Skip to main content
SpringerLink
Log in

In vitro augmentation of mesenchymal stem cells viability in stressful microenvironments

In vitro augmentation of mesenchymal stem cells viability

  • Mini Review
  • Published:
Cell Stress and Chaperones Aims and scope

Abstract

Mesenchymal stem cells (MSCs) are under intensive investigation for use in cell-based therapies because their differentiation abilities, immunomodulatory effects, and homing properties offer potential for significantly augmenting regenerative capacity of many tissues. Nevertheless, major impediments to their therapeutic application, such as low proliferation and survival rates remain as obstacles to broad clinical use of MSCs. Another major challenge to evolution of MSC-based therapies is functional degradation of these cells as a result of their exposure to oxidative stressors during isolation. Indeed, oxidative stress-mediated MSC depletion occurs due to inflammatory processes associated with chemotherapy, radiotherapy, and expression of pro-apoptotic factors, and the microenvironment of damaged tissue in patients receiving MSC therapy is typically therapeutic not favorable to their survival. For this reason, any strategies that enhance the viability and proliferative capacity of MSCs associated with their therapeutic use are of great value. Here, recent strategies used by various researchers to improve MSC allograft function are reviewed, with particular focus on in vitro conditioning of MSCs in preparation for clinical application. Preconditioning, genetic manipulation, and optimization of MSC culture conditions are some examples of the methodologies described in the present article, along with novel strategies such as treatment of MSCs with secretome and MSC-derived microvesicles. This topic material is likely to find value as a guide for both research and clinical use of MSC allografts and for improvement of the value that use of these cells brings to health care.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Al-Nbaheen M et al (2013) Human stromal (mesenchymal) stem cells from bone marrow, adipose tissue and skin exhibit differences in molecular phenotype and differentiation potential. Stem Cell Rev Rep 9:32–43

    CAS  Google Scholar 

  • Amiri F, Halabian R, Dehgan Harati M, Bahadori M, Mehdipour A, Mohammadi Roushandeh A, Habibi Roudkenar M (2014a) Positive selection of Wharton’s jelly-derived CD105+ cells by MACS technique and their subsequent cultivation under suspension culture condition: a simple, versatile culturing method to enhance the multipotentiality of mesenchymal stem cells Hematology

  • Amiri F, Halabian R, Salimian M, Shokrgozar MA, Soleimani M, Jahanian-Najafabadi A, Roudkenar MH (2014b) Induction of multipotency in umbilical cord-derived mesenchymal stem cells cultivated under suspension conditions Cell Stress and Chaperones:1–10

  • Angoulvant D, Ivanes F, Ferrera R, Matthews PG, Nataf S, Ovize M (2011) Mesenchymal stem cell conditioned media attenuates in vitro and ex vivo myocardial reperfusion injury. J Heart Lung Transplant 30:95–102

    PubMed  Google Scholar 

  • Arno AI, Amini-Nik S, Blit PH, Al-Shehab M, Belo C, Herer E, Jeschke MG (2014) Effect of human Wharton’s jelly mesenchymal stem cell paracrine signaling on keloid fibroblasts stem cells translational medicine:sctm. 2013–0120

  • Asakura S, Hurley RW, Skorstengaard K, Ohkubo I, Mosher DF (1992) Inhibition of cell adhesion by high molecular weight kininogen. J Cell Biol 116:465–476

    CAS  PubMed  Google Scholar 

  • Baglio SR, Pegtel DM, Baldini N (2012) Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy Frontiers in physiology 3

  • Bahmani B, Roudkenar MH, Halabian R, Jahanian-Najafabadi A, Amiri F, Jalili MA (2014) Lipocalin 2 decreases senescence of bone marrow-derived mesenchymal stem cells under sub-lethal doses of oxidative stress Cell Stress and Chaperones:1–9

  • Baker BM, Chen CS (2012) Deconstructing the third dimension—how 3D culture microenvironments alter cellular cues. J Cell Sci 125:3015–3024

    PubMed Central  CAS  PubMed  Google Scholar 

  • Banerjee M, Bhonde RR (2006) Application of hanging drop technique for stem cell differentiation and cytotoxicity studies. Cytotechnology 51:1–5

    PubMed Central  PubMed  Google Scholar 

  • Bao C, Guo J, Lin G, Hu M, Hu Z (2008) TNFR gene-modified mesenchymal stem cells attenuate inflammation and cardiac dysfunction following MI. Scand Cardiovasc J 42:56–62

    CAS  PubMed  Google Scholar 

  • Barboza CAG, Ginani F, Soares DM, Henriques ÁCG, Freitas RdA (2014) Low-level laser irradiation induces in vitro proliferation of mesenchymal stem cells Einstein (São Paulo) 12:75–81

  • Bartosh TJ et al (2010) Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties. Proc Natl Acad Sci 107:13724–13729

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bieback K, Hecker A, Kocaömer A, Lannert H, Schallmoser K, Strunk D, Klüter H (2009) Human alternatives to fetal bovine serum for the expansion of mesenchymal stromal cells from bone marrow. Stem Cells 27:2331–2341

    CAS  PubMed  Google Scholar 

  • Biffi A et al (2013) Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 341:1233158

    PubMed  Google Scholar 

  • Bizzarri A, Koehler H, Cajlakovic M, Pasic A, Schaupp L, Klimant I, Ribitsch V (2006) Continuous oxygen monitoring in subcutaneous adipose tissue using microdialysis. Anal Chim Acta 573:48–56

