Abstract
Mesenchymal Stem Cells (MSCs) are distributed in many parts of the human body, including the bone marrow, placenta, umbilical cord, fat, and nasal mucosa. One of the unique features of MSCs is their multidirectional differentiation potential, including the ability to undergo osteogenesis, adipogenesis, and chondrogenesis, and to produce neurons, endothelial cells, Schwann cells, medullary nucleus cells, cardiomyocytes, and alveolar epithelial cells. MSCs have thus become a hot research topic in recent years. Numerous studies have investigated the differentiation of MSCs into various types of cells in vitro and their application to numerous fields. However, most studies have cultured MSCs under atmospheric oxygen tension with an oxygen concentration of 21%, which does not reflect a normal physiological state, given that the oxygen concentration generally used in vitro is four to ten times that to which MSCs would be exposed in the body. We therefore review the growing number of studies exploring the effect of hypoxic preconditioning on the differentiation of MSCs.
Keywords: Hypoxic preconditioning, mesenchymal stem cell, differentiation.
[1]
Bruder SP, Jaiswal N, Ricalton NS, Mosca JD, Kraus KH, Kadiyala S. Mesenchymal stem cells in osteobiology and applied bone regeneration. Clin Orthop Relat Res 1998; (355)(Suppl.): S247-56.
[http://dx.doi.org/10.1097/00003086-199810001-00025] [PMID: 9917644]
[http://dx.doi.org/10.1097/00003086-199810001-00025] [PMID: 9917644]
[2]
Oliveira PH, Boura JS, Abecasis MM, Gimble JM, da Silva CL, Cabral JMS. Impact of hypoxia and long-term cultivation on the genomic stability and mitochondrial performance of ex vivo expanded human stem/stromal cells. Stem Cell Res (Amst) 2012; 9(3): 225-36.
[http://dx.doi.org/10.1016/j.scr.2012.07.001] [PMID: 22903042]
[http://dx.doi.org/10.1016/j.scr.2012.07.001] [PMID: 22903042]
[3]
Samsonraj RM, Raghunath M, Hui JH, Ling L, Nurcombe V, Cool SM. Telomere length analysis of human mesenchymal stem cells by quantitative PCR. Gene 2013; 519(2): 348-55.
[http://dx.doi.org/10.1016/j.gene.2013.01.039] [PMID: 23380569]
[http://dx.doi.org/10.1016/j.gene.2013.01.039] [PMID: 23380569]
[4]
Aust L, Devlin B, Foster SJ, et al. Yield of human adipose-derived adult stem cells from liposuction aspirates. Cytotherapy 2004; 6(1): 7-14.
[http://dx.doi.org/10.1080/14653240310004539] [PMID: 14985162]
[http://dx.doi.org/10.1080/14653240310004539] [PMID: 14985162]
[5]
Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284(5411): 143-7.
[http://dx.doi.org/10.1126/science.284.5411.143] [PMID: 10102814]
[http://dx.doi.org/10.1126/science.284.5411.143] [PMID: 10102814]
[6]
Trachtenberg B, Velazquez DL, Williams AR, et al. Rationale and design of the Transendocardial Injection of Autologous Human Cells (bone marrow or mesenchymal) in Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction (TAC-HFT) trial: A randomized, double-blind, placebo-controlled study of safety and efficacy. Am Heart J 2011; 161(3): 487-93.
[http://dx.doi.org/10.1016/j.ahj.2010.11.024] [PMID: 21392602]
[http://dx.doi.org/10.1016/j.ahj.2010.11.024] [PMID: 21392602]
[7]
Hare JM, Fishman JE, Gerstenblith G, et al. Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA 2012; 308(22): 2369-79.
[http://dx.doi.org/10.1001/jama.2012.25321] [PMID: 23117550]
[http://dx.doi.org/10.1001/jama.2012.25321] [PMID: 23117550]
[8]
Tan J, Wu W, Xu X, et al. Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial. JAMA 2012; 307(11): 1169-77.
[http://dx.doi.org/10.1001/jama.2012.316] [PMID: 22436957]
[http://dx.doi.org/10.1001/jama.2012.316] [PMID: 22436957]
[9]
Skiles ML, Sahai S, Rucker L, Blanchette JO. Use of culture geometry to control hypoxia-induced vascular endothelial growth factor secretion from adipose-derived stem cells: optimizing a cell-based approach to drive vascular growth. Tissue Eng Part A 2013; 19(21-22): 2330-8.
