Advertisement

Bone Marrow Hematopoietic Stem Cell Therapy in Stroke

  • Michael Jiang
  • Ling WeiEmail author
Chapter

Abstract

Mammalian bone marrow is host to an active stem cell population with the responsibility of maintaining and replenishing a variety of high turnover cells that are vital for survival, regeneration, and support of the rest of the body. The major outputs of this hematopoietic system are the erythrocytes and platelets of the blood and the granulocytes and macrophages of the immune system. These stem cells also give rise to antibody-producing B-lymphocytes and antibody-producing T-lymphocytes that consume foreign or inflammatory substrates in the body. As all of these substituent cell types have a very limited life span, they must be constantly and consistently replenished. This rapid turnover of up to 100 billion new cells from progenitors forms the hematopoietic system (Mohammadi et al. Int J Stem Cell Res Transplant, 2014 2(02), 59–62). In recent years, bone marrow hematopoietic stem cells have drawn increasing attention for their therapeutic potential used in cell transplantation therapy for neurological disorders including stroke and traumatic brain injury. This review article is to summarize recent progress in basic and preclinical investigations on these cells including hematopoietic and mesenchymal stem cells.

Keywords

Bone marrow Hematopoietic stem cell Therapy Stroke 

References

  1. 1.
    Aggarwal R, Pompili VJ, Das H. Genetic modification of ex-vivo expanded stem cells for clinical application. Front Biosci (Landmark Edition). 2009;15:854–71.CrossRefGoogle Scholar
  2. 2.
    Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med. 2002;8(9):963–70.CrossRefPubMedGoogle Scholar
  3. 3.
    Bang OY, Lee JS, Lee PH, Lee G. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol. 2005;57(6):874–82.CrossRefPubMedGoogle Scholar
  4. 4.
    Becker AJ, McCulloch EA, Till JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. 1963.Google Scholar
  5. 5.
    Bliss T, Guzman R, Daadi M, Steinberg GK. Cell transplantation therapy for stroke. Stroke. 2007;38(2):817–26.CrossRefPubMedGoogle Scholar
  6. 6.
    Broxmeyer HE, Douglas GW, Hangoc G, Cooper S, Bard J, English D, … Boyse EA. Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc Natl Acad Sci. 1989;86(10):3828–32.Google Scholar
  7. 7.
    Broxmeyer HE, Orschell CM, Clapp DW, Hangoc G, Cooper S, Plett PA, … Campbell TB. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J Exp Med. 2005;201(8):1307–18.Google Scholar
  8. 8.
    Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98(5):1076–84.CrossRefPubMedGoogle Scholar
  9. 9.
    Castillo J, Dávalos A, Noya M. Progression of ischaemic stroke and excitotoxic amino acids. Lancet. 1997;349(9045):79–82.CrossRefPubMedGoogle Scholar
  10. 10.
    Chen J, Zhang C, Jiang H, Li Y, Zhang L, Robin A, … Chopp M. Atorvastatin induction of VEGF and BDNF promotes brain plasticity after stroke in mice. J Cereb Blood Flow Metab. 2005;25(2):281–90.Google Scholar
  11. 11.
    Chen X, Li Y, Wang L, Katakowski M, Zhang L, Chen J, … Chopp M. Ischemic rat brain extracts induce human marrow stromal cell growth factor production. Neuropathology, 2002;22(4):275–79.Google Scholar
  12. 12.
    Clarke ML, Frampton J. Hematopoietic stem cells. Regenerative medicine. Springer; 2013. p. 251–77Google Scholar
  13. 13.
    Deeg HJ, Gooley TA, Flowers ME, Sale GE, Slattery JT, Anasetti C, … Kiem H-P. Allogeneic hematopoietic stem cell transplantation for myelofibrosis. Blood. 2003;102(12):3912–18.Google Scholar
  14. 14.