    PubMed  Google Scholar 

  • Boopathy AV, Pendergrass KD, Che PL, Yoon Y-S, Davis ME (2013) Oxidative stress-induced Notch1 signaling promotes cardiogenic gene expression in mesenchymal stem cells. Stem Cell Res & therapy 4:1–15

    Google Scholar 

  • Boyette LB, Tuan RS (2014) Adult stem cells and diseases of aging. J Clin Med 3:88–134

    PubMed Central  CAS  PubMed  Google Scholar 

  • Brind’Amour K (2012) Ethics and induced pluripotent stem cells embryo project encyclopedia

  • Bruno S et al (2009) Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J Am Soc Nephrol 20:1053–1067

    PubMed Central  CAS  PubMed  Google Scholar 

  • Burova E, Borodkina A, Shatrova A, Nikolsky N (2013) Sublethal oxidative stress induces the premature senescence of human mesenchymal stem cells derived from endometrium oxidative medicine and cellular longevity 2013

  • Cai J et al. (2013a) Generation of tooth-like structures from integration-free human urine induced pluripotent stem cells Cell Regeneration 2

  • Cai T-Y, Zhu W, Chen X-S, Zhou S-Y, Jia L-S, Sun Y-Q (2013b) Fibroblast growth factor 2 induces mesenchymal stem cells to differentiate into tenocytes through the MAPK pathway. Molecular medicine reports 8:1323–1328

    CAS  PubMed  Google Scholar 

  • Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L (2010) Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int 78:838–848

    CAS  PubMed  Google Scholar 

  • Camussi G, Deregibus MC, Cantaluppi V (2013) Role of stem-cell-derived microvesicles in the paracrine action of stem cells. Biochem Soc Trans 41:283–287

    CAS  PubMed  Google Scholar 

  • Cantinieaux D et al (2013) Conditioned medium from bone marrow-derived mesenchymal stem cells improves recovery after spinal cord injury in rats: an original strategy to avoid cell transplantation. PLoS One 8:e69515

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cardoso TC et al (2012) Isolation and characterization of Wharton’s jelly-derived multipotent mesenchymal stromal cells obtained from bovine umbilical cord and maintained in a defined serum-free three-dimensional system. BMC Biotechnol 12:18

    PubMed Central  CAS  PubMed  Google Scholar 

  • Carpentier B, Layrolle P, Legallais C (2011) Bioreactors for bone tissue engineering. Int J Artif Organs 34:259–270

    CAS  PubMed  Google Scholar 

  • Chen H, J. A. W (2014) GW25-e1653 SIRT1 enhances therapeutic efficacy of aged mesenchymal stem cells in rat myocardial infarction via lightening MSCs aging and heightening stress resistance. J Am Coll Cardiol 64

  • Chen M et al (2012a) Serum starvation induced cell cycle synchronization facilitates human somatic cells reprogramming. PLoS One 7:e28203

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chen X-D et al (2012b) Characterization of bone marrow derived mesenchymal stem cells in suspension. Stem Cell Res Ther 3:40

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cheng N-C, Wang S, Young TH (2012) The influence of spheroid formation of human adipose-derived stem cells on chitosan films on stemness and differentiation capabilities. Biogeosciences 33:1748–1758

    CAS  Google Scholar 

  • Choi MR, Kim SH, Ohn T, Jung KH, Chai YG (2014) Resveratrol relieves hydrogen peroxide-induced premature senescence associated with SIRT1 in human mesenchymal. Stem cells Mol & Cell Toxicol 10:29–39

    CAS  Google Scholar 

  • Choo KB et al (2014) Oxidative stress-induced premature senescence in Wharton’s jelly-derived mesenchymal stem cells. J Med Sci 11:1201

    Google Scholar 

  • Choudhery MS, Khan M, Mahmood R, Mehmood A, Khan SN, Riazuddin S (2012a) Bone marrow derived mesenchymal stem cells from aged mice have reduced wound healing, angiogenesis, proliferation and anti‐apoptosis capabilities. Cell Biol Int 36:747–753

    CAS  PubMed  Google Scholar 

  • Choudhery MS et al (2012b) Mesenchymal stem cells conditioned with glucose depletion augments their ability to repair‐infarcted myocardium. J Cell Mol Med 16:2518–2529

    CAS  PubMed  Google Scholar 

  • Choudhery MS, Badowski M, Muise A, Harris DT (2013) Comparison of human mesenchymal stem cells derived from adipose and cord tissue. Cytotherapy 15:330–343

    CAS  PubMed  Google Scholar 

  • Collino F et al (2010) Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS One 5:e11803

    PubMed Central  PubMed  Google Scholar 

  • Cramer C et al (2010) Persistent high glucose concentrations alter the regenerative potential of mesenchymal stem cells. Stem Cells Dev 19:1875–1884

    CAS  PubMed  Google Scholar 

  • Cui H, Kong Y, Zhang H (2011) Oxidative stress, mitochondrial dysfunction, and aging Journal of signal transduction 2012

  • Devine SM, Cobbs C, Jennings M, Bartholomew A, Hoffman R (2003) Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood 101:2999–3001

    CAS  PubMed  Google Scholar 

  • Dominici M et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. Int Society for Cellular Therapy position statement Cytotherapy 8:315–317

    CAS  Google Scholar 

  • Donzelli E et al (2007) Mesenchymal stem cells cultured on a collagen scaffold: in vitro osteogenic differentiation. Arch Oral Biol 52:64–73

    CAS  PubMed  Google Scholar 

  • Drela K et al. (2014) Low oxygen atmosphere facilitates proliferation and maintains undifferentiated state of umbilical cord mesenchymal stem cells in an hypoxia inducible factor-dependent manner Cytotherapy

