Additive Effect of BFGF and Selenium on Expansion and Paracrine Action of Human Amniotic Fluid-derived Mesenchymal Stem Cells

Overview

Journal Stem Cell Res Ther

Publisher Biomed Central

Date 2018 Nov 10

PMID 30409167

Citations 22

Authors

Junghyun Park

Jung Han Lee

Byung Sun Yoon

Eun Kyoung Jun

Gilju Lee

In Yong Kim

Seungkwon You

Affiliations

Soon will be listed here.

Abstract

Background: Mesenchymal stem cell-derived conditioned medium (MSC-CM) has emerged as a promising cell-free tool for restoring degenerative diseases and treating traumatic injuries. The present study describes the effect of selenium as a reactive oxygen species (ROS) scavenger and its additive effect with basic fibroblast growth factor (bFGF) on in vitro expansion of amniotic fluid (AF)-MSCs and the paracrine actions of AF-MSC-CM as well as the associated cellular and molecular mechanisms.

Methods: In this study, we obtained CM from human AF-MSCs cultured with selenium. The stemness of selenium-treated AF-MSCs was evaluated by cell growth and differentiation potential. Human fibroblasts were treated with AF-MSC-CM and analyzed for cell signaling changes. For in vivo wound healing assay, ICR mice with a full-thickness skin wound were used.

Results: Selenium played a critical role in in vitro expansion of AF-MSCs through activation of the AKT-ERK1/2, Smad2, and Stat3 signaling pathways along with inactivation of GSK3β. When administered together with bFGF, it showed remarkable effect in inhibiting ROS accumulation and preserving their multipotency. Proliferation and migration of human dermal fibroblasts and in vivo wound healing were improved in the CMs derived from AF-MSCs exposed to selenium and bFGF, which was caused by the Smad2, AKT-MEK1/2-ERK, and NFκB signaling triggered by the paracrine factors of AF-MSCs, such as TGF-β, VEGF, and IL-6. Our results suggest the following: (a) supplementation of selenium in AF-MSC culture contributes to in vitro expansion and preservation of multipotency, (b) ROS accumulation causes progressive losses in proliferative and differentiation potential, (c) the separate activities of bFGF and selenium in MSCs exert an additive effect when used together, and (d) the additive combination improves the therapeutic effects of AF-MSC-derived CMs on tissue repair and regeneration.

Conclusion: Antioxidants, such as selenium, should be considered as an essential supplement for eliciting the paracrine effects of MSC-CMs.

Citing Articles

Evaluation of the impact of customized serum-free culture medium on the production of clinical-grade human umbilical cord mesenchymal stem cells: insights for future clinical applications.

Zhao L, Ni B, Li J, Liu R, Zhang Q, Zheng Z Stem Cell Res Ther. 2024; 15(1):327.

PMID: 39334391 PMC: 11438183. DOI: 10.1186/s13287-024-03949-0.

Effects of nanographene oxide on adipose-derived stem cell cryopreservation.

Li Z, Qi J, Fu S, Luan J, Wang Q Cell Tissue Bank. 2024; 25(3):805-830.

PMID: 38844606 DOI: 10.1007/s10561-024-10140-5.

A Simple High Yield Technique for Isolation of Wharton's Jelly-derived Mesenchymal Stem Cell.

Niknam B, Azizsoltani A, Heidari N, Tokhanbigli S, Alavifard H, Haji Valili M Avicenna J Med Biotechnol. 2024; 16(2):95-103.

PMID: 38618506 PMC: 11007369. DOI: 10.18502/ajmb.v16i2.14860.

Injectable thermosensitive selenium-containing hydrogel as mesenchymal stem cell carrier to improve treatment efficiency in limb ischemia.

Tian X, Yan X, Zang N, Duan W, Wang T, Li X Mater Today Bio. 2024; 25:100967.

PMID: 38312804 PMC: 10835456. DOI: 10.1016/j.mtbio.2024.100967.

Towards the Standardization of Mesenchymal Stem Cell Secretome-Derived Product Manufacturing for Tissue Regeneration.

Chouaib B, Haack-Sorensen M, Chaubron F, Cuisinier F, Collart-Dutilleul P Int J Mol Sci. 2023; 24(16).

PMID: 37628774 PMC: 10454619. DOI: 10.3390/ijms241612594.

