Influence of fibroblast growth factor 2 on stem cells in vitro
DOI:
https://doi.org/10.17533/udea.acbi.v41n111a03Keywords:
FGF-2, cell proliferation, senescence, cellular therapyAbstract
The interest and need to study stem cells in regenerative therapies has increased in recent years due to their ability to proliferate and differentiate into multiple lineages. Unfortunately, the number of cells needed for a successful transplant is greater than that obtained directly from the patient, so in vitro cultures of stem cells must be done. However, over time the cells in these cultures become senescent, decreasing their number of cellular divisions and their proliferative capacity. To solve this problem, different growth factors have been proposed as promoting agents for cell proliferation. Among these is the fibroblast growth factor 2 which, when added to the medium, could promote proliferation and increase the life time of the cells in the culture. The following review compiles information about the biology of this growth factor and the type of signaling it uses, as well as its applications in regenerative therapy and its effect on cell proliferation and senescence.
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Ahn H-J, Lee W, Kwack K, Kwon Y. 2009. FGF2 stimulates the proliferation of human mesenchymal stem cells through the transient activation of JNK signaling. FEBS Letters, 583(17): 2922-2926. DOI: 10.1016/j.febslet.2009.07.056
Apel A, Groth A, Schlesinger S, Bruns H, Schemmer P, Büchler MW, Herr I. 2009. Suitability of human mesenchymal stem cells for gene therapy depends on the expansion medium. Experimental Cell Research, 315(3): 498-507. DOI: 10.1016/j.yexcr.2008.11.013
Baker N, Boyette L, Tuan-R S. 2015. Characterization of bone marrow-derived mesenchymal stem cells in aging. Bone, 70: 37-47. DOI: 10.1016/j.bone.2014.10.014
Bianchi G, Banfi A, Mastrogiacomo M, Notaro R, Luzzatto L, Cancedda R, Quarto R. 2003. Ex vivo enrichment of mesenchymal cell progenitors by fibroblast growth factor 2. Experimental Cell Research, 287(1): 98-105. DOI: 10.1016/s0014-4827(03)00138-1
Brewer JR, Mazot P, Soriano P. 2016. Genetic insights into the mechanisms of Fgf signaling. Genes and Development, 30(7): 751-771. DOI: 10.1101/gad.277137.115
Brizuela C, Galleguillos S, Carrión F, Cabrera C, Luz P, Inostroza C. 2013. Aislación y caracterización de células madre mesenquimales provenientes de pulpa y folículo dentario humano. International Journal of Morphology, 31(2): 739-746. DOI: 10.4067/S0717-95022013000200063
Can A, Celikkan F T, Cinar O. 2017. Umbilical cord mesenchymal stromal cell transplantations: A systemic analysis of clinical trials. Cytotherapy, 19(12): 1351-1382. DOI: 10.1016/j.jcyt.2017.08.004
Carvalho PH, Daibert F, Monteiro BS, Okano BS, Carvalho JL, Cunha D, Cunha LS, Favarato V, Pereira, Augusto L, Carlo R. 2013. Differentiation of adipose tissue-derived mesenchymal stem cells into cardiomyocytes. Arquivos Brasileiros de Cardiologia, 100(1): 82-89. DOI: 10.1590/s0066-782x2012005000114
Chen G, Yue A, Ruan Z, Yin Y, Wang R, Ren Y, Zhu L. 2015. Comparison of biological characteristics of mesenchymal stem cells derived from maternal-origin placenta and Wharton’s jelly. Stem Cell Research and Therapy, 6(1): 228-234. DOI: 10.1186/s13287-015-0219-6
Chen T M, Chen Y H, Sun H S, Tsai S J. 2019. Fibroblast growth factors: Potential novel targets for regenerative therapy of osteoarthritis. Chinese Journal of Physiology, 62(1): 2-10. DOI: 10.4103/CJP.CJP_11_19
Coutu DL, François M, Galipeau J. 2011. Inhibition of cellular senescence by developmentally regulated FGF receptors in mesenchymal stem cells. Blood, 117(25): 6801-6812. DOI: 10.1182/blood-2010-12-321539
Cui Y, Ma S, Zhang C, Cao W, Liu M, Li D, Xing Q, Qu R, Yao, N. 2017. Human umbilical cord mesenchymal stem cells transplantation improves cognitive function in Alzheimer’s disease mice by decreasing oxidative stress and promoting hippocampal neurogenesis. Behavioural Brain Research, 320: 291-301. DOI: 10.1016/j.bbr.2016.12.021
Dermargos A, Armelin H. 2007. FGF-2: estudo de estrutura e função [Tesis de Doctorado]. [São Paulo (Brasil)], Universidade de São Paulo.