  • Ehninger A, Trumpp A (2011) The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in. J Exp Med 208:421–428

    PubMed Central  CAS  PubMed  Google Scholar 

  • Eitan Y, Sarig U, Dahan N, Machluf M (2009) A cellular cardiac extracellular matrix as a scaffold for tissue engineering: in vitro cell support, remodeling, and biocompatibility tissue engineering part C. Methods 16:671–683

    Google Scholar 

  • El-Amin S, Lu H, Khan Y, Burems J, Mitchell J, Tuan R, Laurencin C (2003) Extracellular matrix production by human osteoblasts cultured on biodegradable polymers applicable for tissue engineering. Biomaterials 24:1213–1221

    CAS  PubMed  Google Scholar 

  • Estrada J et al. (2013) Human mesenchymal stem cell-replicative senescence and oxidative stress are closely linked to aneuploidy Cell death & disease 4:e691

  • Fehrer C et al (2007) Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan. Aging cell 6:745–757

    CAS  PubMed  Google Scholar 

  • Fischer B, Bavister B (1993) Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits. J Reprod Fertil 99:673–679

    CAS  PubMed  Google Scholar 

  • Fossett E, Khan W (2012) Optimising human mesenchymal stem cell numbers for clinical application: a literature review Stem cells international 2012

  • Francois S, Mouiseddine M, Allenet-Lepage B, Voswinkel J, Douay L, Benderitter M, Chapel A (2013) Human mesenchymal stem cells provide protection against radiation-induced liver injury by antioxidative process, vasculature protection, hepatocyte differentiation, and trophic effects BioMed research international 2013

  • Frith JE, Thomson B, Genever PG (2009) Dynamic three-dimensional culture methods enhance mesenchymal stem cell properties and increase therapeutic potential tissue engineering part C. Methods 16:735–749

    Google Scholar 

  • Fu W-L et al (2011) Proliferation and apoptosis property of mesenchymal stem cells derived from peripheral blood under the culture conditions of hypoxia and serum deprivation. Chinese Medical Journal-Beijing 124:3959

    CAS  Google Scholar 

  • Gao F, He T, Wang H, Yu S, Yi D, Liu W, Cai Z (2007) A promising strategy for the treatment of ischemic heart disease: mesenchymal stem cell-mediated vascular endothelial growth factor gene transfer in rats. Can J Cardiol 23:891–898

    PubMed Central  PubMed  Google Scholar 

  • Garbern JC, Lee RT (2013) Cardiac stem cell therapy and the promise of heart regeneration cell. Stem Cell 12:689–698

    CAS  Google Scholar 

  • Gharibi B, Farzadi S, Ghuman M, Hughes FJ (2014) Inhibition of Akt/mTOR attenuates age‐related changes in mesenchymal stem cells STEM CELLS

  • Godara P, McFarland CD, Nordon RE (2008) Design of bioreactors for mesenchymal stem cell tissue engineering. J Chem Technol Biotechnol 83:408–420

    CAS  Google Scholar 

  • Greco SJ, Rameshwar P (2012) Mesenchymal stem cells in drug/gene delivery: implications for cell therapy. Ther Deliv 3:997–1004

    CAS  PubMed  Google Scholar 

  • Haider HK, Ashraf M (2008) Strategies to promote donor cell survival: combining preconditioning approach with stem cell transplantation. J Mol Cell Cardiol 45:554–566

    PubMed Central  CAS  PubMed  Google Scholar 

  • Haider KH, Jiang S, Idris NM, Ashraf M (2008) IGF-1-overexpressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1alpha/CXCR4 signaling to promote myocardial repair. Circ Res 103:1300–8

    CAS  PubMed  Google Scholar 

  • Haines DD, Juhasz B, Tosaki A (2013) Management of multicellular senescence and oxidative stress. J Cell Mol Med 17:936–957

    PubMed Central  PubMed  Google Scholar 

  • Halabian R, Tehrani HA, Jahanian-Najafabadi A, Roudkenar MH (2013) Lipocalin-2-mediated upregulation of various antioxidants and growth factors protects bone marrow-derived mesenchymal stem cells against unfavorable microenvironments. Cell Stress and Chaperones 18:785–800

    PubMed Central  CAS  PubMed  Google Scholar 

  • Halme DG, Kessler DA (2006) FDA regulation of stem-cell-based therapies. N Engl J Med 355:1730–1735

    CAS  PubMed  Google Scholar 

  • Hamedi-Asl P et al (2012) Adenovirus-mediated expression of the HO-1 protein within MSCs decreased cytotoxicity and inhibited apoptosis induced by oxidative stresses. Cell Stress and Chaperones 17:181–190

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hammoud M et al (2012) Combination of low O2 concentration and mesenchymal stromal cells during culture of cord blood CD34+ cells improves the maintenance and proliferative capacity of hematopoietic stem cells. J Cell Physiol 227:2750–2758

    CAS  PubMed  Google Scholar 

  • Han J, Mistriotis P, Lei P, Wang D, Liu S, Andreadis ST (2012) Nanog reverses the effects of organismal aging on mesenchymal stem cell proliferation and myogenic differentiation potential. Stem Cells 30:2746–2759

    PubMed Central  CAS  PubMed  Google Scholar 

  • Han Q, Fan L, Heng BC, Zigang GE (2013) Apoptosis and metabolism of mesenchymal stem cells during chondrogenic differentiation in vitro. Int J Tissue Regen 4:61–64

    Google Scholar 

  • Han S-M et al. (2014) Enhanced proliferation and differentiation of Oct4-and Sox2-overexpressing human adipose tissue mesenchymal stem cells Experimental & molecular medicine 46:e101

