Abstract

This aim of our study was to evaluate a novel cell-based therapy for contusion spinal cord injury (SCI) using embryonic-derived NIH3T3 cells, which endogenously express glial cell line-derived neurotrophic factor (GDNF). Methods: Proliferation and differentiation of transplanted NIH3T3 cells and their anti-apoptotic effects were examined after their engraftment into the spinal cords of Long-Evans rats subjected to acute SCI at the T10 vertebral level by a New York University impactor device. NIH3T3 cells were initially engineered to contain dual reporter genes, namely thymidine kinase (T) and enhanced green fluorescence protein (G), for in vivo cell tracking by both nuclear and fluorescence imaging modalities. Results: Planar and fluorescence imaging demonstrated that transplanted NIH3T3-TG cells at the L1 vertebral level migrated 2 cm distal to the injury site as early as 2 h, and the signals persisted for 48 h after SCI. The expression of GDNF by NIH3T3-TG cells was then confirmed by immunohistochemical analysis both in vitro and in vivo. GDNF-secreting NIH3T3-TG transplant provided anti-apoptotic effects in the injured cord over the period of 3 wk. Finally, NIH3T3-TG cells cultured under neuronal differentiation medium exhibited both morphologic and genetic resemblance to neuronal cells. Conclusion: GDNF-secreting NIH3T3-TG cells in combination with molecular imaging could be a platform for developing therapeutic tools for acute SCI.

Original languageEnglish
Pages (from-to)1512-1519
Number of pages8
JournalJournal of Nuclear Medicine
Volume49
Issue number9
DOIs
Publication statusPublished - Sep 1 2008

Fingerprint

Glial Cell Line-Derived Neurotrophic Factor
Molecular Imaging
Contusions
Cell- and Tissue-Based Therapy
Spinal Cord Injuries
Reporter Genes
Optical Imaging
Cell Tracking
Long Evans Rats
Thymidine Kinase
Cultured Cells
Spinal Cord
Fluorescence
Transplants
Equipment and Supplies
Wounds and Injuries

Keywords

  • Animal imaging
  • GDNF
  • GFP
  • Molecular imaging
  • Neurology
  • Spinal cord injury

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

A novel cell-based therapy for contusion spinal cord injury using GDNF-delivering NIH3T3 cells with dual reporter genes monitored by molecular imaging. / Lo, Wen Cheng; Hsu, Chung Huei; Wu, Alexander T H; Yang, Liang Yo; Chen, Wei Hong; Chiu, Wen Ta; Lai, Wen-FuThomas; Wu, Chih Hsiung; Gelovani, Juri G.; Deng, Win Ping.

In: Journal of Nuclear Medicine, Vol. 49, No. 9, 01.09.2008, p. 1512-1519.

Research output: Contribution to journalArticle

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title = "A novel cell-based therapy for contusion spinal cord injury using GDNF-delivering NIH3T3 cells with dual reporter genes monitored by molecular imaging",
abstract = "This aim of our study was to evaluate a novel cell-based therapy for contusion spinal cord injury (SCI) using embryonic-derived NIH3T3 cells, which endogenously express glial cell line-derived neurotrophic factor (GDNF). Methods: Proliferation and differentiation of transplanted NIH3T3 cells and their anti-apoptotic effects were examined after their engraftment into the spinal cords of Long-Evans rats subjected to acute SCI at the T10 vertebral level by a New York University impactor device. NIH3T3 cells were initially engineered to contain dual reporter genes, namely thymidine kinase (T) and enhanced green fluorescence protein (G), for in vivo cell tracking by both nuclear and fluorescence imaging modalities. Results: Planar and fluorescence imaging demonstrated that transplanted NIH3T3-TG cells at the L1 vertebral level migrated 2 cm distal to the injury site as early as 2 h, and the signals persisted for 48 h after SCI. The expression of GDNF by NIH3T3-TG cells was then confirmed by immunohistochemical analysis both in vitro and in vivo. GDNF-secreting NIH3T3-TG transplant provided anti-apoptotic effects in the injured cord over the period of 3 wk. Finally, NIH3T3-TG cells cultured under neuronal differentiation medium exhibited both morphologic and genetic resemblance to neuronal cells. Conclusion: GDNF-secreting NIH3T3-TG cells in combination with molecular imaging could be a platform for developing therapeutic tools for acute SCI.",
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author = "Lo, {Wen Cheng} and Hsu, {Chung Huei} and Wu, {Alexander T H} and Yang, {Liang Yo} and Chen, {Wei Hong} and Chiu, {Wen Ta} and Wen-FuThomas Lai and Wu, {Chih Hsiung} and Gelovani, {Juri G.} and Deng, {Win Ping}",
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AU - Lo, Wen Cheng

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AU - Wu, Alexander T H

AU - Yang, Liang Yo

AU - Chen, Wei Hong

AU - Chiu, Wen Ta

AU - Lai, Wen-FuThomas

AU - Wu, Chih Hsiung

AU - Gelovani, Juri G.

AU - Deng, Win Ping

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