[http://dx.doi.org/10.1089/ten.tea.2012.0750] [PMID: 23668629]
[http://dx.doi.org/10.1089/ten.tea.2012.0750] [PMID: 23668629]
[10]
Portron S, Merceron C, Gauthier O, et al. Effects of in vitro low oxygen tension preconditioning of adipose stromal cells on their in vivo chondrogenic potential: application in cartilage tissue repair. PLoS One 2013; 8(4): e62368
[http://dx.doi.org/10.1371/journal.pone.0062368] [PMID: 23638053]
[http://dx.doi.org/10.1371/journal.pone.0062368] [PMID: 23638053]
[11]
Choi JR, Pingguan-Murphy B, Wan Abas WA, et al. In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis. PLoS One 2015; 10(1): e0115034
[http://dx.doi.org/10.1371/journal.pone.0115034] [PMID: 25615717]
[http://dx.doi.org/10.1371/journal.pone.0115034] [PMID: 25615717]
[12]
Efimenko A, Starostina E, Kalinina N, Stolzing A. Angiogenic properties of aged adipose derived mesenchymal stem cells after hypoxic conditioning. J Transl Med 2011; 9: 10.
[http://dx.doi.org/10.1186/1479-5876-9-10] [PMID: 21244679]
[http://dx.doi.org/10.1186/1479-5876-9-10] [PMID: 21244679]
[13]
Rosová I, Dao M, Capoccia B, Link D, Nolta JA. Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem Cells 2008; 26(8): 2173-82.
[http://dx.doi.org/10.1634/stemcells.2007-1104] [PMID: 18511601]
[http://dx.doi.org/10.1634/stemcells.2007-1104] [PMID: 18511601]
[14]
Cipolleschi MG, Dello Sbarba P, Olivotto M. The role of hypoxia in the maintenance of hematopoietic stem cells. Blood 1993; 82(7): 2031-7.
[http://dx.doi.org/10.1182/blood.V82.7.2031.2031] [PMID: 8104535]
[http://dx.doi.org/10.1182/blood.V82.7.2031.2031] [PMID: 8104535]
[15]
Packer L, Fuehr K. Low oxygen concentration extends the lifespan of cultured human diploid cells. Nature 1977; 267(5610): 423-5.
[http://dx.doi.org/10.1038/267423a0] [PMID: 876356]
[http://dx.doi.org/10.1038/267423a0] [PMID: 876356]
[16]
Martin-Rendon E, Hale SJM, Ryan D, et al. Transcriptional profiling of human cord blood CD133+ and cultured bone marrow mesenchymal stem cells in response to hypoxia. Stem Cells 2007; 25(4): 1003-12.
[http://dx.doi.org/10.1634/stemcells.2006-0398] [PMID: 17185612]
[http://dx.doi.org/10.1634/stemcells.2006-0398] [PMID: 17185612]
[17]
Holzwarth C, Vaegler M, Gieseke F, et al. Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells. BMC Cell Biol 2010; 11: 11.
[http://dx.doi.org/10.1186/1471-2121-11-11] [PMID: 20109207]
[http://dx.doi.org/10.1186/1471-2121-11-11] [PMID: 20109207]
[18]
Tsai CC, Chen YJ, Yew TL, et al. Hypoxia inhibits senescence and maintains mesenchymal stem cell properties through down-regulation of E2A-p21 by HIF-TWIST. Blood 2011; 117(2): 459-69.
[http://dx.doi.org/10.1182/blood-2010-05-287508] [PMID: 20952688]
[http://dx.doi.org/10.1182/blood-2010-05-287508] [PMID: 20952688]
[19]
Nagano M, Kimura K, Yamashita T, et al. Hypoxia responsive mesenchymal stem cells derived from human umbilical cord blood are effective for bone repair. Stem Cells Dev 2010; 19(8): 1195-210.
[http://dx.doi.org/10.1089/scd.2009.0447] [PMID: 20345248]
[http://dx.doi.org/10.1089/scd.2009.0447] [PMID: 20345248]
[20]
Huang J, Deng F, Wang L, et al. Hypoxia induces osteogenesis-related activities and expression of core binding factor α1 in mesenchymal stem cells. Tohoku J Exp Med 2011; 224(1): 7-12.
[http://dx.doi.org/10.1620/tjem.224.7] [PMID: 21498965]
[http://dx.doi.org/10.1620/tjem.224.7] [PMID: 21498965]
[21]
Hung SP, Ho JH, Shih YR, Lo T, Lee OK. Hypoxia promotes proliferation and osteogenic differentiation potentials of human mesenchymal stem cells. J Orthop Res 2012; 30(2): 260-6.