  • Hass R, Kasper C, Böhm S, Jacobs R (2011) Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal 9:12

    PubMed Central  CAS  PubMed  Google Scholar 

  • He A, Jiang Y, Gui C, Sun Y, Li J, Wang JA (2009) The antiapoptotic effect of mesenchymal stem cell transplantation on ischemic myocardium is enhanced by anoxic preconditioning. Can J Cardiol 25:353–358

    PubMed Central  CAS  PubMed  Google Scholar 

  • Herberts CA, Kwa M, Hermsen H (2011) Risk factors in the development of stem cell therapy. J Transl Med 9:29

    PubMed Central  PubMed  Google Scholar 

  • Herrmann JL, Wang Y, Abarbanell AM, Weil BR, Tan J, Meldrum DR (2010) Preconditioning mesenchymal stem cells with transforming growth factor-alpha improves mesenchymal stem cell-mediated cardioprotection. Shock 33:24–30

    CAS  PubMed  Google Scholar 

  • Higuchi O, Okabe M, Yoshida T, Fathy M, Saito S, Miyawaki T, Nikaido T (2012) Stemness of human Wharton’s jelly mesenchymal cells is maintained by floating cultivation cellular reprogramming. Formerly “Cloning and Stem Cells” 14:448–455

    CAS  Google Scholar 

  • Hodgkinson CP, Gomez JA, Mirotsou M, Dzau VJ (2010) Genetic engineering of mesenchymal stem cells and its application in human disease therapy. Hum Gene Ther 21:1513–1526

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56:549–580

    CAS  PubMed  Google Scholar 

  • Hu X, Yu SP, Fraser JL, Lu Z, Ogle ME, Wang JA, Wei L (2008) Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. J Thorac Cardiovasc Surg 135:799–808

    CAS  PubMed  Google Scholar 

  • Huebsch N et al (2010) Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate. Nat Mater 9:518–526

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hung SC, Pochampally RR, Chen SC, Hsu SC, Prockop DJ (2007) Angiogenic effects of human multipotent stromal cell conditioned medium activate the PI3K‐Akt pathway in hypoxic endothelial cells to inhibit apoptosis. Increase Survival, and Stimulate Angiogenesis Stem Cells 25:2363–2370

    CAS  Google Scholar 

  • Ishihara K, Ishikawa E, Iwasaki Y, Nakabayashi N (1999) Inhibition of fibroblast cell adhesion on substrate by coating with 2-methacryloyloxyethyl phosphorylcholine polymers. J Biomater Science Polymer Edition 10:1047–1061

    CAS  Google Scholar 

  • Ito D, Yagi T, Suzuki N (2013) [Progress in induced pluripotent stem cell research for age-related neurodegenerative diseases] Brain and nerve = Shinkei kenkyu no shinpo 65:283–288

  • Iwase T et al (2005) Comparison of angiogenic potency between mesenchymal stem cells and mononuclear cells in a rat model of hindlimb ischemia. Cardiovasc Res 66:543–551

    CAS  PubMed  Google Scholar 

  • J Salgado A, L Reis R, Sousa N, M Gimble J (2010) Adipose tissue derived stem cells secretome: soluble factors and their roles in regenerative medicine Current stem cell research & therapy 5:103–110

  • Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461:1071–1078

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jäderstad J, Brismar H, Herlenius E (2010) Hypoxic preconditioning increases gap-junctional graft and host communication. Neuroreport 21:1126–1132

    PubMed  Google Scholar 

  • Jin HJ et al (2013) Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. Int J Mol Sci 14:17986–18001

    PubMed Central  PubMed  Google Scholar 

  • Jones DL, Wagers AJ (2008) No place like home: anatomy and function of the stem cell niche. Nature Reviews Molecular Cell Biology 9:11–21

    CAS  PubMed  Google Scholar 

  • Katsha AM, Ohkouchi S, Xin H, Kanehira M, Sun R, Nukiwa T, Saijo Y (2010) Paracrine factors of multipotent stromal cells ameliorate lung injury in an elastase-induced emphysema model. Mol Ther 19:196–203

    PubMed Central  PubMed  Google Scholar 

  • Kensler TW, Wakabayashi N, Biswal S (2007) Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 47:89–116

    CAS  PubMed  Google Scholar 

  • Khan M et al (2013) Preconditioning diabetic mesenchymal stem cells with myogenic medium increases their ability to repair diabetic heart. Stem Cell Res Ther 4:58

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kiani AA, Abdi J, Halabian R, Roudkenar MH, Amirizadeh N, Soleiman Soltanpour M, Kazemi A (2014) Over expression of HIF-1α in human mesenchymal stem cells increases their supportive functions for hematopoietic stem cells in an experimental co-culture model. Hematology 19:85–98

    CAS  PubMed  Google Scholar 

  • Knoepfler PS (2009) Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicine. Stem Cells 27:1050–1056

    PubMed Central  CAS  PubMed  Google Scholar 

  • Koliakos I, Tsagias N, Karagiannis V (2011) Mesenchymal cells isolation from Wharton’s jelly, in perspective to clinical applications. J Biol Res 16:194–201

    Google Scholar 

  • Krinner A, Hoffmann M, Loeffler M, Drasdo D, Galle J (2010) Individual fates of mesenchymal stem cells in vitro. BMC Syst Biol 4:73

    PubMed Central  PubMed  Google Scholar 

  • Kuhn LT et al (2013) Developmental-like bone regeneration by human embryonic stem cell-derived mesenchymal cells. Tissue Eng A 20:365–377