Dolivo D, Hernandez S, Dominko T. 2016. Cellular lifespan and senescence: a complex balance between multiple cellular pathways. Bioessays, 38: S33-44. DOI: 10.1002/bies.201670906
Drela K, Sarnowska A, Siedlecka P, Szablowska-Gadomska I, Wielgos M, Jurga M, Lukomska B, Domanska-Janik K. 2014. Low oxygen atmosphere facilitates proliferation and maintains undifferentiated state of umbilical cord mesenchymal stem cells in an hypoxia inducible factor-dependent manner. Cytotherapy, 16(7): 881-892. DOI: 10.1016/j.jcyt.2014.02.009
El Agha E, Kosanovic D, Schermuly RT, Bellusci S. 2016. Role of fibroblast growth factors in organ regeneration and repair. In Seminars in Cell and Developmental Biology, 53: 76-84. DOI: 10.1016/j.semcdb.2015.10.009
Endo K, Fujita N, Nakagawa T, Nishimura R. 2019. Effect of fibroblast growth factor-2 and serum on canine mesenchymal stem cell chondrogenesis. Tissue Engineering Part A, 25(11-12): 901-910. DOI: 10.1089/ten.TEA.2018.0177
Eom YW, Oh JE, Lee JI, Baik SK, Rhee KJ, Shin HC, Kim C, Ahn J, Kong J, Shim K. 2014. The role of growth factors in maintenance of stemness in bone marrow-derived mesenchymal stem cells. Biochemical and Biophysical Research Communications, 445(1): 16-22. DOI: 10.1016/j.bbrc.2014.01.084
Espinoza F, Aliaga F, Crawford PL. 2016. Escenario actual y perspectivas de la terapia con células madre mesenquimales en medicina intensiva. Revista Médica de Chile, 144(2): 222-231. DOI: 10.4067/S0034-98872016000200011
Fernandes-Freitas I, Owen BM. 2015. Metabolic roles of endocrine fibroblast growth factors. Current Opinion in Pharmacology, 25: 30-35. DOI: 10.1016/j.coph.2015.09.014
Guo YL, Chakraborty S, Rajan SS, Wang R, Huang F. 2010. Effects of oxidative stress on mouse embryonic stem cell proliferation, apoptosis, senescence, and self-renewal. Stem Cells and Development, 19(9): 1321-1331. DOI: 10.1089/scd.2009.0313
Haghighi F, Dahlmann J, Nakhaei-Rad S, Lang A, Kutschka I, Zenker M, Kensah R, Piekorz R, Ahmadian MR. 2018. bFGF-mediated pluripotency maintenance in human induced pluripotent stem cells is associated with NRAS-MAPK signaling. Cell Communication and Signaling, 16(1): 96-109. DOI: 10.1186/s12964-018-0307-1
Hernández BM, Inostroza VC, Carrión AF, Chaparro PA, Quintero HA, Sanz RA. 2011. Proliferación de células madres mesenquimales obtenidas de tejido gingival humano sobre una matriz de quitosano: estudio in vitro. Revista Clínica de Periodoncia, Implantología y Rehabilitación Oral, 4(2): 59-63. DOI: 10.4067/S0719-01072011000200004
Hong SH, Lee MH, Koo MA, Seon GM, Park YJ, Kim D, Park JC. 2019. Stem cell passage affects directional migration of stem cells in electrotaxis. Stem Cell Research, 38: 101475. DOI: 10.1016/j.scr.2019.101475
Huang L, Wong YP, Gu H, Cai YJ, Ho Y, Wang CC, Leung T, Burd A. 2011. Stem cell-like properties of human umbilical cord lining epithelial cells and the potential for epidermal reconstitution. Cytotherapy, 13(2): 145-155. DOI: 10.3109/14653249.2010.509578
Ito T, Sawada R, Fujiwara Y, Seyama Y, Tsuchiya T. 2007. FGF-2 suppresses cellular senescence of human mesenchymal stem cells by down-regulation of TGF-β2. Biochemical and Biophysical Research Communications, 359(1): 108-114. DOI: 10.1016/j.bbrc.2007.05.067
