Advertisement

Translational Stroke Research

, Volume 4, Issue 1, pp 76–88 | Cite as

Preconditioning Strategy in Stem Cell Transplantation Therapy

  • Shan Ping Yu
  • Zheng Wei
  • Ling Wei
Review Article

Abstract

Stem cell transplantation therapy has emerged as a promising regenerative medicine for ischemic stroke and other neurodegenerative disorders. However, many issues and problems remain to be resolved before successful clinical applications of cell-based therapy. To this end, some recent investigations have sought to benefit from well-known mechanisms of ischemic/hypoxic preconditioning. Ischemic/hypoxic preconditioning activates endogenous defense mechanisms that show marked protective effects against multiple insults found in ischemic stroke and other acute attacks. As in many other cell types, a sublethal hypoxic exposure significantly increases the tolerance and regenerative properties of stem cells and progenitor cells. So far, a variety of preconditioning triggers have been tested on different stem cells and progenitor cells. Preconditioned stem cells and progenitors generally show much better cell survival, increased neuronal differentiation, enhanced paracrine effects leading to increased trophic support, and improved homing to the lesion site. Transplantation of preconditioned cells helps to suppress inflammatory factors and immune responses, and promote functional recovery. Although the preconditioning strategy in stem cell therapy is still an emerging research area, accumulating information from reports over the last few years already indicates it as an attractive, if not essential, prerequisite for transplanted cells. It is expected that stem cell preconditioning and its clinical applications will attract more attention in both the basic research field of preconditioning as well as in the field of stem cell translational research. This review summarizes the most important findings in this active research area, covering the preconditioning triggers, potential mechanisms, mediators, and functional benefits for stem cell transplant therapy.

Keywords

Stem cell preconditioning Stroke Ischemia Neurodegenerative disorder Heart attack 

Abbreviations

BDNF

Brain-derived neurotrophic factor

CoPP

Cobalt protoporphyrin

Cx43

Connexin-43

CXCR

CXC chemokine receptor

EPO

Erythropoietin

ERK

Extracellular signal-regulated kinase

FAK

Focal adhesion kinase

GSK-3β

Glycogen synthase kinase-3β

HIF-1

Hypoxia-inducible factor-1

HSPs

Heat shock protein

IGF-1

Insulin-like growth factor-1

IL-1β

Interleukin-1beta

IL-6

Interleukin-6

LPS

Lipopolysaccharide

miR

micro-RNA

MMP

Matrix metalloproteinase

NOS

Nitric oxide synthase

polyP

Polyphosphate

PTP

Permeability transition pore

ROS

Reactive oxygen species

SDF-1

Stromal-derived factor-1

TNF-α

Tumor necrosis factor alpha

VEGF

Vascular endothelial growth factor

Notes

Acknowledgments

This work was supported by NIH grants NS062097, NS058710, NS057255, and AHA Established Investigator Award 0840110N. Zheng Wei was a visiting Ph.D. student from Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.

Conflict of Interest Statement

All authors declare that they have no conflict of interest.