    Google Scholar 

  • Lavrentieva A, Majore I, Kasper C, Hass R (2010) Effects of hypoxic culture conditions on umbilical cord-derived human mesenchymal stem cells. Cell Commun Signal 8:18

    PubMed Central  PubMed  Google Scholar 

  • Law S, Chaudhuri S (2013) Mesenchymal stem cell and regenerative medicine: regeneration versus immunomodulatory challenges. American journal of stem cells 2:22

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lee J-M, Johnson JA (2004) An important role of Nrf2-ARE pathway in the cellular defense mechanism. BMB Rep 37:139–143

    CAS  Google Scholar 

  • Lee JS, Lee MO, Moon BH, Shim SH, Fornace AJ, Cha HJ (2009a) Senescent growth arrest in mesenchymal stem cells is bypassed by Wip1‐mediated downregulation of intrinsic stress signaling pathways. Stem Cells 27:1963–1975

    CAS  PubMed  Google Scholar 

  • Lee KA et al (2009b) Analysis of changes in the viability and gene expression profiles of human mesenchymal stromal cells over time. Cytotherapy 11:688–697

    CAS  PubMed  Google Scholar 

  • Lee MW, Jang IK, Yoo KH, Sung KW, Koo HH (2010) Stem and progenitor cells in human umbilical cord blood. Int J Hematol 92:45–51

    PubMed  Google Scholar 

  • Lee SK et al (2012) Phosphatase of regenerating liver‐3 promotes migration and invasion by upregulating matrix metalloproteinases‐7 in human colorectal cancer cells. Int J Cancer 131:E190–E203

    CAS  PubMed  Google Scholar 

  • Li Y, Lin F (2012) Mesenchymal stem cells are injured by complement after their contact with serum. Blood 120:3436–3443

    PubMed Central  CAS  PubMed  Google Scholar 

  • Li W et al (2007) Bcl‐2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells 25:2118–2127

    CAS  PubMed  Google Scholar 

  • Li S, Deng Y, Feng J, Ye W (2009) Oxidative preconditioning promotes bone marrow mesenchymal stem cells migration and prevents apoptosis. Cell Biol Int 33:411–418

    PubMed  Google Scholar 

  • Li Q, Wang Y, Deng Z (2013a) Pre-conditioned mesenchymal stem cells: a better way for cell-based therapy. Stem cell research & therapy 4:1–3

    Google Scholar 

  • Li X, Zhang Y, Qi G (2013b) Evaluation of isolation methods and culture conditions for rat bone marrow mesenchymal. Stem cells Cytotechnology 65:323–334

    CAS  Google Scholar 

  • Li D, Xu Y, Gao C, Zhai Y (2014) Adaptive protection against damage of preconditioning human umbilical cord-derived mesenchymal stem cells with hydrogen peroxide Genetics and molecular research: GMR 13

  • Lindenmair A et al (2012) Mesenchymal stem or stromal cells from amnion and umbilical cord tissue and their potential for clinical applications. Cells 1:1061–1088

    PubMed Central  CAS  PubMed  Google Scholar 

  • Linero I, Chaparro O (2014) Paracrine effect of mesenchymal stem cells derived from human adipose tissue in bone regeneration. PLoS One 9:e107001

    PubMed Central  PubMed  Google Scholar 

  • Liu TM, Wu YN, Guo XM, Hui JHP, Lee EH, Lim B (2009) Effects of ectopic Nanog and Oct4 overexpression on mesenchymal stem cells. Stem Cells Dev 18:1013–1022

    PubMed Central  CAS  PubMed  Google Scholar 

  • Liu H et al (2010) Hypoxic preconditioning advances CXCR4 and CXCR7 expression by activating HIF-1α in MSCs. Biochem Biophys Res Commun 401:509–515

    CAS  PubMed  Google Scholar 

  • Liu N et al (2011) Effects of transplantation with bone marrow-derived mesenchymal stem cells modified by Survivin on experimental stroke in rats. J Transl Med 9:105

    PubMed Central  CAS  PubMed  Google Scholar 

  • Liu TM et al (2012) Molecular basis of immortalization of human mesenchymal stem cells by combination of p53 knockdown and human telomerase reverse transcriptase overexpression. Stem Cells Dev 22:268–278

    PubMed Central  PubMed  Google Scholar 

  • Liu Y, Yang R, He Z, Gao W-Q (2013) Generation of functional organs from stem cells. Cell Regeneration 2:1

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lodi D, Iannitti T, Palmieri B (2011) Stem cells in clinical practice: applications and warnings. J Exp Clin Cancer Res 30:1–20

    Google Scholar 

  • Lu H, Li Y, Sheng Z, Wang Y (2012) Preconditioning of stem cells for the treatment of myocardial infarction. Chin Med J (Engl) 125:378–384

    CAS  Google Scholar 

  • Lund AW, Yener B, Stegemann JP, Plopper GE (2009) The natural and engineered 3D microenvironment as a regulatory cue during stem cell fate determination. Tissue Eng B Rev 15:371–380

    Google Scholar 

  • Luo Y et al. (2012) SURGICAL RESEARCH REVIEW Surgery

  • Ma T, Grayson WL, Fröhlich M, Vunjak‐Novakovic G (2009) Hypoxia and stem cell‐based engineering of mesenchymal tissues. Biotechnol Prog 25:32–42

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ma S, Xie N, Li W, Yuan B, Shi Y, Wang Y (2013) Immunobiology of mesenchymal stem cells Cell Death & Differentiation