[http://dx.doi.org/10.1002/jor.21517] [PMID: 21809383]
[http://dx.doi.org/10.1002/jor.21517] [PMID: 21809383]
[22]
Wagegg M, Gaber T, Lohanatha FL, et al. Hypoxia promotes osteogenesis but suppresses adipogenesis of human mesenchymal stromal cells in a hypoxia-inducible factor-1 dependent manner. PLoS One 2012; 7(9): e46483
[http://dx.doi.org/10.1371/journal.pone.0046483] [PMID: 23029528]
[http://dx.doi.org/10.1371/journal.pone.0046483] [PMID: 23029528]
[23]
Qiu Y, Chen Y, Zeng T, Guo W, Zhou W, Yang X. EGCG ameliorates the hypoxia-induced apoptosis and osteogenic differentiation reduction of mesenchymal stem cells via upregulating miR-210. Mol Biol Rep 2016; 43(3): 183-93.
[http://dx.doi.org/10.1007/s11033-015-3936-0] [PMID: 26780211]
[http://dx.doi.org/10.1007/s11033-015-3936-0] [PMID: 26780211]
[24]
Volkmer E, Kallukalam BC, Maertz J, et al. Hypoxic preconditioning of human mesenchymal stem cells overcomes hypoxia-induced inhibition of osteogenic differentiation. Tissue Eng Part A 2010; 16(1): 153-64.
[http://dx.doi.org/10.1089/ten.tea.2009.0021] [PMID: 19642854]
[http://dx.doi.org/10.1089/ten.tea.2009.0021] [PMID: 19642854]
[25]
Chung DJ, Hayashi K, Toupadakis CA, Wong A, Yellowley CE. Osteogenic proliferation and differentiation of canine bone marrow and adipose tissue derived mesenchymal stromal cells and the influence of hypoxia. Res Vet Sci 2012; 92(1): 66-75.
[http://dx.doi.org/10.1016/j.rvsc.2010.10.012] [PMID: 21075407]
[http://dx.doi.org/10.1016/j.rvsc.2010.10.012] [PMID: 21075407]
[26]
Cicione C, Muiños-López E, Hermida-Gómez T, Fuentes-Boquete I, Díaz-Prado S, Blanco FJ. Effects of severe hypoxia on bone marrow mesenchymal stem cells differentiation potential. Stem Cells Int 2013; 2013: 232896
[http://dx.doi.org/10.1155/2013/232896] [PMID: 24082888]
[http://dx.doi.org/10.1155/2013/232896] [PMID: 24082888]
[27]
Lu Y, Wei L, Zhang X, et al. The Regulation of Mesenchymal Stem Cell Therapy Through Magnetic Resonance Imaging Agents-Based Cellular Condition and Oxygen Environment. J Biomed Nanotechnol 2018; 14(11): 1906-20.
[http://dx.doi.org/10.1166/jbn.2018.2639] [PMID: 30165927]
[http://dx.doi.org/10.1166/jbn.2018.2639] [PMID: 30165927]
[28]
Li ZH, Liao W, Zhao Q, et al. Effect of Cbfa1 on osteogenic differentiation of mesenchymal stem cells under hypoxia condition. Int J Clin Exp Med 2014; 7(3): 540-8.
[PMID: 24753746]
[PMID: 24753746]
[29]
Tamama K, Kawasaki H, Kerpedjieva SS, Guan J, Ganju RK, Sen CK. Differential roles of hypoxia inducible factor subunits in multipotential stromal cells under hypoxic condition. J Cell Biochem 2011; 112(3): 804-17.
[http://dx.doi.org/10.1002/jcb.22961] [PMID: 21328454]
[http://dx.doi.org/10.1002/jcb.22961] [PMID: 21328454]
[30]
Yang DC, Yang MH, Tsai CC, Huang TF, Chen YH, Hung SC. Hypoxia inhibits osteogenesis in human mesenchymal stem cells through direct regulation of RUNX2 by TWIST. PLoS One 2011; 6(9): e23965
[http://dx.doi.org/10.1371/journal.pone.0023965] [PMID: 21931630]
[http://dx.doi.org/10.1371/journal.pone.0023965] [PMID: 21931630]
[31]
Wang Y, Li J, Wang Y, et al. Effects of hypoxia on osteogenic differentiation of rat bone marrow mesenchymal stem cells. Mol Cell Biochem 2012; 362(1-2): 25-33.
[http://dx.doi.org/10.1007/s11010-011-1124-7] [PMID: 22198287]
[http://dx.doi.org/10.1007/s11010-011-1124-7] [PMID: 22198287]
[32]
Xu N, Liu H, Qu F, et al. Hypoxia inhibits the differentiation of mesenchymal stem cells into osteoblasts by activation of Notch signaling. Exp Mol Pathol 2013; 94(1): 33-9.
[http://dx.doi.org/10.1016/j.yexmp.2012.08.003] [PMID: 22964414]
[http://dx.doi.org/10.1016/j.yexmp.2012.08.003] [PMID: 22964414]
[33]
Hsu SH, Chen CT, Wei YH. Inhibitory effects of hypoxia on metabolic switch and osteogenic differentiation of human mesenchymal stem cells. Stem Cells 2013; 31(12): 2779-88.