References

  1. 1.
    Deveau T, Yu SP, Wei L. Cellular therapy for ischemic stroke. In: Lapchak PA, Zhang JH, editors. Translational stroke research: from target selection to clinical trials. New York: Springer; 2012. p. 777–814.CrossRefGoogle Scholar
  2. 2.
    Doorn J, Moll G, Le Blanc K, van Blitterswijk C, de Boer J. Therapeutic applications of mesenchymal stromal cells: paracrine effects and potential improvements. Tissue Eng Part B Rev. 2012;18:101–15.PubMedCrossRefGoogle Scholar
  3. 3.
    Haider KH, Ashraf M. Preconditioning approach in stem cell therapy for the treatment of infarcted heart. Prog Mol Biol Transl Sci. 2012;111:323–56.PubMedCrossRefGoogle Scholar
  4. 4.
    Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: underlying mechanisms and clinical application. Atherosclerosis. 2009;204:334–41.PubMedCrossRefGoogle Scholar
  5. 5.
    Perez-Pinzon MA. Mechanisms of neuroprotection during ischemic preconditioning: lessons from anoxic tolerance. Comp Biochem Physiol Mol Integr Physiol. 2007;147:291–9.CrossRefGoogle Scholar
  6. 6.
    Grimm C, Wenzel A, Groszer M, Mayser H, Seeliger M, Samardzija M, et al. HIF-1-induced erythropoietin in the hypoxic retina protects against light-induced retinal degeneration. Nat Med. 2002;8:718–24.PubMedCrossRefGoogle Scholar
  7. 7.
    Trendelenburg G, Dirnagl U. Neuroprotective role of astrocytes in cerebral ischemia: focus on ischemic preconditioning. Glia. 2005;50:307–20.PubMedCrossRefGoogle Scholar
  8. 8.
    Ran R, Xu H, Lu A, Bernaudin M, Sharp FR. Hypoxia preconditioning in the brain. Dev Neurosci. 2005;27:87–92.PubMedCrossRefGoogle Scholar
  9. 9.
    Li, Y, Yu, SP, Mohamad, O, Genetta, T, Wei, L, Sublethal Transient Global Ischemia Stimulates Migration of Neuroblasts and Neurogenesis in Mice. In: Translational stroke research. New York: Springer; 2010. p. 184–196Google Scholar
  10. 10.
    Przyklenk K, Whittaker P. Remote ischemic preconditioning: current knowledge, unresolved questions, and future priorities. J Cardiovasc Pharmacol Ther. 2011;16:255–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Fairbanks SL, Brambrink AM. Preconditioning and postconditioning for neuroprotection: the most recent evidence. Best Pract Res Clin Anaesthesiol. 2010;24:521–34.PubMedCrossRefGoogle Scholar
  12. 12.
    Koch S, Katsnelson M, Dong CH, Perez-Pinzon M. Remote ischemic limb preconditioning after subarachnoid hemorrhage a phase Ib study of safety and feasibility. Stroke. 2011;42:1387–91.PubMedCrossRefGoogle Scholar
  13. 13.
    Dirnagl U, Becker K, Meisel A. Preconditioning and tolerance against cerebral ischaemia: from experimental strategies to clinical use. Lancet Neurol. 2009;8:398–412.PubMedCrossRefGoogle Scholar
  14. 14.
    Hu XY, Yu SP, Fraser JL, Lu ZY, Ogle ME, Wang JA, et al. Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. J Thorac Cardiovasc Surg. 2008;135:799–808.PubMedCrossRefGoogle Scholar
  15. 15.
    Wei L, Fraser JL, Lu ZY, Hu XY, Yu SP. Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and neurogenesis after cerebral ischemia in rats. Neurobiol Dis. 2012;46:635–45.PubMedCrossRefGoogle Scholar
  16. 16.
    Theus MH, Wei L, Cui L, Francis K, Hu XY, Keogh C, et al. In vitro hypoxic preconditioning of embryonic stem cells as a strategy of promoting cell survival and functional benefits after transplantation into the ischemic rat brain. Exp Neurol. 2008;210:656–70.PubMedCrossRefGoogle Scholar
  17. 17.
    Ogle ME, Yu SP, Wei L. Primed for lethal battle: a step forward to enhance the efficacy and efficiency of stem cell transplantation therapy. J Thorac Cardiovasc Surg. 2009;138:527–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Ii M, Nishimura H, Iwakura A, Wecker A, Eaton E, Asahara T, et al. Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via “imported” nitric oxide synthase activity. Circulation. 2005;111:1114–20.PubMedCrossRefGoogle Scholar
  19. 19.
    Yan FD, Yao YY, Chen LJ, Li YF, Sheng ZL, Ma GS. Hypoxic preconditioning improves survival of cardiac progenitor cells: role of stromal cell derived factor-1 alpha-CXCR4 axis. PLoS One. 2012;7:9.CrossRefGoogle Scholar
  20. 20.
    Stubbs SL, Hsiao STF, Peshavariya HM, Lim SY, Dusting GJ, Dilley RJ. Hypoxic preconditioning enhances survival of human adipose-derived stem cells and conditions endothelial cells in vitro. Stem Cells Dev. 2012;21:1887–96.PubMedCrossRefGoogle Scholar
  21. 21.
    Aly A, Peterson KM, Lerman A, Lerman LO, Rodriguez-Porcel M. Role of oxidative stress in hypoxia preconditioning of cells transplanted to the myocardium: a molecular imaging study. J Cardiovasc Surg. 2011;52:579–85.Google Scholar
  22. 22.
    Peterson KM, Aly A, Lerman A, Lerman LO, Rodriguez-Porcel M. Improved survival of mesenchymal stromal cell after hypoxia preconditioning: role of oxidative stress. Life Sci. 2011;88:65–73.PubMedCrossRefGoogle Scholar
  23. 23.
    Das R, Jahr H, van Osch G, Farrell E. The role of hypoxia in bone marrow-derived mesenchymal stem cells: considerations for regenerative medicine approaches. Tissue Eng Part B Rev. 2010;16:159–68.PubMedCrossRefGoogle Scholar
  24. 24.
    Wang JA, He A, Hu XY, Jiang Y, Sun Y, Jiang J, et al. Anoxic preconditioning: a way to enhance the cardioprotection of mesenchymal stem cells. Int J Cardiol. 2009;133:410–2.PubMedCrossRefGoogle Scholar
  25. 25.
