Kim, Dong Ah Shin, Young Wook Yoon, Jihwan Song

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Abstract

The most common type of spinal cord injury is the contusion of the spinal cord, which causes progressive secondary tissue degeneration. In this study, we applied genetically modified human neural stem cells overexpressing BDNF (brain-derived neurotrophic factor) (F3.BDNF) to determine whether they can promote functional recovery in the spinal cord injury (SCI) model in rats. We transplanted F3.BDNF cells via intrathecal catheter delivery after a contusion of the tho-racic spinal cord and found that they were migrated toward the injured spinal cord area by MR imaging. Transplanted F3.BDNF cells expressed neural lineage markers, such as NeuN, MBP, and GFAP and were functionally connected to the host neurons. The F3.BDNF-transplanted rats exhib-ited significantly improved locomotor functions compared with the sham group. This functional recovery was accompanied by an increased volume of spared myelination and decreased area of cystic cavity in the F3.BDNF group. We also observed that the F3.BDNF-transplanted rats showed reduced numbers of Iba1-and iNOS-positive inflammatory cells as well as GFAP-positive astro-cytes. These results strongly suggest the transplantation of F3.BDNF cells can modulate inflammatory cells and glia activation and also improve the hyperalgesia following SCI.

Original languageEnglish
Article number6970
JournalInternational journal of molecular sciences
Volume22
Issue number13
DOIs
Publication statusPublished - 2021 Jul 1

Bibliographical note

Funding Information:
Funding: This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (A111016) and the internal funding from iPS Bio, Inc.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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