[http://dx.doi.org/10.1002/stem.1441] [PMID: 23733376]
[http://dx.doi.org/10.1002/stem.1441] [PMID: 23733376]
[34]
Kim JH, Yoon SM, Song SU, et al. Hypoxia Suppresses Spontaneous Mineralization and Osteogenic Differentiation of Mesenchymal Stem Cells via IGFBP3 Up-Regulation. Int J Mol Sci 2016; 17(9): E1389
[http://dx.doi.org/10.3390/ijms17091389] [PMID: 27563882]
[http://dx.doi.org/10.3390/ijms17091389] [PMID: 27563882]
[35]
Valorani MG, Montelatici E, Germani A, et al. Pre-culturing human adipose tissue mesenchymal stem cells under hypoxia increases their adipogenic and osteogenic differentiation potentials. Cell Prolif 2012; 45(3): 225-38.
[http://dx.doi.org/10.1111/j.1365-2184.2012.00817.x] [PMID: 22507457]
[http://dx.doi.org/10.1111/j.1365-2184.2012.00817.x] [PMID: 22507457]
[36]
Elabd C, Ichim TE, Miller K, et al. Comparing atmospheric and hypoxic cultured mesenchymal stem cell transcriptome: implication for stem cell therapies targeting intervertebral discs. J Transl Med 2018; 16(1): 222.
[http://dx.doi.org/10.1186/s12967-018-1601-9] [PMID: 30097061]
[http://dx.doi.org/10.1186/s12967-018-1601-9] [PMID: 30097061]
[37]
Jiang C, Sun J, Dai Y, et al. HIF-1A and C/EBPs transcriptionally regulate adipogenic differentiation of bone marrow-derived MSCs in hypoxia. Stem Cell Res Ther 2015; 6: 21.
[http://dx.doi.org/10.1186/s13287-015-0014-4] [PMID: 25889814]
[http://dx.doi.org/10.1186/s13287-015-0014-4] [PMID: 25889814]
[38]
Zhou S, Lechpammer S, Greenberger JS, Glowacki J. Hypoxia inhibition of adipocytogenesis in human bone marrow stromal cells requires transforming growth factor-beta/Smad3 signaling. J Biol Chem 2005; 280(24): 22688-96.
[http://dx.doi.org/10.1074/jbc.M412953200] [PMID: 15845540]
[http://dx.doi.org/10.1074/jbc.M412953200] [PMID: 15845540]
[39]
Park IH, Kim KH, Choi HK, et al. Constitutive stabilization of hypoxia-inducible factor alpha selectively promotes the self-renewal of mesenchymal progenitors and maintains mesenchymal stromal cells in an undifferentiated state. Exp Mol Med 2013; 45e44
[http://dx.doi.org/10.1038/emm.2013.87] [PMID: 24071737]
[http://dx.doi.org/10.1038/emm.2013.87] [PMID: 24071737]
[40]
Han YS, Lee JH, Yoon YM, Yun CW, Noh H, Lee SH. Hypoxia-induced expression of cellular prion protein improves the therapeutic potential of mesenchymal stem cells. Cell Death Dis 2016; 7(10): e2395
[http://dx.doi.org/10.1038/cddis.2016.310] [PMID: 27711081]
[http://dx.doi.org/10.1038/cddis.2016.310] [PMID: 27711081]
[41]
Boyette LB, Creasey OA, Guzik L, Lozito T, Tuan RS. Human bone marrow-derived mesenchymal stem cells display enhanced clonogenicity but impaired differentiation with hypoxic preconditioning. Stem Cells Transl Med 2014; 3(2): 241-54.
[http://dx.doi.org/10.5966/sctm.2013-0079] [PMID: 24436440]
[http://dx.doi.org/10.5966/sctm.2013-0079] [PMID: 24436440]
[42]
Yoo HI, Moon YH, Kim MS. Effects of CoCl2 on multi-lineage differentiation of C3H/10T1/2 mesenchymal stem cells. Korean J Physiol Pharmacol 2016; 20(1): 53-62.
[http://dx.doi.org/10.4196/kjpp.2016.20.1.53] [PMID: 26807023]
[http://dx.doi.org/10.4196/kjpp.2016.20.1.53] [PMID: 26807023]
[43]
Leijten J, Georgi N, Moreira Teixeira L, van Blitterswijk CA, Post JN, Karperien M. Metabolic programming of mesenchymal stromal cells by oxygen tension directs chondrogenic cell fate. Proc Natl Acad Sci USA 2014; 111(38): 13954-9.