  • Mahmood A, Wu H, Qu C, Mahmood S, Xiong Y, Kaplan D, Chopp M (2014) Down-regulation of Nogo-A by collagen scaffolds impregnated with bone marrow stromal cell treatment after traumatic brain injury promotes axonal regeneration in rats. Brain Res 1542:41–48

    CAS  PubMed  Google Scholar 

  • Malard F, Mohty M (2014) New insight for the diagnosis of gastrointestinal acute graft-versus-host disease mediators of inflammation 2014

  • Mansouri L, Xie Y, Rappolee DA (2012) Adaptive and pathogenic responses to stress by stem cells during development. Cells 1:1197–1224

    PubMed Central  CAS  PubMed  Google Scholar 

  • McGinley L, McMahon J, Strappe P, Barry F, Murphy M, O’Toole D, O’Brien T (2011) Lentiviral vector mediated modification of mesenchymal stem cells & enhanced survival in an in vitro model of ischaemia Stem Cell Res Ther 2:12

  • Meier RP et al (2013) Transplantation of mesenchymal stem cells for the treatment of liver diseases, is there enough evidence? Stem Cell Res 11(3):1348–64

    CAS  PubMed  Google Scholar 

  • Meinel L et al (2004) Bone tissue engineering using human mesenchymal stem cells: effects of scaffold material and medium flow. Ann Biomed Eng 32:112–122

    PubMed  Google Scholar 

  • Mennan C, Wright K, Bhattacharjee A, Balain B, Richardson J, Roberts S (2013) Isolation and characterisation of mesenchymal stem cells from different regions of the human umbilical cord BioMed research international 2013

  • Mertes H, Pennings G (2009) Cross-border research on human embryonic stem cells: legal and ethical considerations. Stem Cell Rev Rep 5:10–17

    Google Scholar 

  • Mirotsou M et al (2007) Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proc Natl Acad Sci 104:1643–1648

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mohammadzadeh M et al (2012) Nrf-2 overexpression in mesenchymal stem cells reduces oxidative stress-induced apoptosis and cytotoxicity. Cell Stress and Chaperones 17:553–565

    PubMed Central  CAS  PubMed  Google Scholar 

  • Moll G et al (2012) Are therapeutic human mesenchymal stromal cells compatible with human blood? Stem Cells 30(7):1565–74

  • Murphy MB, Moncivais K, Caplan AI (2013) Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine Experimental & molecular medicine 45:e54

  • Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136

    CAS  PubMed  Google Scholar 

  • Muturi HT, Dreesen JD, Nilewski E, Jastrow H, Giebel B, Ergun S, Singer BB (2013) Tumor and endothelial cell-derived microvesicles carry distinct CEACAMs and influence T-cell behavior. PLoS One 8:e74654

    PubMed Central  CAS  PubMed  Google Scholar 

  • Naderi‐Meshkin H, Bahrami AR, Bidkhori HR, Mirahmadi M, Ahmadiankia N (2014) Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy Cell biology international

  • Noiseux N et al (2004) Mesenchymal stem cells overexpressing Akt dramatically repair infarcted myocardium and improve cardiac function despite infrequent cellular fusion or differentiation. Mol Ther 14:840–850

    Google Scholar 

  • Nystedt J et al (2013) Cell surface structures influence lung clearance rate of systemically infused mesenchymal stromal cells. Stem Cells 31(2):317–26

    CAS  PubMed  Google Scholar 

  • Oh JS et al (2010) Hypoxia-preconditioned adipose tissue-derived mesenchymal stem cell increase the survival and gene expression of engineered neural stem cells in a spinal cord injury model. Neurosci Lett 472:215–219

    CAS  PubMed  Google Scholar 

  • Osugi M, Katagiri W, Yoshimi R, Inukai T, Hibi H, Ueda M (2012) Conditioned media from mesenchymal stem cells enhanced bone regeneration in rat calvarial bone defects. Tissue Eng A 18:1479–1489

    CAS  Google Scholar 

  • Paschos KA, Bird NC (2010) Liver regeneration and its impact on post-hepatectomy metastatic tumour recurrence. Anticancer Res 30:2161–2170

    PubMed  Google Scholar 

  • Pasha Z, Wang Y, Sheikh R, Zhang D, Zhao T, Ashraf M (2008) Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium. Cardiovasc Res 77:134–142

    CAS  PubMed  Google Scholar 

  • Pendergrass KD, Boopathy AV, Seshadri G, Maiellaro-Rafferty K, Che PL, Brown ME, Davis ME (2013) Acute preconditioning of cardiac progenitor cells with hydrogen peroxide enhances angiogenic pathways following ischemia-reperfusion injury. Stem Cells Dev 22:2414–2424

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pochampally RR, Smith JR, Ylostalo J, Prockop DJ (2004) Serum deprivation of human marrow stromal cells (hMSCs) selects for a subpopulation of early progenitor cells with enhanced expression of OCT-4 and other embryonic genes. Blood 103:1647–1652

    CAS  PubMed  Google Scholar 

  • Ponader S, Burger JA (2010) Modeling the marrow stem cell niche in vitro: is proximity the key to reproduction? Haematologica 95:e5

    PubMed Central  PubMed  Google Scholar 

  • Potier E, Ferreira E, Andriamanalijaona R, Pujol J-P, Oudina K, Logeart-Avramoglou D, Petite H (2007a) Hypoxia affects mesenchymal stromal cell osteogenic differentiation and angiogenic factor expression. Bone 40:1078–1087

    CAS  PubMed  Google Scholar 

  • Potier E, Ferreira E, Meunier A, Sedel L, Logeart-Avramoglou D, Petite H (2007b) Prolonged hypoxia concomitant with serum deprivation induces massive human mesenchymal stem cell death. Tissue Eng 13:1325–1331

