Adipose tissue-derived mesenchymal stem cells cultured at high cell density express brain-derived neurotrophic factor and exert neuroprotective effects in a 6-hydroxydopamine rat model of Parkinson’s disease

Joon Beom Park, Jin Suk Lee, Byung Pil Cho, Kijong Rhee, Soonkoo Baik, Jiye Kim, Seong Joon Kang, Dong Joon Park, Ji Eun Oh, Ha Cheol Shin, Yong Man Kim, Hyun Soo Kim, Keumseok Bae, Young Woo Eom

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Abstract

Mesenchymal stem cells (MSCs) secrete neurotrophic factors, and have been reported to improve functional outcomes in animal models of neurodegenerative diseases such as cerebral ischemia, stroke, spinal cord lesions, and Parkinson’s disease. Previously, we found that adipose tissue-derived mesenchymal stem cells (ASCs) cultured at high cell density (HD-ASCs) expressed interferon-beta (IFN-β). Here we demonstrate that ASCs expressing IFN-β also express brain-derived neurotrophic factor (BDNF). Growth rates of neuroblastoma cells (SK-N-BE(2)C) were increased when co-cultured with HD-ASCs or treated with concentrated medium obtained from HD-ASCs (HD-ASC-CM). The HD-ASC-CM induced AKT phosphorylation in SK-N-BE(2)C cells, and AKT inhibition by Ly294002 reduced cell viability of SK-N-BE(2)C cells. Additionally, a protective effect on SK-N-BE(2)C cells exposed to 6-hydroxydopamine (6-OHDA) was observed in the HD-ASC-CM or brain-derived neurotrophic factor (BDNF) treated cells. The protective effect of the HD-ASC-CM was neutralized by anti-BDNF antibody. In the 6-OHDA-induced Parkinson’s disease rat model, ASCs reduced amphetamine-induced rotations and a greater number of tyrosine hydroxylase (TH)-positive cells were observed in the HD-ASCs-injected group compared with sham controls and the low density cultured ASC-injected group. Moreover, the expression of BDNF, nerve growth factor (NGF), TH, and proliferating cell nuclear antigen (PCNA) in ipsilateral midbrain tissues including substantia nigra pars compacta (SNc) was increased by transplantation of HD-ASCs. These data indicate that HD-ASCs may induce neuroprotective effects through BDNF expression and subsequent increase of proliferation in neuronal cells both in vitro and in vivo.

Original languageEnglish
Pages (from-to)213-221
Number of pages9
JournalGenes and Genomics
Volume37
Issue number2
DOIs
Publication statusPublished - 2014 Jan 1

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Oxidopamine
Brain-Derived Neurotrophic Factor
Neuroprotective Agents
Stem cells
Mesenchymal Stromal Cells
Parkinson Disease
Adipose Tissue
Rats
Cell Count
Tissue
Interferon-beta
Cells
Tyrosine 3-Monooxygenase
Neurodegenerative diseases
Phosphorylation
Nerve Growth Factors
Proliferating Cell Nuclear Antigen
Nerve Growth Factor
Amphetamine
Spinal Cord Diseases

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Park, Joon Beom ; Lee, Jin Suk ; Cho, Byung Pil ; Rhee, Kijong ; Baik, Soonkoo ; Kim, Jiye ; Kang, Seong Joon ; Park, Dong Joon ; Oh, Ji Eun ; Shin, Ha Cheol ; Kim, Yong Man ; Kim, Hyun Soo ; Bae, Keumseok ; Eom, Young Woo. / Adipose tissue-derived mesenchymal stem cells cultured at high cell density express brain-derived neurotrophic factor and exert neuroprotective effects in a 6-hydroxydopamine rat model of Parkinson’s disease. In: Genes and Genomics. 2014 ; Vol. 37, No. 2. pp. 213-221.
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abstract = "Mesenchymal stem cells (MSCs) secrete neurotrophic factors, and have been reported to improve functional outcomes in animal models of neurodegenerative diseases such as cerebral ischemia, stroke, spinal cord lesions, and Parkinson’s disease. Previously, we found that adipose tissue-derived mesenchymal stem cells (ASCs) cultured at high cell density (HD-ASCs) expressed interferon-beta (IFN-β). Here we demonstrate that ASCs expressing IFN-β also express brain-derived neurotrophic factor (BDNF). Growth rates of neuroblastoma cells (SK-N-BE(2)C) were increased when co-cultured with HD-ASCs or treated with concentrated medium obtained from HD-ASCs (HD-ASC-CM). The HD-ASC-CM induced AKT phosphorylation in SK-N-BE(2)C cells, and AKT inhibition by Ly294002 reduced cell viability of SK-N-BE(2)C cells. Additionally, a protective effect on SK-N-BE(2)C cells exposed to 6-hydroxydopamine (6-OHDA) was observed in the HD-ASC-CM or brain-derived neurotrophic factor (BDNF) treated cells. The protective effect of the HD-ASC-CM was neutralized by anti-BDNF antibody. In the 6-OHDA-induced Parkinson’s disease rat model, ASCs reduced amphetamine-induced rotations and a greater number of tyrosine hydroxylase (TH)-positive cells were observed in the HD-ASCs-injected group compared with sham controls and the low density cultured ASC-injected group. Moreover, the expression of BDNF, nerve growth factor (NGF), TH, and proliferating cell nuclear antigen (PCNA) in ipsilateral midbrain tissues including substantia nigra pars compacta (SNc) was increased by transplantation of HD-ASCs. These data indicate that HD-ASCs may induce neuroprotective effects through BDNF expression and subsequent increase of proliferation in neuronal cells both in vitro and in vivo.",
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Adipose tissue-derived mesenchymal stem cells cultured at high cell density express brain-derived neurotrophic factor and exert neuroprotective effects in a 6-hydroxydopamine rat model of Parkinson’s disease. / Park, Joon Beom; Lee, Jin Suk; Cho, Byung Pil; Rhee, Kijong; Baik, Soonkoo; Kim, Jiye; Kang, Seong Joon; Park, Dong Joon; Oh, Ji Eun; Shin, Ha Cheol; Kim, Yong Man; Kim, Hyun Soo; Bae, Keumseok; Eom, Young Woo.

In: Genes and Genomics, Vol. 37, No. 2, 01.01.2014, p. 213-221.

Research output: Contribution to journalArticle

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AU - Park, Joon Beom

AU - Lee, Jin Suk

AU - Cho, Byung Pil

AU - Rhee, Kijong

AU - Baik, Soonkoo

AU - Kim, Jiye

AU - Kang, Seong Joon

AU - Park, Dong Joon

AU - Oh, Ji Eun

AU - Shin, Ha Cheol

AU - Kim, Yong Man

AU - Kim, Hyun Soo

AU - Bae, Keumseok

AU - Eom, Young Woo

PY - 2014/1/1

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