    Li JH, Zhang N, Wang JA. Improved anti-apoptotic and anti-remodeling potency of bone marrow mesenchyma stem cells by anoxic pre-conditioning in diabetic cardiomyopathy. J Endocrinol Investig. 2008;31:103–10.Google Scholar
  26. 26.
    He AN, Jiang Y, Gui C, Sun Y, Li JH, Wang JA. The antiapoptotic effect of mesenchymal stem cell transplantation on ischemic myocardium is enhanced by anoxic preconditioning. Can J Cardiol. 2009;25:353–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Xie XX, Sun AJ, Zhu WQ, Huang ZY, Hu XY, Jia JG, et al. Transplantation of mesenchymal stem cells preconditioned with hydrogen sulfide enhances repair of myocardial infarction in rats. Tohoku J Exp Med. 2012;226:29–36.PubMedCrossRefGoogle Scholar
  28. 28.
    Zhang J, Chen G-H, Wang Y-W, Zhao J, Duan H-F, Liao L-M, et al. Hydrogen peroxide preconditioning enhances the therapeutic efficacy of Wharton’s jelly mesenchymal stem cells after myocardial infarction. Chin Med J. 2012;125:3472–8.PubMedGoogle Scholar
  29. 29.
    Kondo-Nakamura M, Shintani-Ishida K, Uemura K, Yoshida K. Brief exposure to carbon monoxide preconditions cardiomyogenic cells against apoptosis in ischemia-reperfusion. Biochem Biophys Res Commun. 2010;393:449–54.PubMedCrossRefGoogle Scholar
  30. 30.
    Li Y, Lu ZY, Keogh CL, Yu SP, Wei L. Erythropoietin-induced neurovascular protection, angiogenesis, and cerebral blood flow restoration after focal ischemia in mice. J Cereb Blood Flow Metab. 2007;27:1043–54.PubMedGoogle Scholar
  31. 31.
    Pasha Z, Wang Y, Sheikh R, Zhang D, Zhao T, Ashraf M. Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium. Cardiovasc Res. 2008;77:134–42.PubMedCrossRefGoogle Scholar
  32. 32.
    Zemani F, Silvestre JS, Fauvel-Lafeve F, Bruel A, Vilar J, Bieche I, et al. Ex vivo priming of endothelial progenitor cells with SDF-1 before transplantation could increase their proangiogenic potential. Arterioscler Thromb Vasc Biol. 2008;28:644–50.PubMedCrossRefGoogle Scholar
  33. 33.
    Chen J, Du XL, Zhang KL. Effects of stromal-derived factor 1 preconditioning on apoptosis of rat bone mesenchymal stem cells. J Huazhong Univ Sci Tech-Med Sci. 2009;29:423–6.CrossRefGoogle Scholar
  34. 34.
    Lu G, Ashraf M, Haider KH. Insulin-like growth factor-1 preconditioning accentuates intrinsic survival mechanism in stem cells to resist ischemic injury by orchestrating protein kinase C alpha-Erk1/2 activation. Antioxid Redox Signal. 2012;16:217–27.PubMedCrossRefGoogle Scholar
  35. 35.
    Tilkorn DJ, Davies EM, Keramidaris E, Dingle AM, Gerrand YW, Taylor CJ, et al. The in vitro preconditioning of myoblasts to enhance subsequent survival in an in vivo tissue engineering chamber model. Biomaterials. 2012;33:3868–79.PubMedCrossRefGoogle Scholar
  36. 36.
    Jiang BM, Xiao WM, Shi YZ, Liu MD, Xiao XZ. Heat shock pretreatment inhibited the release of Smac/DIABLO from mitochondria and apoptosis induced by hydrogen peroxide in cardiomyocytes and C2C12 myogenic cells. Cell Stress Chaperones. 2005;10:252–62.PubMedCrossRefGoogle Scholar
  37. 37.
    Cui XJ, Wang HJ, Guo HD, Wang C, Ao H, Liu XQ, et al. Transplantation of mesenchymal stem cells preconditioned with diazoxide, a mitochondrial ATP-sensitive potassium channel opener promotes repair of myocardial infarction in rats. Tohoku J Exp Med. 2010;220:139–47.PubMedCrossRefGoogle Scholar
  38. 38.
    Niagara MI, Haider HK, Jiang SJ, Ashraf M. Pharmacologically preconditioned skeletal myoblasts are resistant to oxidative stress and promote angiomyogenesis via release of paracrine factors in the infarcted heart. Circ Res. 2007;100:545–55.PubMedCrossRefGoogle Scholar
  39. 39.
    Idris NM, Ashraf M, Ahmed RPH, Jiang SJ, Haider KH. Activation of IL-11/STAT3 pathway in preconditioned human skeletal myoblasts blocks apoptotic cascade under oxidant stress. Regen Med. 2012;7:47–57.PubMedCrossRefGoogle Scholar
  40. 40.
    Afzal MR, Haider HK, Idris NM, Jiang SJ, Ahmed RPH, Ashraf M. Preconditioning promotes survival and angiomyogenic potential of mesenchymal stem cells in the infarcted heart via NF-kappa B signaling. Antioxid Redox Signal. 2010;12:693–702.PubMedCrossRefGoogle Scholar
  41. 41.
    Li LF, Zeng H, Chen JX. Apelin-13 increases myocardial progenitor cells and improves repair postmyocardial infarction. Am J Physiol Heart Circ Physiol. 2012;303:605–18.CrossRefGoogle Scholar
  42. 42.
    Kim JH, Oh AY, Choi YM, Ku SY, Kim YY, Lee NJ, et al. Isoflurane decreases death of human embryonic stem cell-derived, transcriptional marker Nkx2.5(+) cardiac progenitor cells. Acta Anaesthesiol Scand. 2011;55:1124–31.PubMedCrossRefGoogle Scholar
  43. 43.
    Yao YW, Zhang FM, Wang LS, Zhang GH, Wang ZJ, Chen JM, et al. Lipopolysaccharide preconditioning enhances the efficacy of mesenchymal stem cells transplantation in a rat model of acute myocardial infarction. J Biomed Sci. 2009;16:11.CrossRefGoogle Scholar
  44. 44.
    Cai C, Teng L, Vu D, He J-Q, Guo Y, Li Q, et al. The heme oxygenase 1 inducer (CoPP) protects human cardiac stem cells against apoptosis through activation of the extracellular signal-regulated kinase (ERK)/NRF2 signaling pathway and cytokine release. J Biol Chem. 2012;287:33720–32.PubMedCrossRefGoogle Scholar
  45. 45.
    Haider HK, Ashraf M. Strategies to promote donor cell survival: combining preconditioning approach with stem cell transplantation. J Mol Cell Cardiol. 2008;45:554–66.PubMedCrossRefGoogle Scholar
  46. 46.
    Haider HK, Ashraf M. Preconditioning and stem cell survival. J Cardiovasc Transl Res. 2010;3:89–102.PubMedCrossRefGoogle Scholar