Katsares V, Petsa A, Felesakis A, Paparidis Z, Nikolaidou E, Gargani S, Karvounidou I, Ardelean K, Grigoriadis J. 2009. A rapid and accurate method for the stem cell viability evaluation: the case of the thawed umbilical cord blood. Laboratory Medicine, 40(9): 557-560. DOI: 10.1309/LMLE8BVHYWCT82CL
Korsensky L, Ron D. 2016. Regulation of FGF signaling: recent insights from studying positive and negative modulators. Seminars in Cell and Developmental Biology, 53: 101-114. DOI: 10.1016/j.semcdb.2016.01.023
Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP, Baum MG, Schiavi S, Hu MC, Moe OW, Kuro-o M. 2006. Regulation of fibroblast growth factor-23 signaling by Klotho. The Journal of Biological Chemistry, 281: 6120-6123. DOI:10.1074/jbc.C500457200
Lai WT, Krishnappa V, Phinney DG. 2011. Fibroblast growth factor 2 (Fgf2) inhibits differentiation of mesenchymal stem cells by inducing Twist2 and Spry4, blocking extracellular regulated kinase activation, and altering Fgf receptor expression levels. Stem Cells, 29(7): 1102-1111. DOI: 10.1002/stem.661
Lee JS, Kim SK, Jung BJ, Choi SB, Choi EY, Kim CS. 2018. Enhancing proliferation and optimizing the culture condition for human bone marrow stromal cells using hypoxia and fibroblast growth factor-2. Stem Cell Research, 28: 87-95. DOI: 10.1016/j.scr.2018.01.010
Markan KR, Potthoff MJ. 2016. Metabolic fibroblast growth factors (FGFs): mediators of energy homeostasis. Seminars in Cell and Developmental Biology, 53: 85-93. DOI: 10.1016/j.semcdb.2015.09.021
Meng X, Xue M, Xu P, Hu F, Sun B, Xiao Z. 2017. MicroRNA profiling analysis revealed different cellular senescence mechanisms in human mesenchymal stem cells derived from different origin. Genomics, 109(3-4): 147-157. DOI: 10.1016/j.ygeno.2017.02.003
Naugler WE, Tarlow BD, Fedorov LM, Taylor M, Pelz C, Li B, Darnell J, Grompe M. 2015. Fibroblast growth factor signaling controls liver size in mice with humanized livers. Gastroenterology, 149(3): 728-740. DOI: 10.1053/j.gastro.2015.05.043
Nawrocka D, Kornicka K, Szydlarska J, Marycz K. 2017. Basic fibroblast growth factor inhibits apoptosis and promotes proliferation of adipose-derived mesenchymal stromal cells isolated from patients with type 2 diabetes by reducing cellular oxidative stress. Oxidative Medicine and Cellular Longevity, 2017: 3027109. DOI: 10.1155/2017/3027109
Novais A, Lesieur J, Sadoine J, Slimani L, Baroukh B, Saubaméa B, Schmitt A, Vital S, Rochefort GY. 2019. Priming Dental Pulp Stem Cells from Human Exfoliated Deciduous Teeth with Fibroblast Growth Factor‐2 Enhances Mineralization Within Tissue‐Engineered Constructs Implanted in Craniofacial Bone Defects. Stem Cells Translational Medicine, 8(8): 844-857. DOI: 10.1002/sctm.18-0182
Nowwarote N, Pavasant P, Osathanon T. 2015. Role of endogenous basic fibroblast growth factor in stem cells isolated from human exfoliated deciduous teeth. Archives of Oral Biology, 60(3): 408-415. DOI: 10.1016/j.archoralbio.2014.11.017
Ornitz DM, Itoh N. 2001. Fibroblast growth factors. Genome Biology, 2(3): reviews3005.1–3005.12. DOI :10.1186/gb-2001-2-3-reviews3005
