Top

Published in:

01-03-2007 | ORIGINAL COMMUNICATION

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

Authors: Antoine Dunac, MD, Christian Frelin, MD, PhD, Margherita Popolo-Blondeau, MD, PhD, Marcel Chatel, MD, PhD, Marie H. Mahagne, MD, PhD, Patrick J.-M. Philip, MD

Published in: Journal of Neurology | Issue 3/2007

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.

Abkowitz J (2002) Can Human Hematopoietic Stem Cells Become Skin, Gut, or Liver Cells? N Engl J Med 346:770–772PubMedCrossRef

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 85:221–228PubMed

Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischemic myocardium. Nature 428:668–673PubMedCrossRef

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 95:1979–1987PubMed

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/31

Egusa Y, Fujiwara Y, Syahruddin E, Isobe T, Yamakido M (1998) Effect of age on human, peripheral blood stem cells. Oncol. Rep 5:397–400PubMed

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 33:1362–1368PubMedCrossRef

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 34:2258–2263PubMedCrossRef

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 107:2078PubMedCrossRef

10.

Kim B, Seo JH, Bubien JK, Oh YS (2002) Differentiation of adult bone marrow stem cells into neuroprogenitor cells in vitro. Neuroreport 13:1185–1188PubMedCrossRef

11.

Li Y, Chen J, Chen XG (2002) Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery. Neurology 59:486–487CrossRef

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 56:1666–1672PubMed

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 103:687–705CrossRef

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 2:415–21CrossRef

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):763–5PubMedCrossRef

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 428:664–668PubMedCrossRef

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 57:816–823PubMedCrossRef

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 10:494–501PubMedCrossRef

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 –10349PubMedCrossRef

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 75:461–467PubMedCrossRef

21.

Rempe DA, Kent T (2002) A Using bone marrow stromal cells for treatment of stroke. Neurology 59:486–487PubMedCrossRef

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 109:337–346PubMedCrossRef

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 111:2981–2987PubMedCrossRef

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 103:2776–2779PubMed

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 31:1863–1870PubMed

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 109:2972–2975PubMedCrossRef

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 114:330–338PubMedCrossRef

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 831:283–287PubMedCrossRef

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 100:477–483CrossRef

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 39:442–450

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 90:284–288CrossRef

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 100:2426–2431PubMedCrossRef

Title: Neurological and functional recovery in human stroke are associated with peripheral blood CD34+ cell mobilization
Authors: Antoine Dunac, MD
Christian Frelin, MD, PhD
Margherita Popolo-Blondeau, MD, PhD
Marcel Chatel, MD, PhD
Marie H. Mahagne, MD, PhD
Patrick J.-M. Philip, MD
Publication date: 01-03-2007
Publisher: Steinkopff-Verlag
Published in: Journal of Neurology / Issue 3/2007
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-006-0362-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods and Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods and Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2007

Strategies for achieving and monitoring myelin repair

Increased sensory thresholds in a patient with Ross syndrome

News in neuro-oncology: improvement of the treatment of glioblastoma and a new clinically important paraneoplastic syndrome

ENS COMMUNICATIONS

Polymorphisms in the neuromyelitis optica auto-antigen AQP4 and susceptibility to multiple sclerosis

Luigi Rolando (1773–1831)