Journal of Neurology

, Volume 254, Issue 3, pp 327–332 | Cite as

Neurological and functional recovery in human stroke are associated with peripheral blood CD34+ cell mobilization

  • Antoine Dunac
  • Christian Frelin
  • Margherita Popolo-Blondeau
  • Marcel Chatel
  • Marie H. Mahagne
  • Patrick J.-M. Philip
ORIGINAL COMMUNICATION

Abstract

Background

A spontaneous mobilization of Peripheral Blood-Mononuclear CD34+ Cells (PB-MNC-CD34+) has recently been reported in human myocardial infarction and found to be related to improved heart function and survival. However, nothing is known regarding a possible relation between PB-MNC-CD34+ mobilization and neurological recovery in human acute cerebral ischemia.

Methods and Results

PB-MNC-CD34+ were determined daily after an acute cerebral ischemic attack for 14 days in 25 patients with acute ischemic stroke and compared with controls. Results indicated that stroke was followed by large and bursting mobilizations of PB-MNC-CD34+. The amplitude of the mobilizations was similar to those observed in Granulocyte Colony Stimulating Factor (G-CSF) conditioned aplastic patients following myeloablative therapy before leukapheresis and autologous bone graft. The extent of PB-MNC-CD34+ mobilization in each patient was directly related to neurological and functional recoveries as assessed by NIH Stroke Scale, and modified Rankin Scale respectively.

Conclusions

The mobilization of PB-MNC-CD34+ cells might be predictive of neurological and functional recovery.

Keywords

angiogenesis neurological recovery functional recovery stem cell plasticity stroke 

Notes

Acknowledgement

Authors are very thankful to: Dr Frederic Berthier (from the “Département d’Information Médicale, CHU de Nice) for his valuable contribution in biostatistics; Mr Julien Nivet, Clinical Research Associate; the National Institute of Science and Medical Research and the University Hospital of Nice. We are also very thankful to the “UEFCT’s technicians”.