  47. 47.
    Liu HB, Xue WJ, Ge GQ, Luo XH, Li Y, Xiang HL, et al. Hypoxic preconditioning advances CXCR4 and CXCR7 expression by activating HIF-1 alpha in MSCs. Biochem Biophys Res Commun. 2010;401:509–15.PubMedCrossRefGoogle Scholar
  48. 48.
    Zeng XJ, Yu SP, Taylor T, Ogle M, Wei L. Protective effect of apelin on cultured rat bone marrow mesenchymal stem cells against apoptosis. Stem Cell Res. 2012;8:357–67.PubMedCrossRefGoogle Scholar
  49. 49.
    Wisel S, Khan M, Kuppusamy ML, Mohan IK, Chacko SM, Rivera BK, et al. Pharmacological preconditioning of mesenchymal stem cells with trimetazidine (1–2,3,4-trimethoxybenzyl piperazine) protects hypoxic cells against oxidative stress and enhances recovery of myocardial function in infarcted heart through Bcl-2 expression. J Pharmacol Exp Ther. 2009;329:543–50.PubMedCrossRefGoogle Scholar
  50. 50.
    Choi KE, Hall CL, Sun JM, Wei L, Mohamad O, Dix TA, et al. A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice. FASEB J. 2012;26:2799–810.PubMedCrossRefGoogle Scholar
  51. 51.
    Ogle ME, Gu XH, Espinera AR, Wei L. Inhibition of prolyl hydroxylases by dimethyloxaloylglycine after stroke reduces ischemic brain injury and requires hypoxia inducible factor-1 alpha. Neurobiol Dis. 2012;45:733–42.PubMedCrossRefGoogle Scholar
  52. 52.
    Semenza GL. Hypoxia-inducible factor 1: regulator of mitochondrial metabolism and mediator of ischemic preconditioning. Biochim Biophys Acta-Mol Cell Res. 2011;1813:1263–8.CrossRefGoogle Scholar
  53. 53.
    Dehne N, Brune B. HIF-1 in the inflammatory microenvironment. Exp Cell Res. 2009;315:1791–7.PubMedCrossRefGoogle Scholar
  54. 54.
    Greer SN, Metcalf JL, Wang Y, Ohh M. The updated biology of hypoxia-inducible factor. EMBO J. 2012;31:2448–60.PubMedCrossRefGoogle Scholar
  55. 55.
    Valsecchi V, Pignataro G, Del Prete A, Sirabella R, Matrone C, Boscia F, et al. NCX1 is a novel target gene for hypoxia-inducible factor-1 in ischemic brain preconditioning. Stroke. 2011;42:754–63.PubMedCrossRefGoogle Scholar
  56. 56.
    Keogh CL, Yu SP, Wei L. The effect of recombinant human erythropoietin on neurovasculature repair after focal ischemic stroke in neonatal rats. J Pharmacol Exp Ther. 2007;322:521–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Li WL, Fraser JL, Yu SP, Zhu J, Jiang YJ, Wei L. The role of VEGF/VEGFR2 signaling in peripheral stimulation-induced cerebral neurovascular regeneration after ischemic stroke in mice. Exp Brain Res. 2011;214:503–13.PubMedCrossRefGoogle Scholar
  58. 58.
    Li WL, Yu SP, Ogle ME, Ding XS, Wei L. Enhanced neurogenesis and cell migration following focal ischemia and peripheral stimulation in mice. Dev Neurobiol. 2008;68:1474–86.PubMedCrossRefGoogle Scholar
  59. 59.
    Whitaker VR, Cui L, Miller S, Yu SP, Wei L. Whisker stimulation enhances angiogenesis in the barrel cortex following focal ischemia in mice. J Cereb Blood Flow Metab. 2007;27:57–68.PubMedCrossRefGoogle Scholar
  60. 60.
    Peng H, Wu Y, Duan Z, Ciborowski P, Zheng JC. Proteolytic processing of SDF-1alpha by matrix metalloproteinase-2 impairs CXCR4 signaling and reduces neural progenitor cell migration. Protein Cell. 2012;3:875–82.PubMedCrossRefGoogle Scholar
  61. 61.
    Mahfoudh-Boussaid A, Zaouali MA, Hadj-Ayed K, Miled AH, Saidane-Mosbahi D, Rosello-Catafau J, et al. Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1 alpha in ischemic kidney: the role of nitric oxide. J Biomed Sci. 2011;19:8.Google Scholar
  62. 62.
    Robinson MA, Baumgardner JE, Otto CM. Oxygen-dependent regulation of nitric oxide production by inducible nitric oxide synthase. Free Radic Biol Med. 2011;51:1952–65.PubMedCrossRefGoogle Scholar
  63. 63.
    Liu XB, Wang JA, Ogle ME, Wei L. Prolyl hydroxylase inhibitor dimethyloxalylglycine enhances mesenchymal stem cell survival. J Cell Biochem. 2009;106:903–11.PubMedCrossRefGoogle Scholar
  64. 64.
    Sims B, Clarke M, Francillion L, Kindred E, Hopkins ES, Sontheimer H. Hypoxic preconditioning involves system Xc(−) regulation in mouse neural stem cells. Stem Cell Res. 2012;8:285–91.PubMedCrossRefGoogle Scholar
  65. 65.
    Shih AY, Erb H, Sun X, Toda S, Kalivas PW, Murphy TH. Cystine/glutamate exchange modulates glutathione supply for neuroprotection from oxidative stress and cell proliferation. J Neurosci. 2006;26:10514–23.PubMedCrossRefGoogle Scholar
  66. 66.
    Cerrada, I, Ruiz-Sauri, A, Carrero, R, Trigueros, C, Dorronsoro, A, Sanchez-Puelles, JM, Diez-Juan, A, Montero, JA, Sepulveda, P. Hypoxia-inducible factor 1 alpha contributes to cardiac healing in mesenchymal stem cells-mediated cardiac repair. Stem Cells Dev. 2012; (in press)Google Scholar
  67. 67.
    Park J, Park H-H, Choi H, Seo Kim Y, Yu H-J, Lee K-Y, et al. Coenzyme Q10 protects neural stem cells against hypoxia by enhancing survival signals. Brain Res. 2012;1478:64–73.PubMedCrossRefGoogle Scholar
  68. 68.
    Dirnagl U, Meisel A. Endogenous neuroprotection: mitochondria as gateways to cerebral preconditioning. Neuropharmacology. 2008;55:334–44.PubMedCrossRefGoogle Scholar
  69. 69.
    Ravati A, Ahlemeyer B, Becker A, Klumpp S, Krieglstein J. Preconditioning-induced neuroprotection is mediated by reactive oxygen species and activation of the transcription factor nuclear factor-kappa B. J Neurochem. 2001;78:909–19.PubMedCrossRefGoogle Scholar
  70. 70.
    Jou MJ. Pathophysiological and pharmacological implications of mitochondria-targeted reactive oxygen species generation in astrocytes. Adv Drug Deliv Rev. 2008;60:1512–26.PubMedCrossRefGoogle Scholar
