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

doi:10.3390/ijms22136970

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

Department of Neurosurgery

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

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 language	English
Article number	6970
Journal	International journal of molecular sciences
Volume	22
Issue number	13
DOIs	https://doi.org/10.3390/ijms22136970
Publication status	Published - 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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Chang, D. J., Cho, H. Y., Hwang, S., Lee, N., Choi, C., Lee, H., Hong, K. S., Oh, S. H., Kim, H. S., Shin, D. A., Yoon, Y. W., & Song, J. (2021). Therapeutic effect of bdnf-overexpressing human neural stem cells (F3.bdnf) in a contusion model of spinal cord injury in rats. International journal of molecular sciences, 22(13), Article 6970. https://doi.org/10.3390/ijms22136970

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

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.",

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

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: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Oh, Seung Hun

AU - Kim, Hyun Sook

AU - Shin, Dong Ah

AU - Yoon, Young Wook

AU - Song, Jihwan

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AB - 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.

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

Abstract

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