[http://dx.doi.org/10.1073/pnas.1410977111] [PMID: 25205812]
[http://dx.doi.org/10.1073/pnas.1410977111] [PMID: 25205812]
[44]
Portron S, Hivernaud V, Merceron C, et al. Inverse regulation of early and late chondrogenic differentiation by oxygen tension provides cues for stem cell-based cartilage tissue engineering. Cell Physiol Biochem 2015; 35(3): 841-57.
[http://dx.doi.org/10.1159/000369742] [PMID: 25632940]
[http://dx.doi.org/10.1159/000369742] [PMID: 25632940]
[45]
Cao B, Li Z, Peng R, Ding J. Effects of cell-cell contact and oxygen tension on chondrogenic differentiation of stem cells. Biomaterials 2015; 64: 21-32.
[http://dx.doi.org/10.1016/j.biomaterials.2015.06.018] [PMID: 26113183]
[http://dx.doi.org/10.1016/j.biomaterials.2015.06.018] [PMID: 26113183]
[46]
Lee J, Byeon JS, Lee KS, et al. Chondrogenic potential and anti-senescence effect of hypoxia on canine adipose mesenchymal stem cells. Vet Res Commun 2016; 40(1): 1-10.
[http://dx.doi.org/10.1007/s11259-015-9647-0] [PMID: 26661466]
[http://dx.doi.org/10.1007/s11259-015-9647-0] [PMID: 26661466]
[47]
Bae HC, Park HJ, Wang SY, Yang HR, Lee MC, Han HS. Hypoxic condition enhances chondrogenesis in synovium-derived mesenchymal stem cells. Biomater Res 2018; 22: 28.
[http://dx.doi.org/10.1186/s40824-018-0134-x] [PMID: 30275971]
[http://dx.doi.org/10.1186/s40824-018-0134-x] [PMID: 30275971]
[48]
Lee HH, Chang CC, Shieh MJ, et al. Hypoxia enhances chondrogenesis and prevents terminal differentiation through PI3K/Akt/FoxO dependent anti-apoptotic effect. Sci Rep 2013; 3: 2683.
[http://dx.doi.org/10.1038/srep02683] [PMID: 24042188]
[http://dx.doi.org/10.1038/srep02683] [PMID: 24042188]
[49]
Kanichai M, Ferguson D, Prendergast PJ, Campbell VA. Hypoxia promotes chondrogenesis in rat mesenchymal stem cells: a role for AKT and hypoxia-inducible factor (HIF)-1alpha. J Cell Physiol 2008; 216(3): 708-15.
[http://dx.doi.org/10.1002/jcp.21446] [PMID: 18366089]
[http://dx.doi.org/10.1002/jcp.21446] [PMID: 18366089]
[50]
Taheem DK, Foyt DA, Loaiza S, et al. Differential Regulation of Human Bone Marrow Mesenchymal Stromal Cell Chondrogenesis by Hypoxia Inducible Factor-1α Hydroxylase Inhibitors. Stem Cells 2018; 36(9): 1380-92.
[http://dx.doi.org/10.1002/stem.2844] [PMID: 29726060]
[http://dx.doi.org/10.1002/stem.2844] [PMID: 29726060]
[51]
Ronzière MC, Perrier E, Mallein-Gerin F, Freyria AM. Chondrogenic potential of bone marrow- and adipose tissue-derived adult human mesenchymal stem cells. Biomed Mater Eng 2010; 20(3): 145-58.
[http://dx.doi.org/10.3233/BME-2010-0626] [PMID: 20930322]
[http://dx.doi.org/10.3233/BME-2010-0626] [PMID: 20930322]
[52]
Wang Y, Yang J, Li H, et al. Hypoxia promotes dopaminergic differentiation of mesenchymal stem cells and shows benefits for transplantation in a rat model of Parkinson’s disease. PLoS One 2013; 8(1): e54296
[http://dx.doi.org/10.1371/journal.pone.0054296] [PMID: 23342124]
[http://dx.doi.org/10.1371/journal.pone.0054296] [PMID: 23342124]
[53]
Zhuo Y, Wang L, Ge L, et al. Hypoxic Culture Promotes Dopaminergic-Neuronal Differentiation of Nasal Olfactory Mucosa Mesenchymal Stem Cells via Upregulation of Hypoxia-Inducible Factor-1α. Cell Transplant 2017; 26(8): 1452-61.
[http://dx.doi.org/10.1177/0963689717720291] [PMID: 28901191]
[http://dx.doi.org/10.1177/0963689717720291] [PMID: 28901191]
[54]
Chung DJ, Wong A, Hayashi K, Yellowley CE. Effect of hypoxia on generation of neurospheres from adipose tissue-derived canine mesenchymal stromal cells. Vet J 2014; 199(1): 123-30.
