bFGF enhances the IGFs-mediated pluripotent and differentiation potentials in multipotent stem cells

Park, Sang‐Bum; Yu, Kyung–Rok; Jung, Ji‐Won; Lee, Sae-Rom; Roh, Kyoung-Hwan; Seo, Min–Soo; Park, Jeong-Ran; Kang, Soo‐Kyung; Lee, Yong-Soon; Kang, Kyung‐Sun

doi:10.3109/08977190903289875

Cited by 22 publications

(19 citation statements)

References 39 publications

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“…Our previous studies have proven that all three types of hMSCs exhibited self-renewability and multi-lineage differentiation potential. 3, 14, 34 There were no characteristic differences among these hMSCs. The reason for the differential SOX2 expression might arise from the hMSCs source.…”

Section: Discussionmentioning

confidence: 84%

“…1 Several core ESC transcription factors are also expressed in human mesenchymal stem cells (hMSCs). 2, 3 Octamer-binding transcription factor 4 (OCT4) is a POU domain-containing transcription factor, known to be essential for the stemness and pluripotency of ESCs. 4 OCT4A has conserved roles in ESCs and in human umbilical cord blood-derived MSCs (hUCB–MSCs).…”

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confidence: 99%

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SOX2 has a crucial role in the lineage determination and proliferation of mesenchymal stem cells through Dickkopf-1 and c-MYC

et al. 2011

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SOX2 is a well-known core transcription factor in embryonic stem cells (ESCs) and has an important role in the maintenance of pluripotency. Recently, SOX2 expression has also been reported in adult stem cells (ASCs), but the role of SOX2 in ASCs remains unknown. In this study, we examined the molecular mechanisms of SOX2 in human mesenchymal stem cells (hMSCs), a type of ASCs, by performing inhibition studies. SOX2 inhibition resulted in altered cell growth and differentiation capabilities. These changes coincided with a decrease in Dickkopf-1 (DKK1), a soluble inhibitor of WNT signaling. Chromatin immunoprecipitation and luciferase assays showed that SOX2 binds to DKK1 and has a positive regulatory role in transcription. The enforced expression of DKK1 in SOX2-inhibited hMSCs reversed the differentiation deformities, but could not abrogate the cell proliferation defect. Proliferation was regulated by c-MYC, whose expression can also be controlled by SOX2. Our study shows that SOX2 directly regulates DKK1 expression and, as a consequence, determines the differentiation lineage of hMSCs. Moreover, SOX2 also regulates proliferation by affecting c-MYC. Therefore, these results suggest that SOX2 might have a specific function by regulating DKK1 and c-MYC in the differentiation and growth of ASCs, which is separate from its roles in ESCs.

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Section: Discussionmentioning

confidence: 84%

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confidence: 99%

SOX2 has a crucial role in the lineage determination and proliferation of mesenchymal stem cells through Dickkopf-1 and c-MYC

et al. 2011

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“…In this study, autocrine IGF-1 levels maintain an elevated baseline activity of ERK1/2 signaling required for enhanced self-renewal (higher OCT4), endodermal (higher CYP51) and mesodermal (higher SM22 α ) potential, but weakened neuronal potential (lower Nestin) [84]. Another growth factor which is basic fibroblast growth factor (bFGF) was shown to be required in maintaining stemness and proliferation in hESCs [31, 85] and in MSCs [80, 86, 87]. Further investigation showed that this bFGF effect was mediated via the IGF system that is upregulated by an autonomous expression of IGF-1R, IGF-1, and IGF-2, as shown in umbilical cord MSCs [86].…”

Section: The Role Of Igfs In Msc Multipotency and Self-renewalmentioning

confidence: 99%

“…Another growth factor which is basic fibroblast growth factor (bFGF) was shown to be required in maintaining stemness and proliferation in hESCs [31, 85] and in MSCs [80, 86, 87]. Further investigation showed that this bFGF effect was mediated via the IGF system that is upregulated by an autonomous expression of IGF-1R, IGF-1, and IGF-2, as shown in umbilical cord MSCs [86]. Although both IGF-1 and IGF-2 are involved in mediating stem cell fate changes, IGF-2 appears to be more prominent than IGF-1 in promoting MSC pluripotency/self-renewal.…”

Section: The Role Of Igfs In Msc Multipotency and Self-renewalmentioning

confidence: 99%

The Roles of Insulin-Like Growth Factors in Mesenchymal Stem Cell Niche

Youssef

Aboalola

Han

2017

Stem Cells International

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Many tissues contain adult mesenchymal stem cells (MSCs), which may be used in tissue regeneration therapies. However, the MSC availability in most tissues is limited which demands expansion in vitro following isolation. Like many developing cells, the state of MSCs is affected by the surrounding microenvironment, and mimicking this natural microenvironment that supports multipotent or differentiated state in vivo is essential to understand for the successful use of MSC in regenerative therapies. Many researchers are, therefore, optimizing cell culture conditions in vitro by altering growth factors, extracellular matrices, chemicals, oxygen tension, and surrounding pH to enhance stem cells self-renewal or differentiation. Insulin-like growth factors (IGFs) system has been demonstrated to play an important role in stem cell biology to either promote proliferation and self-renewal or enhance differentiation onset and outcome, depending on the cell culture conditions. In this review, we will describe the importance of IGFs, IGF-1 and IGF-2, in development and in the MSC niche and how they affect the pluripotency or differentiation towards multiple lineages of the three germ layers.

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“…Human UCB-MSCs and ARPE-19 cells were cultured as previously described [51518]. For RPE differentiation of human UCB-MSCs and AESCs, cells were cultured on culture dishes with the cell culture medium described above.…”

Section: Methodsmentioning

confidence: 99%

Inhibition by miR-410 facilitates direct retinal pigment epithelium differentiation of umbilical cord blood-derived mesenchymal stem cells

et al. 2017

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Retinal pigment epithelium (RPE) is a major component of the eye. This highly specialized cell type facilitates maintenance of the visual system. Because RPE loss induces an irreversible visual impairment, RPE generation techniques have recently been investigated as a potential therapeutic approach to RPE degeneration. The microRNA-based technique is a new strategy for producing RPE cells from adult stem cell sources. Previously, we identified that antisense microRNA-410 (anti-miR-410) induces RPE differentiation from amniotic epithelial stem cells. In this study, we investigated RPE differentiation from umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) via anti-miR-410 treatment. We identified miR-410 as a RPE-relevant microRNA in UCB-MSCs from among 21 putative human RPE-depleted microRNAs. Inhibition of miR-410 induces overexpression of immature and mature RPE-specific factors, including MITF, LRAT, RPE65, Bestrophin, and EMMPRIN. The RPE-induced cells were able to phagocytize microbeads. Results of our microRNA-based strategy demonstrated proof-of-principle for RPE differentiation in UCB-MSCs by using anti-miR-410 treatment without the use of additional factors or exogenous transduction.

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bFGF enhances the IGFs-mediated pluripotent and differentiation potentials in multipotent stem cells

Cited by 22 publications

References 39 publications

SOX2 has a crucial role in the lineage determination and proliferation of mesenchymal stem cells through Dickkopf-1 and c-MYC

SOX2 has a crucial role in the lineage determination and proliferation of mesenchymal stem cells through Dickkopf-1 and c-MYC

The Roles of Insulin-Like Growth Factors in Mesenchymal Stem Cell Niche

Inhibition by miR-410 facilitates direct retinal pigment epithelium differentiation of umbilical cord blood-derived mesenchymal stem cells

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