    CAS  PubMed  Google Scholar 

  • Przybyla LM, Theunissen TW, Jaenisch R, Voldman J (2013) Matrix remodeling maintains embryonic stem cell self‐renewal by activating atat3 stem cells 31:1097–1106

  • Ramsey F (2011) A simple hanging drop cell culture protocol for generation of 3D spheroids Journal of Visualized Experiments

  • Ratajczak MZ (2011) The emerging role of microvesicles in cellular therapies for organ/tissue regeneration. Nephrol Dial Transplant 26:1453–1456

    PubMed  Google Scholar 

  • Ren H et al (2006) Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions. Biochem Biophys Res Commun 347:12–21

    CAS  PubMed  Google Scholar 

  • Ren G et al (2008) Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2:141–150

    CAS  PubMed  Google Scholar 

  • Ren G, Chen X, Dong F, Li W, Ren X, Zhang Y, Shi Y (2012) Concise review: mesenchymal stem cells and translational medicine: emerging issues. Stem cells translational medicine 1:51–58

    PubMed Central  CAS  PubMed  Google Scholar 

  • Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710

    CAS  PubMed  Google Scholar 

  • Ribeiro A et al (2013) Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells. Stem cell research & therapy 4:125

    Google Scholar 

  • Robey TE, Saiget MK, Reinecke H, Murry CE (2008) Systems approaches to preventing transplanted cell death in cardiac repair. J Mol Cell Cardiol 45:567–581

    PubMed Central  CAS  PubMed  Google Scholar 

  • Saunders A, Faiola F, Wang J (2013) Concise review: pursuing self‐renewal and pluripotency with the stem cell factor Nanog. Stem Cells 31:1227–1236

    PubMed Central  CAS  PubMed  Google Scholar 

  • Scadden DT (2006) The stem-cell niche as an entity of action. Nature 441:1075–1079

    CAS  PubMed  Google Scholar 

  • Scaglione S, Giannoni P, Quarto R (2011) Cell-biomaterial interactions reproducing a Niche ADVANCES IN REGENERATIVE MEDICINE:363

  • Seaberg RM, Van Der Kooy D (2003) Stem and progenitor cells: the premature desertion of rigorous definitions. Trends Neurosci 26(3):125–131

    CAS  PubMed  Google Scholar 

  • Shi W et al (2012) BDNF blended chitosan scaffolds for human umbilical cord MSC transplants in traumatic brain injury therapy. Biomaterials 33:3119–3126

    CAS  PubMed  Google Scholar 

  • Shtrichman R, Germanguz I, Eldor JI (2013) Induced pluripotent stem cells (iPSCs) derived from different cell sources and their potential for regenerative and personalized medicine. Current molecular medicine 13:792–805

    CAS  PubMed  Google Scholar 

  • Sikavitsas VI, Bancroft GN, Mikos AG (2002) Formation of three‐dimensional cell/polymer constructs for bone tissue engineering in a spinner flask and a rotating wall vessel bioreactor. J Biomed Mater Res 62:136–148

    CAS  PubMed  Google Scholar 

  • Singh P, Schwarzbauer JE (2012) Fibronectin and stem cell differentiation—lessons from chondrogenesis. J Cell Sci 125:3703–3712

    PubMed Central  CAS  PubMed  Google Scholar 

  • Song M et al (2013) The paracrine effects of mesenchymal stem cells stimulate the regeneration capacity of endogenous stem cells in the repair of a bladder-outlet-obstruction-induced overactive bladder. Stem Cells Dev 23:654–663

    PubMed  Google Scholar 

  • Stolzing A, Coleman N, Scutt A (2006) Glucose-induced replicative senescence in mesenchymal. Stem cells Rejuvenation research 9:31–35

    CAS  Google Scholar 

  • Stolzing A, Sellers D, Llewelyn O, Scutt A (2010) Diabetes induced changes in rat mesenchymal stem cells. Cells Tissues Organs 191:453–465

    CAS  PubMed  Google Scholar 

  • Stolzing A, Bauer E, Scutt A (2012) Suspension cultures of bone-marrow-derived mesenchymal stem cells: effects of donor age and glucose level. Stem Cells Dev 21:2718–2723

    CAS  PubMed  Google Scholar 

  • Sundin M, Ringdén O, Sundberg B, Nava S, Götherström C, Le Blanc K (2007) No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients. Haematologica 92:1208–1215

    CAS  PubMed  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    CAS  PubMed  Google Scholar 

  • Tan J et al (2012) Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial. JAMA 307:1169–1177

    CAS  PubMed  Google Scholar 

  • Tang J et al (2009a) Mesenchymal stem cells over-expressing SDF-1 promote angiogenesis and improve heart function in experimental myocardial infarction in rats. Eur J Cardiothorac Surg 36:644–650

    PubMed  Google Scholar 

  • Tang YL et al (2009b) Hypoxic preconditioning enhances the benefit of cardiac progenitor cell therapy for treatment of myocardial infarction by inducing CXCR4 expression. Circ Res 104:1209–1216

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tarte K et al (2010) Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation. Blood 115:1549–1553

    CAS  PubMed  Google Scholar 

  • Tetta C, Bruno S, Fonsato V, Deregibus MC, Camussi G (2011) The role of microvesicles in tissue repair. Organogenesis 7:105–115

    PubMed Central  PubMed  Google Scholar 

  • Toh WS, Lee EH, Cao T (2011) Potential of human embryonic stem cells in cartilage tissue engineering and regenerative medicine. Stem Cell Rev Rep 7:544–559