[http://dx.doi.org/10.1016/j.tvjl.2013.10.020] [PMID: 24252224]
[http://dx.doi.org/10.1016/j.tvjl.2013.10.020] [PMID: 24252224]
[55]
Pacary E, Legros H, Valable S, et al. Synergistic effects of CoCl(2) and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells. J Cell Sci 2006; 119(Pt 13): 2667-78.
[http://dx.doi.org/10.1242/jcs.03004] [PMID: 16772336]
[http://dx.doi.org/10.1242/jcs.03004] [PMID: 16772336]
[56]
Rochefort GY, Delorme B, Lopez A, et al. Multipotential mesenchymal stem cells are mobilized into peripheral blood by hypoxia. Stem Cells 2006; 24(10): 2202-8.
[http://dx.doi.org/10.1634/stemcells.2006-0164] [PMID: 16778152]
[http://dx.doi.org/10.1634/stemcells.2006-0164] [PMID: 16778152]
[57]
Fan Y, Wang L, Liu C, et al. Local renin-angiotensin system regulates hypoxia-induced vascular endothelial growth factor synthesis in mesenchymal stem cells. Int J Clin Exp Pathol 2015; 8(3): 2505-14.
[PMID: 26045756]
[PMID: 26045756]
[58]
Xing Y, Hou J, Guo T, et al. microRNA-378 promotes mesenchymal stem cell survival and vascularization under hypoxic-ischemic conditions in vitro. Stem Cell Res Ther 2014; 5(6): 130.
[http://dx.doi.org/10.1186/scrt520] [PMID: 25418617]
[http://dx.doi.org/10.1186/scrt520] [PMID: 25418617]
[59]
Sheng L, Mao X, Yu Q, Yu D. Effect of the PI3K/AKT signaling pathway on hypoxia-induced proliferation and differentiation of bone marrow-derived mesenchymal stem cells. Exp Ther Med 2017; 13(1): 55-62.
[http://dx.doi.org/10.3892/etm.2016.3917] [PMID: 28123468]
[http://dx.doi.org/10.3892/etm.2016.3917] [PMID: 28123468]
[60]
Liu C, Tsai AL, Li PC, Huang CW, Wu CC. Endothelial differentiation of bone marrow mesenchyme stem cells applicable to hypoxia and increased migration through Akt and NFκB signals. Stem Cell Res Ther 2017; 8(1): 29.
[http://dx.doi.org/10.1186/s13287-017-0470-0] [PMID: 28173835]
[http://dx.doi.org/10.1186/s13287-017-0470-0] [PMID: 28173835]
[61]
Ni L, Liu X, Sochacki KR, et al. Effects of hypoxia on differentiation from human placenta-derived mesenchymal stem cells to nucleus pulposus-like cells. Spine J 2014; 14(10): 2451-8.
[http://dx.doi.org/10.1016/j.spinee.2014.03.028] [PMID: 24662208]
[http://dx.doi.org/10.1016/j.spinee.2014.03.028] [PMID: 24662208]
[62]
Cui X, Liu M, Wang J, Zhou Y, Xiang Q. Electrospun scaffold containing TGF-β1 promotes human mesenchymal stem cell differentiation towards a nucleus pulposus-like phenotype under hypoxia. IET Nanobiotechnol 2015; 9(2): 76-84.
[http://dx.doi.org/10.1049/iet-nbt.2014.0006] [PMID: 25829173]
[http://dx.doi.org/10.1049/iet-nbt.2014.0006] [PMID: 25829173]
[63]
Feng G, Jin X, Hu J, et al. Effects of hypoxias and scaffold architecture on rabbit mesenchymal stem cell differentiation towards a nucleus pulposus-like phenotype. Biomaterials 2011; 32(32): 8182-9.
[http://dx.doi.org/10.1016/j.biomaterials.2011.07.049] [PMID: 21839506]
[http://dx.doi.org/10.1016/j.biomaterials.2011.07.049] [PMID: 21839506]
[64]
Fang Z, Yang Q, Luo W, et al. Differentiation of GFP-Bcl-2-engineered mesenchymal stem cells towards a nucleus pulposus-like phenotype under hypoxia in vitro. Biochem Biophys Res Commun 2013; 432(3): 444-50.
[http://dx.doi.org/10.1016/j.bbrc.2013.01.127] [PMID: 23416353]
[http://dx.doi.org/10.1016/j.bbrc.2013.01.127] [PMID: 23416353]
[65]
Stoyanov JV, Gantenbein-Ritter B, Bertolo A, et al. Role of hypoxia and growth and differentiation factor-5 on differentiation of human mesenchymal stem cells towards intervertebral nucleus pulposus-like cells. Eur Cell Mater 2011; 21: 533-47.