  71. 71.
    Tang XQ, Feng JQ, Chen J, Chen PX, Zhi JL, Cui Y, et al. Protection of oxidative preconditioning against apoptosis induced by H2O2 in PC12 cells: mechanisms via MMP, ROS, and Bcl-2. Brain Res. 2005;1057:57–64.PubMedCrossRefGoogle Scholar
  72. 72.
    Xiao L, Lan A, Mo L, Xu W, Jiang N, Hu F, et al. Hydrogen sulfide protects PC12 cells against reactive oxygen species and extracellular signal-regulated kinase 1/2-mediated downregulation of glutamate transporter-1 expression induced by chemical hypoxia. Int J Mol Med. 2012;30:1126–32.PubMedGoogle Scholar
  73. 73.
    Waszak P, Alphonse R, Vadivel A, Ionescu L, Eaton F, Thebaud B. Preconditioning enhances the paracrine effect of mesenchymal stem cells in preventing oxygen-induced neonatal lung injury in rats. Stem Cells Dev. 2012;21:2789–97.PubMedCrossRefGoogle Scholar
  74. 74.
    Furuichi T, Liu WL, Shi HL, Miyake M, Liu KJ. Generation of hydrogen peroxide during brief oxygen-glucose deprivation induces preconditioning neuronal protection in primary cultured neurons. J Neurosci Res. 2005;79:816–24.PubMedCrossRefGoogle Scholar
  75. 75.
    Sakata H, Niizuma K, Yoshioka H, Kim GS, Jung JE, Katsu M, et al. Minocycline-preconditioned neural stem cells enhance neuroprotection after ischemic stroke in rats. J Neurosci. 2012;32:3462–73.PubMedCrossRefGoogle Scholar
  76. 76.
    Seidlmayer LK, Gomez-Garcia MR, Blatter LA, Pavlov E, Dedkova EN. Inorganic polyphosphate is a potent activator of the mitochondrial permeability transition pore in cardiac myocytes. J Gen Physiol. 2012;139:321–31.PubMedCrossRefGoogle Scholar
  77. 77.
    Abramov AY, Fraley C, Diao CT, Winkfein R, Colicos MA, Duchen MR, et al. Targeted polyphosphatase expression alters mitochondrial metabolism and inhibits calcium-dependent cell death. Proc Natl Acad Sci U S A. 2007;104:18091–6.PubMedCrossRefGoogle Scholar
  78. 78.
    Wang JA, Chen TL, Jiang J, Shi H, Gui C, Luo RH, et al. Hypoxic preconditioning attenuates hypoxia/reoxygenation-induced apoptosis in mesenchymal stem cells. Acta Pharmacol Sin. 2008;29:74–82.PubMedCrossRefGoogle Scholar
  79. 79.
    Sepac A, Sedlic F, Si-Tayeb K, Lough J, Duncan SA, Bienengraeber M, et al. Isoflurane preconditioning elicits competent endogenous mechanisms of protection from oxidative stress in cardiomyocytes derived from human embryonic stem cells. Anesthesiology. 2010;113:906–16.PubMedCrossRefGoogle Scholar
  80. 80.
    Fretwell L, Dickenson JM. Role of large-conductance Ca2+ −activated potassium channels in adenosine A(1) receptor-mediated pharmacological preconditioning in H9c2 cells. Eur J Pharmacol. 2009;618:37–44.PubMedCrossRefGoogle Scholar
  81. 81.
    Simerabet M, Robin E, Aristi I, Adamczyk S, Tavernier B, Vallet B, et al. Preconditioning by an in situ administration of hydrogen peroxide: involvement of reactive oxygen species and mitochondrial ATP-dependent potassium channel in a cerebral ischemia-reperfusion model. Brain Res. 2008;1240:177–84.PubMedCrossRefGoogle Scholar
  82. 82.
    Sheng R, Liu XQ, Zhang LS, Gao B, Han R, Wu YQ, et al. Autophagy regulates endoplasmic reticulum stress in ischemic preconditioning. Autophagy. 2012;8:310–25.PubMedCrossRefGoogle Scholar
  83. 83.
    Park HK, Chu K, Jung KH, Lee ST, Bahn JJ, Kim M, et al. Autophagy is involved in the ischemic preconditioning. Neurosci Lett. 2009;451:16–9.PubMedCrossRefGoogle Scholar
  84. 84.
    Yeh CH, Hsu SP, Yang CC, Chien CT, Wang NP. Hypoxic preconditioning reinforces HIF-alpha-dependent HSP70 signaling to reduce ischemic renal failure-induced renal tubular apoptosis and autophagy. Life Sci. 2010;86:115–23.PubMedCrossRefGoogle Scholar
  85. 85.
    Rodriguez-Sinovas A, Boengler K, Cabestrero A, Gres P, Morente M, Ruiz-Meana M, et al. Translocation of connexin 43 to the inner mitochondrial membrane of cardiomyocytes through the heat shock protein 90-dependent TOM pathway and its importance for cardioprotection. Circ Res. 2006;99:93–101.PubMedCrossRefGoogle Scholar
  86. 86.
    Fontes MSC, van Veen LAB, de Bakker JMT, van Rijen HVM. Functional consequences of abnormal Cx43 expression in the heart. Biochim Biophys Acta-Biomembr. 2012;1818:2020–9.CrossRefGoogle Scholar
  87. 87.
    Axelsen LN, Stahlhut M, Mohammed S, Larsen BD, Nielsen MS, Holstein-Rathlou NH, et al. Identification of ischemia-regulated phosphorylation sites in connexin43: a possible target for the antiarrhythmic peptide analogue rotigaptide (ZP123). J Mol Cell Cardiol. 2006;40:790–8.PubMedCrossRefGoogle Scholar
  88. 88.
    Lu G, Haider HK, Jiang SJ, Ashraf M. Sca-1(+) stem cell survival and engraftment in the infarcted heart dual role for preconditioning-induced connexin-43. Circulation. 2009;119:2587–96.PubMedCrossRefGoogle Scholar
  89. 89.
    Orellana JA, Froger N, Ezan P, Jiang JX, Bennett MVL, Naus CC, et al. ATP and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels. J Neurochem. 2011;118:826–40.PubMedCrossRefGoogle Scholar
  90. 90.
    Lin JHC, Lou N, Kang N, Takano T, Hu F, Han XN, et al. A central role of connexin 43 in hypoxic preconditioning. J Neurosci. 2008;28:681–95.PubMedCrossRefGoogle Scholar
  91. 91.
    Jaderstad J, Brismar H, Herlenius E. Hypoxic preconditioning increases gap-junctional graft and host communication. Neuroreport. 2010;21:1126–32.PubMedCrossRefGoogle Scholar
  92. 92.