    Del Zoppo G. The neurovascular unit in the setting of stroke. J Intern Med. 2010;267(2):156–71.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Domen J, Weissman IL. Self-renewal, differentiation or death: regulation and manipulation of hematopoietic stem cell fate. Mol Med Today. 1999;5(5):201–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Ehrenreich H, Weissenborn K, Prange H, Schneider D, Weimar C, Wartenberg K, … Wegrzyn M. Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke. 2009;40(12):e647–56.Google Scholar
  17. 17.
    Ekdahl C, Kokaia Z, Lindvall O. Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience. 2009;158(3):1021–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Erdö F, Bührle C, Blunk J, Hoehn M, Xia Y, Fleischmann B, … Hescheler J. Host-dependent tumorigenesis of embryonic stem cell transplantation in experimental stroke. J Cereb Blood Flow Metab. 2003;23(7):780–85.Google Scholar
  19. 19.
    Francis K, Wei L. Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning. Cell Death Dis. 2010;1(2), e22.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Frenkel D, Huang Z, Maron R, Koldzic DN, Hancock WW, Moskowitz MA, Weiner HL. Nasal vaccination with myelin oligodendrocyte glycoprotein reduces stroke size by inducing IL-10-producing CD4+ T cells. J Immunol. 2003;171(12):6549–55.CrossRefPubMedGoogle Scholar
  21. 21.
    Furlan M, Marchal G, Derlon JM, Baron JC, Viader F. Spontaneous neurological recovery after stroke and the fate of the ischemic penumbra. Ann Neurol. 1996;40(2):216–26.CrossRefPubMedGoogle Scholar
  22. 22.
    Gage FH. Mammalian neural stem cells. Science. 2000;287(5457):1433–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev. 2005;57(2):173–85.CrossRefPubMedGoogle Scholar
  24. 24.
    Henschler R, Fehervizyova Z, Bistrian R, Seifried E. A mouse model to study organ homing behaviour of haemopoietic progenitor cells reveals high selectivity but low efficiency of multipotent progenitors to home into haemopoietic organs. Br J Haematol. 2004;126(1):111–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Hess DC, Borlongan C. Stem cells and neurological diseases. Cell Prolif. 2008;41(s1):94–114.PubMedGoogle Scholar
  26. 26.
    Hill WD, Hess DC, Martin-Studdard A, Carothers JJ, Zheng J, Hale D, … Conway SJ. SDF‐1 (CXCL12) Is Upregulated in the ischemic penumbra following stroke: association with bone marrow cell homing to injury. J Neuropathol Exp Neurol. 2004;63(1):84–96.Google Scholar
  27. 27.
    Hu X, Wei L, Taylor TM, Wei J, Zhou X, Wang J-A, Yu SP. Hypoxic preconditioning enhances bone marrow mesenchymal stem cell migration via Kv2. 1 channel and FAK activation. Am J Phys Cell Phys. 2011;301(2):C362–72.CrossRefGoogle Scholar
  28. 28.
    Hu X, Yu SP, Fraser JL, Lu Z, Ogle ME, Wang J-A, Wei L. 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(4):799–808.CrossRefPubMedGoogle Scholar
  29. 29.
    Jin K, Sun Y, Xie L, Batteur S, Mao XO, Smelick C, … Greenberg DA. Neurogenesis and aging: FGF‐2 and HB‐EGF restore neurogenesis in hippocampus and subventricular zone of aged mice. Aging Cell. 2003;2(3):175–83.Google Scholar
  30. 30.
    Kamel H, Iadecola C. Brain-immune interactions and ischemic stroke: clinical implications. Arch Neurol. 2012;69(5):576–81.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci. 1999;96(19):10711–6.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Li Y, Chen J, Chen X, Wang L, Gautam S, Xu Y, … Janakiraman N. Human marrow stromal cell therapy for stroke in rat neurotrophins and functional recovery. Neurology. 2002;59(4):514–23.Google Scholar
  33. 33.
    Li Y, Chopp M, Chen J, Wang L, Gautam SC, Xu Y-X, Zhang Z. Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab. 2000;20(9):1311–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Lidman B, Cohn C. Effect of radar emmanations on the hematopoietic system. Air Surg Bull US Army Air Forces Office Air Surg. 1945;2:448.Google Scholar