[http://dx.doi.org/10.22203/eCM.v021a40] [PMID: 21710444]
[http://dx.doi.org/10.22203/eCM.v021a40] [PMID: 21710444]
[66]
Sun B, Meng XH, Liu R, Yan S, Xiao ZD. Mechanism study for hypoxia induced differentiation of insulin-producing cells from umbilical cord blood-derived mesenchymal stem cells. Biochem Biophys Res Commun 2015; 466(3): 444-9.
[http://dx.doi.org/10.1016/j.bbrc.2015.09.047] [PMID: 26392316]
[http://dx.doi.org/10.1016/j.bbrc.2015.09.047] [PMID: 26392316]
[67]
Li Y, Shi X, Yang L, et al. Hypoxia promotes the skewed differentiation of umbilical cord mesenchymal stem cells toward type II alveolar epithelial cells by regulating microRNA-145. Gene 2017; 630: 68-75.
[http://dx.doi.org/10.1016/j.gene.2017.08.006] [PMID: 28789953]
[http://dx.doi.org/10.1016/j.gene.2017.08.006] [PMID: 28789953]
[68]
Chen B, Chen X, Liu C, Li J, Liu F, Huang Y. Co-expression of Akt1 and Wnt11 promotes the proliferation and cardiac differentiation of mesenchymal stem cells and attenuates hypoxia/reoxygenation-induced cardiomyocyte apoptosis. Biomed Pharmacother 2018; 108: 508-14.
[http://dx.doi.org/10.1016/j.biopha.2018.09.047] [PMID: 30243083]
[http://dx.doi.org/10.1016/j.biopha.2018.09.047] [PMID: 30243083]
[69]
Chen O, Wu M, Jiang L. The Effect of Hypoxic Preconditioning on Induced Schwann Cells under Hypoxic Conditions. PLoS One 2015; 10(10): e0141201
[http://dx.doi.org/10.1371/journal.pone.0141201] [PMID: 26509259]
[http://dx.doi.org/10.1371/journal.pone.0141201] [PMID: 26509259]
[70]
Weston M. Stem cell-transplantation therapy for adrenoleukodystrophy: current perspectives. J Neurorestoratol 2017; 2017(5): 5-19.
[71]
Zhijian C, Xijing H. Anti-inflammatory effect of stem cells against spinal cord injury via regulating macrophage polarization. J Neurorestoratol 2017; 2017(5): 31-8.
[72]
Gonzalez FJ, Xie C, Jiang C. The role of hypoxia-inducible factors in metabolic diseases. Nat Rev Endocrinol 2018; 15(1): 21-32.
[http://dx.doi.org/10.1038/s41574-018-0096-z] [PMID: 30275460]
[http://dx.doi.org/10.1038/s41574-018-0096-z] [PMID: 30275460]
[73]
Xu W, Xu R, Li Z, Wang Y, Hu R. Hypoxia changes chemotaxis behaviour of mesenchymal stem cells via HIF-1α signalling. J Cell Mol Med 2019; 23(3): 1899-907.
[http://dx.doi.org/10.1111/jcmm.14091] [PMID: 30628201]
[http://dx.doi.org/10.1111/jcmm.14091] [PMID: 30628201]
[74]
Holmquist-Mengelbier L, Fredlund E, Löfstedt T, et al. Recruitment of HIF-1α and HIF-2α to common target genes is differentially regulated in neuroblastoma: HIF-2α promotes an aggressive phenotype. Cancer Cell 2006; 10(5): 413-23.
[http://dx.doi.org/10.1016/j.ccr.2006.08.026] [PMID: 17097563]
[http://dx.doi.org/10.1016/j.ccr.2006.08.026] [PMID: 17097563]
[75]
Koh MY, Lemos R Jr, Liu X, Powis G. The hypoxia-associated factor switches cells from HIF-1α- to HIF-2α-dependent signaling promoting stem cell characteristics, aggressive tumor growth and invasion. Cancer Res 2011; 71(11): 4015-27.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-4142] [PMID: 21512133]
[http://dx.doi.org/10.1158/0008-5472.CAN-10-4142] [PMID: 21512133]
[76]
Makino Y, Cao R, Svensson K, et al. Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Nature 2001; 414(6863): 550-4.
[http://dx.doi.org/10.1038/35107085] [PMID: 11734856]
[http://dx.doi.org/10.1038/35107085] [PMID: 11734856]
[77]
Mylotte LA, Duffy AM, Murphy M, et al. Metabolic flexibility permits mesenchymal stem cell survival in an ischemic environment. Stem Cells 2008; 26(5): 1325-36.
[http://dx.doi.org/10.1634/stemcells.2007-1072] [PMID: 18308942]
[http://dx.doi.org/10.1634/stemcells.2007-1072] [PMID: 18308942]
[78]
Drela K, Sarnowska A, Siedlecka P, et al. Low oxygen atmosphere facilitates proliferation and maintains undifferentiated state of umbilical cord mesenchymal stem cells in an hypoxia inducible factor-dependent manner. Cytotherapy 2014; 16(7): 881-92.