References

  1. 1.
    Abkowitz J (2002) Can Human Hematopoietic Stem Cells Become Skin, Gut, or Liver Cells? N Engl J Med 346:770–772PubMedCrossRefGoogle Scholar
  2. 2.
    Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85:221–228PubMedGoogle Scholar
  3. 3.
    Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischemic myocardium. Nature 428:668–673PubMedCrossRefGoogle Scholar
  4. 4.
    Bautch VL, Redick SD, Scalia A, Harmaty M, Carmeliet P, Rapoport R (2000) Characterisation of the vasculogenic block in the absence of vascular endothelial growth factor-A. Blood 95:1979–1987PubMedGoogle Scholar
  5. 5.
    Dunac A, Frelin C, Mahagne MH, Chatel M, Philip PJM (2002) Mobilization of CD34+ progenitor cells during recovery in acute ischemic stroke: a new mechanism for cerebral ischemic tissue repair. J Neurol 249: (S1) I/31Google Scholar
  6. 6.
    Egusa Y, Fujiwara Y, Syahruddin E, Isobe T, Yamakido M (1998) Effect of age on human, peripheral blood stem cells. Oncol. Rep 5:397–400PubMedGoogle Scholar
  7. 7.
    Hess DC, Hill WD, Martin-Studdard A, Carroll J, Brailer J, Carothers J (2002) Bone marrow as source of endothelial cells and NeuN-expressing cells after stroke. Stroke 33:1362–1368PubMedCrossRefGoogle Scholar
  8. 8.
    Jeong SW, Chu K, Jung KH, Kim SU, Kim M, Roh JK (2003) Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage. Stroke 34:2258–2263PubMedCrossRefGoogle Scholar
  9. 9.
    Kashiwakura Y, Katoh Y, Tamayose K, Konishi H, Takaya N, Yuhara S, Sugimoto K, Daida H (2003) Isolation of bone marrow stromal cell-derived smooth muscle cells by a human SM22a promoter. Circulation 107:2078PubMedCrossRefGoogle Scholar
  10. 10.
    Kim B, Seo JH, Bubien JK, Oh YS (2002) Differentiation of adult bone marrow stem cells into neuroprogenitor cells in vitro. Neuroreport 13:1185–1188PubMedCrossRefGoogle Scholar
  11. 11.
    Li Y, Chen J, Chen XG (2002) Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery. Neurology 59:486–487CrossRefGoogle Scholar
  12. 12.
    Li Y, Chen J, Wang L, Lu M, Chopp M (2001) Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology 56:1666–1672PubMedGoogle Scholar
  13. 13.
    Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J, Sano M, Takahashi T, Hori S, Abe H, Hata J, Umezawa A, Ogawa S (1999) Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest 103:687–705CrossRefGoogle Scholar
  14. 14.
    Meehan KR, Slack R, Gehan E, Herscowitz HB, Areman EM, Ebadi M, Cairo MS, Lippman ME (2002) Mobilization of peripheral blood stem cells with paclitaxel and rhG-CSF in high-risk breast cancer patients. J Hematother Stem Cell Res 2:415–21CrossRefGoogle Scholar
  15. 15.
    Misao Y, Arai M, Ohno T, Ushikoshi H, Takahashi T, Takemura G, Minatoguchi S, Fujiwara T, Fujiwara H (2005) Cyclophosphamide improves the function of post-infarct hearts by reducing old infarct area and accelerating the mobilization of CD34+ cells. Circ J 69(6):763–5PubMedCrossRefGoogle Scholar
  16. 16.
    Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, Pasumarthi KB, Virag JI, Bartelmez SH, Poppa V, Bradford G, Dowell JD, Williams DA, Field LJ (2004) Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428:664–668PubMedCrossRefGoogle Scholar
  17. 17.
    Nakul-Aquaronne D, Bayle J, Frelin C (2003) Coexpression of endothelial marker and CD14 by cytokine mobilized CD34+ cells under angiogenic stimulation. Cardiovasc Res 57:816–823PubMedCrossRefGoogle Scholar
  18. 18.
    Nygren JM, Jovinge S, Breitbach M, Sawen P, Roll W, Hescheler J, Taneera J, Fleischmann BK, Jacobsen SEW (2004) Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med 10:494–501PubMedCrossRefGoogle Scholar
  19. 19.
    Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Mobilized bone marrow repair of the infracted heart improving function and survival. Proc Natl Acad Sci USA 98:10344 –10349PubMedCrossRefGoogle Scholar
  20. 20.
    Paczkowska E, Larysz B, Rzeuski R, Karbicka A, Jałowinski R, Kornacewicz-Jach Z, Ratajczak MZ, Machalinski B (2005) 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 75:461–467PubMedCrossRefGoogle Scholar
  21. 21.
    Rempe DA, Kent T (2002) A Using bone marrow stromal cells for treatment of stroke. Neurology 59:486–487PubMedCrossRefGoogle Scholar
  22. 22.
    Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, Verfaillie CM (2002) Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest 109:337–346PubMedCrossRefGoogle Scholar
  23. 23.
    Schmidt-Lucke, Rössig L, Fichtlscherer S, Vasa M, Britten M, Kämper U, Dimmeler S, Zeiher AM (2005) Reduced Number of Circulating Endothelial Progenitor Cells Predicts Future Cardiovascular Events. Circulation 111:2981–2987PubMedCrossRefGoogle Scholar
  24. 24.
    Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A, Sasaki K, Shimada T, Oike Y, Imaizumi T (2001) Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 103:2776–2779PubMedGoogle Scholar
  25. 25.
    Slevin M, Krupinski J, Slowik A, Kumar P, Szczudlik A, Gaffney J (2000) Serial measurement of vascular endothelial growth factor and transforming growth factor-Beta-1 in serum of patients with acute ischemic stroke. Stroke 31:1863–1870PubMedGoogle Scholar
  26. 26.
    Taguchi A, Matsuyama T, Moriwaki H, Hayashi T, Hayashida K, Nagatsuka K, Todo K, Mori K, Stern DM, Soma T, Naritomi H (2004) Circulating CD34–positive cells provide an index of cerebrovascular function. Circulation 109:2972–2975PubMedCrossRefGoogle Scholar
  27. 27.
    Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H, Tsukamoto Y, Iso H, Fujimori Y, Stern DM, Naritomi H, Matsuyama T (2004) Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest 114:330–338PubMedCrossRefGoogle Scholar
  28. 28.
    Takagi Y, Nozaki K, Takahashi J, Yodoi J, Ishikawa M, Hashimoto N (1999) Proliferation of neuronal precursor cells in the dentate gyrus is accelerated after transient forebrain ischemia in mice. Brain Res 831:283–287PubMedCrossRefGoogle Scholar
  29. 29.
    Wang Y, Tägil K, Ripa RS, Nilsson JC, Carstensen S, JØrgensen E, SØndergaard L, Hesse B, Johnsen HE, Kastrup J (2005) Effect of mobilization of bone marrow stem cells by granulocyte colony stimulating factor on clinical symptoms, left ventricular perfusion and function in patients with severe chronic ischemic heart disease. Inter J Cardiol 100:477–483CrossRefGoogle Scholar
  30. 30.
    Yu J, Leisenring W, Bensinger WI, Holmberg LA, Rowley SD (1999) The predictive value of white cell or CD34 cell counts in the peripheral blood for timing apheresis and maximizing yield. Transplantation 39:442–450Google Scholar
  31. 31.
    Zhang ZG, Zhang L, Jiang Q, Chopp M (2002) Bone Marrow derived endothelial progenitor cells participate in cerebral vascularization after focal cerebral ischemia in the adult mouse. Cir Res 90:284–288CrossRefGoogle Scholar
  32. 32.
    Zhao Y, Glesne D, Huberman E (2003) A human peripheral blood monocyte-derived subset acts as pluripotent stem cells. Proc Natl Acad Sc USA 100:2426–2431PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff Verlag Darmstadt 2007

Authors and Affiliations

  • Antoine Dunac
    • 1
    • 2
    • 3
  • Christian Frelin
    • 2
    • 4
  • Margherita Popolo-Blondeau
    • 3
  • Marcel Chatel
    • 2
    • 3
  • Marie H. Mahagne
    • 2
    • 3
  • Patrick J.-M. Philip
    • 2
    • 3
    • 5
  1. 1.Dept. of Neurology (Stroke Unit)University Hospital PasteurNice CedexFrance
  2. 2.NiceFrance
  3. 3.CHRU Nice, Service de Neurologie, Stroke unitNiceFrance
  4. 4.Université de Nice Sophia AntipolisFrance
  5. 5.Dept. d’hématologieCHRU Nice, Unité d’Exploration Fonctionnelle, Cellulaire et Tissulaire (UEFCT)NiceFrance

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