    Lu G, Jiang SJ, Ashraf M, Haider KH. Subcellular preconditioning of stem cells: mito-Cx43 gene targeting is cytoprotective via shift of mitochondrial Bak and Bcl-xL balance. Regen Med. 2012;7:323–34.PubMedCrossRefGoogle Scholar
  93. 93.
    Lu G, Haider HK, Porollo A, Ashraf M. Mitochondria-specific transgenic overexpression of connexin-43 simulates preconditioning-induced cytoprotection of stem cells. Cardiovasc Res. 2010;88:277–86.PubMedCrossRefGoogle Scholar
  94. 94.
    Wang DG, Shen WZ, Zhang FX, Chen ML, Chen HW, Cao KJ. Connexin43 promotes survival of mesenchymal stem cells in ischaemic heart. Cell Biol Int. 2010;34:415–23.PubMedCrossRefGoogle Scholar
  95. 95.
    Ahmad Waza A, Andrabi K, Ul Hussain M. Adenosine-triphosphate-sensitive K(+)channel (Kir6.1): a novel phosphospecific interaction partner of connexin 43 (Cx43). Exp Cell Res. 2012;318:2559–66.PubMedCrossRefGoogle Scholar
  96. 96.
    Rottlaender D, Boengler K, Wolny M, Michels G, Endres-Becker J, Motloch LJ, et al. Connexin 43 acts as a cytoprotective mediator of signal transduction by stimulating mitochondrial K-ATP channels in mouse cardiomyocytes. J Clin Investig. 2010;120:1441–53.PubMedCrossRefGoogle Scholar
  97. 97.
    Du WJ, Li JK, Wang QY, Hou JB, Yu B. Lithium chloride preconditioning optimizes skeletal myoblast functions for cellular cardiomyoplasty in vitro via glycogen synthase kinase-3 beta/beta-catenin signaling. Cells Tissues Organs. 2009;190:11–9.PubMedCrossRefGoogle Scholar
  98. 98.
    Sierra MD, Yang FQ, Narazaki M, Salvucci O, Davis D, Yarchoan R, et al. Differential processing of strornal-derived factor-1 alpha and stromal-derived factor-1 beta explains functional diversity. Blood. 2004;103:2452–9.CrossRefGoogle Scholar
  99. 99.
    Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol. 2002;3:687–94.PubMedCrossRefGoogle Scholar
  100. 100.
    Sharma M, Afrin F, Satija N, Tripathi RP, Gangenahalli GU. Stromal-derived factor-1/CXCR4 signaling: indispensable role in homing and engraftment of hematopoietic stem cells in bone marrow. Stem Cells Dev. 2011;20:933–46.PubMedCrossRefGoogle Scholar
  101. 101.
    Zhao DH, Najbauer J, Garcia E, Metz MZ, Gutova M, Glackin CA, et al. Neural stem cell tropism to glioma: critical role of tumor hypoxia. Mol Cancer Res. 2008;6:1819–29.PubMedCrossRefGoogle Scholar
  102. 102.
    Hung SC, Pochampally RR, Hsu SC, Sanchez C, Chen SC, Spees J, et al. Short-term exposure of multipotent stromal cells to low oxygen increases their expression of cx3cr1 and cxcr4 and their engraftment in vivo. PLoS One. 2007;2:11.CrossRefGoogle Scholar
  103. 103.
    Kubo M, Li TS, Kamota T, Ohshima M, Qin SL, Hamano K. Increased expression of CXCR4 and integrin alpha m in hypoxia-preconditioned cells contributes to improved cell retention and angiogenic potency. J Cell Physiol. 2009;220:508–14.PubMedCrossRefGoogle Scholar
  104. 104.
    Tang YL, Zhu WQ, Cheng M, Chen LJ, Zhang J, Sun T, et al. Hypoxic preconditioning enhances the benefit of cardiac progenitor cell therapy for treatment of myocardial infarction by inducing CXCR4 expression. Circ Res. 2009;104:1209–U218.PubMedCrossRefGoogle Scholar
  105. 105.
    Cencioni C, Capogrossi MC, Napolitano M. The SDF-1/CXCR4 axis in stem cell preconditioning. Cardiovasc Res. 2012;94:400–7.PubMedCrossRefGoogle Scholar
  106. 106.
    Ong LL, Li WZ, Oldigs JK, Kaminski A, Gerstmayer B, Piechaczek C, et al. Hypoxic/normoxic preconditioning increases endothelial differentiation potential of human bone marrow cd133+ cells. Tissue Eng Part C Methods. 2010;16:1069–81.PubMedCrossRefGoogle Scholar
  107. 107.
    Lin JS, Chen YS, Chiang HS, Ma MC. Hypoxic preconditioning protects rat hearts against ischaemia-reperfusion injury: role of erythropoietin on progenitor cell mobilization. J Physiol-Lond. 2008;586:5757–69.PubMedCrossRefGoogle Scholar
  108. 108.
    Miller JT, Bartley JH, Wimborne HJC, Walker AL, Hess DC, Hill WD, et al. The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12) expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic–ischemic injury. BMC Neurosci. 2005;6:11.CrossRefGoogle Scholar
  109. 109.
    Gao H, Priebe W, Glod J, Banerjee D. Activation of signal transducers and activators of transcription 3 and focal adhesion kinase by stromal cell-derived factor 1 is required for migration of human mesenchymal stem cells in response to tumor cell-conditioned medium. Stem Cells. 2009;27:857–65.PubMedCrossRefGoogle Scholar
  110. 110.
    Zheng H, Fu GS, Dai T, Huang H. Migration of endothelial progenitor cells mediated by stromal cell-derived factor-1 alpha/CXCR4 via PI3K/Akt/eNOS signal transduction pathway. J Cardiovasc Pharmacol. 2007;50:274–80.PubMedCrossRefGoogle Scholar
  111. 111.
    Kim HW, Mallick F, Durrani S, Ashraf M, Jiang SJ, Haider KH. Concomitant activation of mir-107/pdcd10 and hypoxamir-210/casp8ap2 and their role in cytoprotection during ischemic preconditioning of stem cells. Antioxid Redox Signal. 2012;17:1053–65.PubMedCrossRefGoogle Scholar
  112. 112.
    Meng S, Cao JT, Wang LS, Zhou Q, Li YG, Shen CX, et al. Microrna 107 partly inhibits endothelial progenitor cells differentiation via hif-1 beta. PLoS One. 2012;7:7.Google Scholar
  113. 113.
    Suzuki Y, Kim HW, Ashraf M, Haider HK. Diazoxide potentiates mesenchymal stem cell survival via NF-kappa B-dependent miR-146a expression by targeting fas. Am J Physiol Heart Circ Physiol. 2010;299:H1077–82.PubMedCrossRefGoogle Scholar
  114. 114.