[http://dx.doi.org/10.1016/j.jcyt.2014.02.009] [PMID: 24726658]
[http://dx.doi.org/10.1016/j.jcyt.2014.02.009] [PMID: 24726658]
[79]
Gu Q, Gu Y, Shi Q, Yang H. Hypoxia Promotes Osteogenesis of Human Placental-Derived Mesenchymal Stem Cells. Tohoku J Exp Med 2016; 239(4): 287-96.
[http://dx.doi.org/10.1620/tjem.239.287] [PMID: 27477937]
[http://dx.doi.org/10.1620/tjem.239.287] [PMID: 27477937]
[80]
Binder BY, Sagun JE, Leach JK. Reduced serum and hypoxic culture conditions enhance the osteogenic potential of human mesenchymal stem cells. Stem Cell Rev Rep 2015; 11(3): 387-93.
[http://dx.doi.org/10.1007/s12015-014-9555-7] [PMID: 25173881]
[http://dx.doi.org/10.1007/s12015-014-9555-7] [PMID: 25173881]
[81]
Ciapetti G, Granchi D, Fotia C, et al. Effects of hypoxia on osteogenic differentiation of mesenchymal stromal cells used as a cell therapy for avascular necrosis of the femoral head. Cytotherapy 2016; 18(9): 1087-99.
[http://dx.doi.org/10.1016/j.jcyt.2016.06.005] [PMID: 27421741]
[http://dx.doi.org/10.1016/j.jcyt.2016.06.005] [PMID: 27421741]
[82]
Ren H, Cao Y, Zhao Q, et al. Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions. Biochem Biophys Res Commun 2006; 347(1): 12-21.
[http://dx.doi.org/10.1016/j.bbrc.2006.05.169] [PMID: 16814746]
[http://dx.doi.org/10.1016/j.bbrc.2006.05.169] [PMID: 16814746]
[83]
Potier E, Ferreira E, Andriamanalijaona R, et al. Hypoxia affects mesenchymal stromal cell osteogenic differentiation and angiogenic factor expression. Bone 2007; 40(4): 1078-87.
[http://dx.doi.org/10.1016/j.bone.2006.11.024] [PMID: 17276151]
[http://dx.doi.org/10.1016/j.bone.2006.11.024] [PMID: 17276151]
[84]
Zhang P, Ha N, Dai Q, Zhou S, Yu C, Jiang L. Hypoxia suppresses osteogenesis of bone mesenchymal stem cells via the extracellular signal‑regulated 1/2 and p38‑mitogen activated protein kinase signaling pathways. Mol Med Rep 2017; 16(4): 5515-22.
[http://dx.doi.org/10.3892/mmr.2017.7276] [PMID: 28849067]
[http://dx.doi.org/10.3892/mmr.2017.7276] [PMID: 28849067]
[85]
Zhang Y, Marsboom G, Toth PT, Rehman J. Mitochondrial respiration regulates adipogenic differentiation of human mesenchymal stem cells. PLoS One 2013; 8(10): e77077
[http://dx.doi.org/10.1371/journal.pone.0077077] [PMID: 24204740]
[http://dx.doi.org/10.1371/journal.pone.0077077] [PMID: 24204740]
[86]
Ding H, Chen S, Yin JH, et al. Continuous hypoxia regulates the osteogenic potential of mesenchymal stem cells in a time-dependent manner. Mol Med Rep 2014; 10(4): 2184-90.
[http://dx.doi.org/10.3892/mmr.2014.2451] [PMID: 25109357]
[http://dx.doi.org/10.3892/mmr.2014.2451] [PMID: 25109357]
[87]
Markway BD, Tan GK, Brooke G, Hudson JE, Cooper-White JJ, Doran MR. Enhanced chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells in low oxygen environment micropellet cultures. Cell Transplant 2010; 19(1): 29-42.
[http://dx.doi.org/10.3727/096368909X478560] [PMID: 19878627]
[http://dx.doi.org/10.3727/096368909X478560] [PMID: 19878627]
[88]
Gómez-Leduc T, Desancé M, Hervieu M, et al. Hypoxia Is a Critical Parameter for Chondrogenic Differentiation of Human Umbilical Cord Blood Mesenchymal Stem Cells in Type I/III Collagen Sponges. Int J Mol Sci 2017; 18(9): E1933
[http://dx.doi.org/10.3390/ijms18091933] [PMID: 28885597]
[http://dx.doi.org/10.3390/ijms18091933] [PMID: 28885597]
Article Metrics
48
6