Park J, Lee JH, Yoon BS, Jun EK, Lee G, Kim IY, You S. 2018. Additive effect of bFGF and selenium on expansion and paracrine action of human amniotic fluid-derived mesenchymal stem cells. Stem Cell Research and Therapy, 9(1): 293-309. DOI: 10.1186/s13287-018-1058-z
Preda MB, Rosca AM, Tutuianu R, Burlacu A. 2015. Pre-stimulation with FGF-2 increases in vitro functional coupling of mesenchymal stem cells with cardiac cells. Biochemical and Biophysical Research Communications, 464(2): 667-673. DOI: 10.1016/j.bbrc.2015.07.055
Quimby JM, Borjesson DL. 2018. Mesenchymal stem cell therapy in cats: Current knowledge and future potential. Journal of Feline Medicine and Surgery, 20(3): 208-216. DOI: 10.1177/1098612X18758590
Richardson SM, Kalamegam G, Pushparaj PN, Matta C, Memic A, Khademhosseini A, Mobasheri R, Poletti F, Hoyland JA, Mobasheri A. 2016. Mesenchymal stem cells in regenerative medicine: focus on articular cartilage and intervertebral disc regeneration. Methods, 99: 69-80. DOI: 10.1016/j.ymeth.2015.09.015
Sah JP, Hao NTT, Kim Y, Eigler T, Tzahor E, Kim SH, Hwang Y, Yoon JK. 2019. MBP-FGF2-Immobilized Matrix Maintains Self-Renewal and Myogenic Differentiation Potential of Skeletal Muscle Stem Cells. International Journal of Stem Cells, 12(2):360-366. DOI: 10.15283/ijsc18125
Taupin P, Ray J, Fischer WH, Suhr ST, Hakansson K, Grubb A, Gage FH. 2000. FGF-2-responsive neural stem cell proliferation requires CCg, a novel autocrine/paracrine cofactor. Neuron, 28(2): 385-397. DOI: 10.1016/S0896-6273(00)00119-7
Wang JJ, Liu YL, Sun YC, Ge W, Wang YY, Dyce PW, Hou R, Shen W. 2015. Basic fibroblast growth factor stimulates the proliferation of bone marrow mesenchymal stem cells in giant panda (ailuropoda melanoleuca). PloS One, 10(9): e0137712. DOI: 10.1371/journal.pone.0137712
Wang X, Ma S, Yang B, Huang T, Meng N, Xu L, Xing Q, Zhang Y, Li Q, Zhang T. 2018. Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer’s disease. Behavioural Brain Research, 339: 297-304. DOI: 10.1016/j.bbr.2017.10.032
Yang Y. 2018. Aging of mesenchymal stem cells: Implication in regenerative medicine. Regenerative Therapy, 9: 120-122. DOI:10.1016/j.reth.2018.09.002
Yonemitsu R, Tokunaga T, Shukunami C, Ideo K, Arimura H, Karasugi T, Nakamura J, Ide J, Hiraki Y, Mizuta H. 2019. Fibroblast Growth Factor 2 Enhances Tendon-to-Bone Healing in a Rat Rotator Cuff Repair of Chronic Tears. The American Journal of Sports Medicine, 47(7): 1701-1712. DOI: 10.1177/0363546519836959
Zhai W, Yong D, El-Jawhari JJ, Cuthbert R, Mcgonagle D, Naing MW, Jones E. 2019. Identification of senescent cells in multipotent mesenchymal stromal cell cultures: current methods and future directions. Cytotherapy, S1465-3249(19)30752-2. DOI: 10.1016/j.jcyt.2019.05.001
Zhang J, Li Y. 2016. Therapeutic uses of FGFs. Seminars in Cell and Developmental Biology, 53: 144-154. DOI: 10.1016/j.semcdb.2015.09.007
Zheng W, Nowakowski RS, Vaccarino FM. 2004. Fibroblast growth factor 2 is required for maintaining the neural stem cell pool in the mouse brain subventricular zone. Developmental Neuroscience, 26(2-4): 181-196. DOI: 10.1159/000082136
Ziaei M, Zhang J, Patel DV, McGhee CN. 2017. Umbilical cord stem cells in the treatment of corneal disease. Survey of Ophthalmology, 62(6): 803-815. DOI: 10.1016/j.survophthal.2017.02.002
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