    Kostjuk S, Loseva P, Chvartatskaya O, Ershova E, Smirnova T, Malinovskaya E, et al. Extracellular GC-rich DNA activates TLR9-and NF-kB-dependent signaling pathways in human adipose-derived mesenchymal stem cells (haMSCs). Expert Opin Biol Ther. 2012;12:S99–111.PubMedCrossRefGoogle Scholar
  115. 115.
    Francis KR, Wei L. Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning. Cell Death Dis. 2010;1:11.CrossRefGoogle Scholar
  116. 116.
    Lin C, Jun J, Ling W, Xin Z, Fraser JL, Snider BJ, et al. Transplantation of embryonic stem cells improves nerve repair and functional recovery after severe sciatic nerve axotomy in rats. Stem Cells. 2008;26:1356–65.CrossRefGoogle Scholar
  117. 117.
    Khan M, Akhtar S, Mohsin S, Khan SN, Riazuddin S. Growth factor preconditioning increases the function of diabetes-impaired mesenchymal stem cells. Stem Cells Dev. 2011;20:67–75.PubMedCrossRefGoogle Scholar
  118. 118.
    Hoke NN, Salloum FN, Kass DA, Das A, Kukreja RC. Preconditioning by phosphodiesterase-5 inhibition improves therapeutic efficacy of adipose-derived stem cells following myocardial infarction in mice. Stem Cells. 2012;30:326–35.PubMedCrossRefGoogle Scholar
  119. 119.
    Herrmann JL, Wang Y, Abarbanell AM, Weil BR, Tan JN, Meldrum DR. Preconditiong mesenchymal stem cells with transforming growth factor-α improves mesenchymal stem cell-mediated cardioprotection. Shock. 2010;33:24–30.PubMedCrossRefGoogle Scholar
  120. 120.
    Efimenko A, Starostina E, Kalinina N, Stolzing A. Angiogenic properties of aged adipose derived mesenchymal stem cells after hypoxic conditioning. J Transl Med. 2011;9:13.CrossRefGoogle Scholar
  121. 121.
    Chang C-P, Chio C-C, Cheong C-U, Chao C-M, Cheng B-C, Lin M-T. Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury. Clin Sci (Lond). 2013;124:165–76.CrossRefGoogle Scholar
  122. 122.
    Mohamad O, Chen DD, Zhang LL, Hofmann C, Wei L, Yu SP. Erythropoietin reduces neuronal cell death and hyperalgesia induced by peripheral inflammatory pain in neonatal rats. Mol Pain. 2011;7:15.CrossRefGoogle Scholar
  123. 123.
    Li JM, Li JP, Zhang X, Lu ZY, Yu SP, Wei L. Expression of heparanase in vascular cells and astrocytes of the mouse brain after focal cerebral ischemia. Brain Res. 2012;1433:137–44.PubMedCrossRefGoogle Scholar
  124. 124.
    Hu X, Wei L, Taylor TM, Wei J, Zhou X, Wang J-A, et al. Hypoxic preconditioning enhances bone marrow mesenchymal stem cell migration via Kv2.1 channel and FAK activation. Am J Physiol Cell Physiol. 2011;301:C362–72.PubMedCrossRefGoogle Scholar
  125. 125.
    Kamota T, Li TS, Morikage N, Murakami M, Ohshima M, Kubo M, et al. Ischemic pre-conditioning enhances the mobilization and recruitment of bone marrow stem cells to protect against ischemia/reperfusion injury in the late phase. J Am Coll Cardiol. 2009;53:1814–22.PubMedCrossRefGoogle Scholar
  126. 126.
    Li SY, Deng YB, Feng JQ, Ye WB. Oxidative preconditioning promotes bone marrow mesenchymal stem cells migration and prevents apoptosis. Cell Biol Int. 2009;33:411–8.PubMedCrossRefGoogle Scholar
  127. 127.
    Rosova 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;26:2173–82.PubMedCrossRefGoogle Scholar
  128. 128.
    Hayakawa J, Migita M, Ueda T, Fukazawa R, Adachi K, Ooue Y, et al. Dextran sulfate and stromal cell derived factor-1 promote cxcr4 expression and improve bone marrow homing efficiency of infused hematopoietic stem cells. J Nippon Med School. 2009;76:198–208.CrossRefGoogle Scholar
  129. 129.
    Wei J-F, Wei L, Zhou X, Lu Z-Y, Francis K, Hu X-Y, et al. Formation of Kv2.1-FAK complex as a mechanism of FAK activation, cell polarization and enhanced motility. J Cell Physiol. 2008;217:544–57.PubMedCrossRefGoogle Scholar
  130. 130.
    Wei, J-F, Wei, L, Zhou, X, Lu, Z-Y, Francis, K, Hu, X-Y, Liu, Y, Xiong, W-C, Zhang, X, Banik, NL, Zheng, S-S, Yu, SP. Formation of Kv2.1-FAK complex as a mechanism of FAK activation, cell polarization and enhanced motility. J Cell Physiol. 2008;217(2):544–57.Google Scholar
  131. 131.
    Rota C, Imberti B, Pozzobon M, Piccoli M, De Coppi P, Atala A, et al. Human amniotic fluid stem cell preconditioning improves their regenerative potential. Stem Cells Dev. 2012;21:1911–23.PubMedCrossRefGoogle Scholar
  132. 132.
    Gyongyosi M, Posa A, Pavo N, Hemetsberger R, Kvakan H, Steiner-Boker S, et al. Differential effect of ischaemic preconditioning on mobilisation and recruitment of haematopoietic and mesenchymal stem cells in porcine myocardial ischaemia-reperfusion. Thromb Haemost. 2010;104:376–84.PubMedCrossRefGoogle Scholar
  133. 133.
    Czeiger D, Dukhno O, Douvdevani A, Porat Y, Shimoni D, Fulga V, et al. Transient extremity ischemia augments CD34+ progenitor cell availability. Stem Cell Rev Rep. 2011;7:639–45.CrossRefGoogle Scholar
  134. 134.
    Patschan D, Krupincza K, Patschan S, Zhang ZT, Hamby C, Goligorsky MS. Dynamics of mobilization and homing of endothelial progenitor cells after acute renal ischemia: modulation by ischemic preconditioning. Am J Physiol Renal Physiol. 2006;291:F176–85.PubMedCrossRefGoogle Scholar
  135. 135.
    Akita T, Murohara T, Ikeda H, Sasaki KI, Shimada T, Egami K, et al. Hypoxic preconditioning augments efficacy of human endothelial progenitor cells for therapeutic neovascularization. Lab Investig. 2003;83:65–73.PubMedCrossRefGoogle Scholar
  136. 136.
