The role of growth factors in maintenance of stemness in bone marrow-derived mesenchymal stem cells

Young Woo Eom, Ji Eun Oh, Jong In Lee, Soonkoo Baik, Kijong Rhee, Ha Cheol Shin, Yong Man Kim, Chan Mug Ahn, Jee Hyun Kong, Hyun Soo Kim, Kwang Yong Shim

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Mesenchymal stem cells (MSCs) are an active topic of research in regenerative medicine due to their ability to secrete a variety of growth factors and cytokines that promote healing of damaged tissues and organs. In addition, these secreted growth factors and cytokines have been shown to exert an autocrine effect by regulating MSC proliferation and differentiation. We found that expression of EGF, FGF-4 and HGF were down-regulated during serial passage of bone marrow-derived mesenchymal stem cells (BMSCs). Proliferation and differentiation potentials of BMSCs treated with these growth factors for 2 months were evaluated and compared to BMSCs treated with FGF-2, which increased proliferation of BMSCs. FGF-2 and -4 increased proliferation potentials at high levels, about 76- and 26-fold, respectively, for 2 months, while EGF and HGF increased proliferation of BMSCs by less than 2.8-fold. Interestingly, differentiation potential, especially adipogenesis, was maintained only by HGF treatment. Treatment with FGF-2 rapidly induced activation of AKT and later induced ERK activation. The basal level of phosphorylated ERK increased during serial passage of BMSCs treated with FGF-2. The expression of LC3-II, an autophagy marker, was gradually increased and the population of senescent cells was increased dramatically at passage 7 in non-treated controls. But FGF-2 and FGF-4 suppressed LC3-II expression and down-regulated senescent cells during long-term (i.e. 2 month) cultures. Taken together, depletion of growth factors during serial passage could induce autophagy, senescence and down-regulation of stemness (proliferation via FGF-2/-4 and differentiation via HGF) through suppression of AKT and ERK signaling.

Original languageEnglish
Pages (from-to)16-22
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume445
Issue number1
DOIs
Publication statusPublished - 2014 Feb 28

Fingerprint

Stem cells
Mesenchymal Stromal Cells
Intercellular Signaling Peptides and Proteins
Bone
Fibroblast Growth Factor 2
Bone Marrow
Maintenance
Serial Passage
Autophagy
Epidermal Growth Factor
Chemical activation
Cytokines
Adipogenesis
Regenerative Medicine
Cell proliferation
Cell Differentiation
Down-Regulation
Cells
Cell Proliferation
Tissue

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Eom, Young Woo ; Oh, Ji Eun ; Lee, Jong In ; Baik, Soonkoo ; Rhee, Kijong ; Shin, Ha Cheol ; Kim, Yong Man ; Ahn, Chan Mug ; Kong, Jee Hyun ; Kim, Hyun Soo ; Shim, Kwang Yong. / The role of growth factors in maintenance of stemness in bone marrow-derived mesenchymal stem cells. In: Biochemical and Biophysical Research Communications. 2014 ; Vol. 445, No. 1. pp. 16-22.
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The role of growth factors in maintenance of stemness in bone marrow-derived mesenchymal stem cells. / Eom, Young Woo; Oh, Ji Eun; Lee, Jong In; Baik, Soonkoo; Rhee, Kijong; Shin, Ha Cheol; Kim, Yong Man; Ahn, Chan Mug; Kong, Jee Hyun; Kim, Hyun Soo; Shim, Kwang Yong.

In: Biochemical and Biophysical Research Communications, Vol. 445, No. 1, 28.02.2014, p. 16-22.

Research output: Contribution to journalArticle

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AU - Eom, Young Woo

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AU - Rhee, Kijong

AU - Shin, Ha Cheol

AU - Kim, Yong Man

AU - Ahn, Chan Mug

AU - Kong, Jee Hyun

AU - Kim, Hyun Soo

AU - Shim, Kwang Yong

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