    Google Scholar 

  • Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult. Murine heart Circulation 105:93–98

    Google Scholar 

  • Tower J (2012) Stress and stem cells. WIREs Dev Biol 1:789–802

  • van den Akker F, de Jager S, Sluijter J (2013) Mesenchymal stem cell therapy for cardiac inflammation: immunomodulatory properties and the influence of toll-like receptors Mediators of inflammation 2013

  • Van Der Sanden B, Dhobb M, Berger F, Wion D (2010) Optimizing stem cell culture. J Cell Biochem 111:801–807

    PubMed  Google Scholar 

  • Wang JA et al (2008) Hypoxic preconditioning attenuates hypoxia/reoxygenation-induced apoptosis in mesenchymal stem cells. Acta Pharmacol Sin 29:74–82

  • Wang X et al (2009) Hsp20‐engineered mesenchymal stem cells Are resistant to oxidative stress via enhanced activation of Akt and increased secretion of growth factors. Stem Cells 27:3021–3031

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wang H et al (2013) Human mesenchymal stem cell transplantation changes proinflammatory gene expression through a nuclear factor‐κB‐dependent pathway in a rat focal cerebral ischemic model. J Neurosci Res 91(11):1440–9

    CAS  PubMed  Google Scholar 

  • Wang F et al. (2014a) Cytoprotective effect of melatonin against hypoxia/serum deprivation-induced cell death of bone marrow mesenchymal stem cells in vitro European journal of pharmacology

  • Wang X, Mei J, Liao C, Zhang L, Li M, Ding Q, Li S (2014b) Relationship between mesenchymal stem cells and liver cancer recurrence after liver transplantation in mice. Zhonghua yi xue za zhi 94:455–458

    CAS  PubMed  Google Scholar 

  • Wei H, Li Z, Hu S, Chen X, Cong X (2010) Apoptosis of mesenchymal stem cells induced by hydrogen peroxide concerns both endoplasmic reticulum stress and mitochondrial death pathway through regulation of caspases, p38 and JNK. J Cell Biochem 111:967–978

    CAS  PubMed  Google Scholar 

  • Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF (2013) Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacol Sin 34:747–754

    PubMed Central  CAS  PubMed  Google Scholar 

  • Whu SW, Tsai C-L, S-h H (2009) Evaluation of human bone marrow mesenchymal stem cells seeded into composite scaffolds and cultured in a dynamic culture system for neocartilage regeneration in vitro. J Med Biol Eng 29:52–59

    Google Scholar 

  • Willerth SM, Sakiyama-Elbert SE (2008) Combining stem cells and biomaterial scaffolds for constructing tissues and cell delivery

  • Wong RS (2011) Mesenchymal stem cells: angels or demons? BioMed Research International 2011

  • Wu Y-h, Wang J, Gong D-x G, H-y H, S-s ZH (2012) Effects of low-level laser irradiation on mesenchymal stem cell proliferation: a microarray analysis. Lasers Med Sci 27:509–519

  • Xu J et al (2012) High density lipoprotein protects mesenchymal stem cells from oxidative stress-induced apoptosis via activation of the PI3K/Akt pathway and suppression of reactive oxygen species. Int J Mol Sci 13:17104–17120

    PubMed Central  CAS  PubMed  Google Scholar 

  • Yang CC, Wang J, Chen SC, Hsieh YL (2013) Synergistic effects of low‐level laser and mesenchymal stem cells on functional recovery in rats with crushed sciatic nerves Journal of tissue engineering and regenerative medicine

  • Yeatts AB, Fisher JP (2011) Bone tissue engineering bioreactors: dynamic culture and the influence of shear stress. Bone 48:171–181

    CAS  PubMed  Google Scholar 

  • Yoon D, Kim Y, Jung H, Paik S, Lee J (2011) Importance of Sox2 in maintenance of cell proliferation and multipotency of mesenchymal stem cells in low‐density culture. Cell Prolif 44:428–440

    CAS  PubMed  Google Scholar 

  • Zhang M, Methot D, Poppa V, Fujio Y, Walsh K, Murry CE (2001) Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death strategies. J Mol Cell Cardiol 33:907–921

    CAS  PubMed  Google Scholar 

  • Zhang J et al (2012) Hydrogen peroxide preconditioning enhances the therapeutic efficacy of Wharton’s jelly mesenchymal stem cells after myocardial infarction. Chin Med J (Engl) 125:3472–3478

    CAS  Google Scholar 

  • Zhu W, Chen J, Cong X, Hu S, Chen X (2006) Hypoxia and serum deprivation‐induced apoptosis in mesenchymal stem cells. Stem Cells 24:416–425

    PubMed  Google Scholar 

  • Zimmerlin L, Park TS, Zambidis ET, Donnenberg VS, Donnenberg AD (2013) Mesenchymal stem cell secretome and regenerative therapy after cancer. Biochimie 95:2235–45

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran

    Fatemeh Amiri & Mehryar Habibi Roudkenar

  2. Department of Pharmaceutical Biotechnology, School of Pharmacy, Isfahan University of Medical Sciences and Health Services, Isfahan, Iran

    Ali Jahanian-Najafabadi

Authors
  1. Fatemeh Amiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ali Jahanian-Najafabadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mehryar Habibi Roudkenar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mehryar Habibi Roudkenar.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Amiri, F., Jahanian-Najafabadi, A. & Roudkenar, M.H. In vitro augmentation of mesenchymal stem cells viability in stressful microenvironments. Cell Stress and Chaperones 20, 237–251 (2015). https://doi.org/10.1007/s12192-014-0560-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12192-014-0560-1

Keywords

Search

Navigation