  35. 35.
    Lo EH. A new penumbra: transitioning from injury into repair after stroke. Nat Med. 2008;14(5):497–500.CrossRefPubMedGoogle Scholar
  36. 36.
    Lorenz E, Congdon C, Uphoff D. Modification of acute irradiation injury in mice and Guinea-Pigs by bone marrow injections 1. Radiology. 1952;58(6):863–77.CrossRefPubMedGoogle Scholar
  37. 37.
    Matsuoka S, Tsuji K, Hisakawa H, Xu M-j, Ebihara Y, Ishii T, … Ikeda Y. Generation of definitive hematopoietic stem cells from murine early yolk sac and paraaortic splanchnopleures by aorta-gonad-mesonephros region–derived stromal cells. Blood. 2001;98(1):6–12.Google Scholar
  38. 38.
    Mohammadi H, Mohammadnejad J, Yavari K. Human peripheral blood derived hematopoietic stem cell: history, the isolation methods and investigation of different parameters effects on their differentiation to the body cells. Int J Stem Cell Res Transplant. 2014;2(02):59–62.Google Scholar
  39. 39.
    Morrison SJ, Prowse KR, Ho P, Weissman IL. Telomerase activity in hematopoietic cells is associated with self-renewal potential. Immunity. 1996;5(3):207–16.CrossRefPubMedGoogle Scholar
  40. 40.
    Morrison SJ, Wandycz AM, Akashi K, Globerson A, Weissman IL. The aging of hematopoietic stem cells. Nat Med. 1996;2(9):1011–6.CrossRefPubMedGoogle Scholar
  41. 41.
    Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, … Fullerton HJ. Heart disease and stroke statistics—2016 update a report from the American Heart Association. Circulation. 2015; CIR. 0000000000000350.Google Scholar
  42. 42.
    Ohab JJ, Fleming S, Blesch A, Carmichael ST. A neurovascular niche for neurogenesis after stroke. J Neurosci. 2006;26(50):13007–16.CrossRefPubMedGoogle Scholar
  43. 43.
    Ohneda O, Fennie C, Zheng Z, Donahue C, La H, Villacorta R, … Lasky LA. Hematopoietic stem cell maintenance and differentiation are supported by embryonic aorta-gonad-mesonephros region–derived endothelium. Blood. 1998;92(3):908–19.Google Scholar
  44. 44.
    Oki K, Tatarishvili J, Wood J, Koch P, Wattananit S, Mine Y, … Ladewig J. Human‐induced pluripotent stem cells form functional neurons and improve recovery after grafting in stroke‐damaged brain. Stem Cells. 2012;30(6):1120–133.Google Scholar
  45. 45.
    Orkin SH. Development of the hematopoietic system. Curr Opin Genet Dev. 1996;6(5):597–602.CrossRefPubMedGoogle Scholar
  46. 46.
    Pacary E, Legros H, Valable S, Duchatelle P, Lecocq M, Petit E, … Bernaudin M. Synergistic effects of CoCl2 and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells. J Cell Sci. 2006;119(13):2667–78.Google Scholar
  47. 47.
    Paczkowska E, Larysz B, Rzeuski R, Karbicka A, Jałowiński R, Kornacewicz‐Jach Z, … Machaliński B. Human hematopoietic stem/progenitor‐enriched CD34+ cells are mobilized into peripheral blood during stress related to ischemic stroke or acute myocardial infarction. Eur J Haematol. 2005;75(6):461–67.Google Scholar
  48. 48.
    Parent JM, Vexler ZS, Gong C, Derugin N, Ferriero DM. Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol. 2002;52(6):802–13.CrossRefPubMedGoogle Scholar
  49. 49.
    Parmar K, Mauch P, Vergilio J-A, Sackstein R, Down JD. Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc Natl Acad Sci. 2007;104(13):5431–6.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Plett PA, Frankovitz SM, Orschell CM. Distribution of marrow repopulating cells between bone marrow and spleen early after transplantation. Blood. 2003;102(6):2285–91.CrossRefPubMedGoogle Scholar
  51. 51.