    Leroux L, Descamps B, Tojais NF, Seguy B, Oses P, Moreau C, et al. Hypoxia preconditioned mesenchymal stem cells improve vascular and skeletal muscle fiber regeneration after ischemia through a Wnt4-dependent pathway. Mol Ther. 2010;18:1545–52.PubMedCrossRefGoogle Scholar
  137. 137.
    Yamazaki M, Nakamura K, Mizukami Y, Ii M, Sasajima J, Sugiyama Y, et al. Sonic hedgehog derived from human pancreatic cancer cells augments angiogenic function of endothelial progenitor cells. Cancer Sci. 2008;99:1131–8.PubMedCrossRefGoogle Scholar
  138. 138.
    Volkmer E, Kallukalam BC, Maertz J, Otto S, Drosse I, Polzer H, et al. Hypoxic preconditioning of human mesenchymal stem cells overcomes hypoxia-induced inhibition of osteogenic differentiation. Tissue Eng Part A. 2010;16:153–64.PubMedCrossRefGoogle Scholar
  139. 139.
    Morimoto D, Tomita T, Kuroda S, Higuchi C, Kato S, Shiba T, et al. Inorganic polyphosphate differentiates human mesenchymal stem cells into osteoblastic cells. J Bone Miner Metab. 2010;28:418–23.PubMedCrossRefGoogle Scholar
  140. 140.
    Kawazoe Y, Katoh S, Onodera Y, Kohgo T, Shindoh M, Shiba T. Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate. Int J Biol Sci. 2008;4:37–47.PubMedCrossRefGoogle Scholar
  141. 141.
    Shmelkov SV, Meeus S, Moussazadeh N, Kermani P, Rashbaum WK, Rabbany SY, et al. Cytokine preconditioning promotes codifferentiation of human fetal liver CD133(+) stem cells into angiomyogenic tissue. Circulation. 2005;111:1175–83.PubMedCrossRefGoogle Scholar
  142. 142.
    Cui JH, Park SR, Park K, Choi BH, Min BH. Preconditioning of mesenchymal stem cells with low-intensity ultrasound for cartilage formation in vivo. Tissue Eng. 2007;13:351–60.PubMedCrossRefGoogle Scholar
  143. 143.
    Lucchinetti E, Zeisberger SM, Baruscotti I, Wacker J, Feng JH, Zaugg K, et al. Stem cell-like human endothelial progenitors show enhanced colony-forming capacity after brief sevoflurane exposure: preconditioning of angiogenic cells by volatile anesthetics. Anesth Analg. 2009;109:1117–26.PubMedCrossRefGoogle Scholar
  144. 144.
    Popescu M, Munteanu A, Isvoranu G, Suciu L, Pavel B, Marinescu B, et al. Dynamics of endothelial progenitor cells following sevoflurane preconditioning. Roum Arch Microbiol Immunol. 2011;70:109–13.PubMedGoogle Scholar
  145. 145.
    Kubo M, Li TS, Kurazumi H, Takemoto Y, Ohshima M, Murata T, et al. Hypoxic preconditioning enhances angiogenic potential of bone marrow cells with aging-related functional impairment. Circ J. 2012;76:986–94.PubMedCrossRefGoogle Scholar
  146. 146.
    Wang MJ, Tsai BM, Crisostomo PR, Meldrum DR. Pretreatment with adult progenitor cells improves recovery and decreases native myocardial proinflammatory signaling after ischemia. Shock. 2006;25:454–9.PubMedCrossRefGoogle Scholar
  147. 147.
    Bacigaluppi M, Pluchino S, Jametti LP, Kilic E, Kilic U, Salani G, et al. Delayed post-ischaemic neuroprotection following systemic neural stem cell transplantation involves multiple mechanisms. Brain. 2009;132:2239–51.PubMedCrossRefGoogle Scholar
  148. 148.
    Loos B, Smith R, Engelbrecht AM. Ischaemic preconditioning and TNF-alpha-mediated preconditioning is associated with a differential cPLA(2) translocation pattern in early ischaemia. Prostaglandins Leukot Essent Fat Acids. 2008;78:403–13.CrossRefGoogle Scholar
  149. 149.
    Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, et al. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells. 2006;24:386–98.PubMedCrossRefGoogle Scholar
  150. 150.
    Cheng AS, Yau TM. Paracrine effects of cell transplantation: strategies to augment the efficacy of cell therapies. Sem Thorac Cardiovasc Surg. 2008;20:94–101.CrossRefGoogle Scholar
  151. 151.
    Canfield SG, Sepac A, Sedlic F, Muravyeva MY, Bai XW, Bosnjak ZJ. Marked hyperglycemia attenuates anesthetic preconditioning in human-induced pluripotent stem cell-derived cardiomyocytes. Anesthesiology. 2012;117:735–44.PubMedCrossRefGoogle Scholar
  152. 152.
    Zeng XJ, Yu SP, Zhang L, Wei L. Neuroprotective effect of the endogenous neural peptide apelin in cultured mouse cortical neurons. Exp Cell Res. 2010;316:1773–83.PubMedCrossRefGoogle Scholar
  153. 153.
    Ito T, Itakura S, Todorov I, Rawson J, Asari S, Shintaku J, et al. Mesenchymal stem cell and islet co-transplantation promotes graft revascularization and function. Transplantation. 2010;89:1438–45.PubMedCrossRefGoogle Scholar
  154. 154.
    Oh JS, Ha Y, An SS, Khan M, Pennant WA, Kim HJ, et al. 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. 2010;472:215–9.PubMedCrossRefGoogle Scholar
  155. 155.
    Kim HW, Haider HK, Jiang SJ, Ashraf M. Ischemic preconditioning augments survival of stem cells via mir-210 expression by targeting caspase-8-associated protein 2. J Biol Chem. 2009;284:33161–8.PubMedCrossRefGoogle Scholar
  156. 156.
    Noiseux N, Borie M, Desnoyers A, Menaouar A, Stevens LM, Mansour S, et al. Preconditioning of stem cells by oxytocin to improve their therapeutic potential. Endocrinology. 2012;153:5361–72.PubMedCrossRefGoogle Scholar
  157. 157.
    Chen TL, Wang JA, Shi H, Gui C, Luo RH, Xie XJ, et al. Cyclosporin A pre-incubation attenuates hypoxia/reoxygenation-induced apoptosis in mesenchymal stem cells. Scand J Clin Lab Inv. 2008;68:585–93.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of AnesthesiologyEmory University School of MedicineAtlantaUSA
  2. 2.Neuroscience Research Institute and Department of NeurobiologySchool of Basic Medical Sciences, Peking UniversityBeijingChina

Personalised recommendations