References

Walter M, Wright K, Fuller H, MacNeil S, Johnson W . Mesenchymal stem cell-conditioned medium accelerates skin wound healing: an in vitro study of fibroblast and keratinocyte scratch assays. Exp Cell Res. 2010; 316(7):1271-81. DOI: 10.1016/j.yexcr.2010.02.026. View

Kern S, Eichler H, Stoeve J, Kluter H, Bieback K . Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006; 24(5):1294-301. DOI: 10.1634/stemcells.2005-0342. View

Nekanti U, Mohanty L, Venugopal P, Balasubramanian S, Totey S, Ta M . Optimization and scale-up of Wharton's jelly-derived mesenchymal stem cells for clinical applications. Stem Cell Res. 2010; 5(3):244-54. DOI: 10.1016/j.scr.2010.08.005. View

Devasagayam T, Tilak J, Boloor K, Sane K, Ghaskadbi S, Lele R . Free radicals and antioxidants in human health: current status and future prospects. J Assoc Physicians India. 2005; 52:794-804. View

Coutu D, Galipeau J . Roles of FGF signaling in stem cell self-renewal, senescence and aging. Aging (Albany NY). 2011; 3(10):920-33. PMC: 3229969. DOI: 10.18632/aging.100369. View

Imhoff B, Hansen J . Differential redox potential profiles during adipogenesis and osteogenesis. Cell Mol Biol Lett. 2011; 16(1):149-61. PMC: 6275997. DOI: 10.2478/s11658-010-0042-0. View

Yang Y, Xia T, Zhi W, Wei L, Weng J, Zhang C . Promotion of skin regeneration in diabetic rats by electrospun core-sheath fibers loaded with basic fibroblast growth factor. Biomaterials. 2011; 32(18):4243-54. DOI: 10.1016/j.biomaterials.2011.02.042. View

Zhu Z, Cai W, Wang T, Ye H, Ting Zhu Y, Chi L . bFGF-Regulating MAPKs Are Involved in High Glucose-Mediated ROS Production and Delay of Vascular Endothelial Cell Migration. PLoS One. 2015; 10(12):e0144495. PMC: 4671674. DOI: 10.1371/journal.pone.0144495. View

Tracy L, Minasian R, Caterson E . Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound. Adv Wound Care (New Rochelle). 2016; 5(3):119-136. PMC: 4779293. DOI: 10.1089/wound.2014.0561. View

10.

Tsai M, Hwang S, Tsai Y, Cheng F, Lee J, Chang Y . Clonal amniotic fluid-derived stem cells express characteristics of both mesenchymal and neural stem cells. Biol Reprod. 2005; 74(3):545-51. DOI: 10.1095/biolreprod.105.046029. View

11.

McDonald J, Pilgram T . Nuclear expression of p53, p21 and cyclin D1 is increased in bronchioloalveolar carcinoma. Histopathology. 1999; 34(5):439-46. DOI: 10.1046/j.1365-2559.1999.00632.x. View

12.

Paradies G, Petrosillo G, Paradies V, Ruggiero F . Oxidative stress, mitochondrial bioenergetics, and cardiolipin in aging. Free Radic Biol Med. 2010; 48(10):1286-95. DOI: 10.1016/j.freeradbiomed.2010.02.020. View

13.

Schiller M, Javelaud D, Mauviel A . TGF-beta-induced SMAD signaling and gene regulation: consequences for extracellular matrix remodeling and wound healing. J Dermatol Sci. 2004; 35(2):83-92. DOI: 10.1016/j.jdermsci.2003.12.006. View

14.

FROST D, Lish P . Selenium in biology. Annu Rev Pharmacol. 1975; 15:259-84. DOI: 10.1146/annurev.pa.15.040175.001355. View

15.

Helmy M, Ismail S, Fayed H, El-Bassiouni E . Effect of selenium supplementation on the activities of glutathione metabolizing enzymes in human hepatoma Hep G2 cell line. Toxicology. 2000; 144(1-3):57-61. DOI: 10.1016/s0300-483x(99)00190-0. View

16.

Jackson W, Nesti L, Tuan R . Concise review: clinical translation of wound healing therapies based on mesenchymal stem cells. Stem Cells Transl Med. 2012; 1(1):44-50. PMC: 3727688. DOI: 10.5966/sctm.2011-0024. View

17.

Mehta S, Kumari S, Mendelev N, Li P . Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia. BMC Neurosci. 2012; 13:79. PMC: 3411431. DOI: 10.1186/1471-2202-13-79. View

18.

De Miguel M, Fuentes-Julian S, Blazquez-Martinez A, Pascual C, Aller M, Arias J . Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med. 2012; 12(5):574-91. DOI: 10.2174/156652412800619950. View

19.

Roth M, Spaniol K, Kordes C, Schwarz S, Mertsch S, Haussinger D . The Influence of Oxygen on the Proliferative Capacity and Differentiation Potential of Lacrimal Gland-Derived Mesenchymal Stem Cells. Invest Ophthalmol Vis Sci. 2015; 56(8):4741-52. DOI: 10.1167/iovs.14-15475. View

20.

Moon J, Kwak S, Park G, Jung H, Yoon B, Park J . Isolation and characterization of multipotent human keloid-derived mesenchymal-like stem cells. Stem Cells Dev. 2008; 17(4):713-24. DOI: 10.1089/scd.2007.0210. View