    Recio JS, Alvarez-Dolado M, Díaz D, Baltanás FC, Piquer-Gil M, Alonso JR, Weruaga E. Bone marrow contributes simultaneously to different neural types in the central nervous system through different mechanisms of plasticity. Cell Transplant. 2011;20(8):1179–92.CrossRefPubMedGoogle Scholar
  52. 52.
    Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11.CrossRefPubMedGoogle Scholar
  53. 53.
    Ross MA, Sander CM, Kleeb TB, Watkins SC, Stolz DB. Spatiotemporal expression of angiogenesis growth factor receptors during the revascularization of regenerating rat liver. Hepatology. 2001;34(6):1135–48.CrossRefPubMedGoogle Scholar
  54. 54.
    Siena S, Bregni M, Brando B, Belli N, Ravagnani F, Gandola L, … Gianni AM. Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients. Blood. 1991;77(2):400–09.Google Scholar
  55. 55.
    Simard AR, Rivest S. Bone marrow stem cells have the ability to populate the entire central nervous system into fully differentiated parenchymal microglia. FASEB J. 2004;18(9):998–1000.PubMedGoogle Scholar
  56. 56.
    Spangrude GJ. Hematopoietic stem-cell differentiation. Curr Opin Immunol. 1991;3(2):171–8.CrossRefPubMedGoogle Scholar
  57. 57.
    Stadtmauer EA, O’Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN, … Erban JK. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Engl J Med. 2000;342(15):1069–76.Google Scholar
  58. 58.
    Su EJ, Fredriksson L, Geyer M, Folestad E, Cale J, Andrae J, … Yepes M. Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke. Nat Med. 2008;14(7):731–37.Google Scholar
  59. 59.
    Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H, … Stern DM. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model. J Clin Investig. 2004;114(3):330–38.Google Scholar
  60. 60.
    Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, … Scott EW. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature. 2002;416(6880):542–45.Google Scholar
  61. 61.
    Theus MH, Wei L, Cui L, Francis K, Hu X, Keogh C, Yu SP. 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(2):656–70.CrossRefPubMedGoogle Scholar
  62. 62.
    Toda S, Nishimura T, Yamada S, Koike N, Yonemitsu N, Watanabe K, … Sugihara H. Immunohistochemical expression of growth factors in subacute thyroiditis and their effects on thyroid folliculogenesis and angiogenesis in collagen gel matrix culture. J Pathol. 1999;188(4):415–22.Google Scholar
  63. 63.
    van Bruggen N, Thibodeaux H, Palmer JT, Lee WP, Fu L, Cairns B, … van Lookeren Campagne M. VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion injury in the mouse brain. J Clin Investig. 1999;104(11):1613–20.Google Scholar
  64. 64.
    Wang L, Li Y, Chen X, Chen J, Gautam SC, Xu Y, Chopp M. MCP-1, MIP-1, IL-8 and ischemic cerebral tissue enhance human bone marrow stromal cell migration in interface culture. Hematology. 2002;7(2):113–7.CrossRefPubMedGoogle Scholar
  65. 65.
    Weissman IL, Anderson DJ, Gage F. Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol. 2001;17(1):387–403.CrossRefPubMedGoogle Scholar
  66. 66.
    Zhang ZG, Chopp M. Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet Neurol. 2009;8(5):491–500.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Zhao L-R, Duan W-M, Reyes M, Keene CD, Verfaillie CM, Low WC. Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol. 2002;174(1):11–20.CrossRefPubMedGoogle Scholar
  68. 68.
    Zhu W, Fan Y, Frenzel T, Gasmi M, Bartus RT, Young WL, … Chen Y. Insulin growth factor-1 gene transfer enhances neurovascular remodeling and improves long-term stroke outcome in mice. Stroke. 2008;39(4):1254–61.Google Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Department of AnesthesiologyEmory University School of MedicineAtlantaUSA

Personalised recommendations