Isolation of an adult blood-derived progenitor cell population capable of differentiation into angiogenic, myocardial and neural lineages

被引:35
作者
Porat, Yael
Porozov, Svetlana
Belkin, Danny
Shimoni, Daphna
Fisher, Yehudit
Belleli, Adina
Czeiger, David
Silverman, William F.
Belkin, Michael
Battler, Alexander
Fulga, Valentin
Savion, Naphtali
机构
[1] TheraVitae Ltd, IL-74140 Ness Ziona, Israel
[2] TheraVitae Ltd, Bangkok, Thailand
[3] Ben Gurion Univ Negev, Fac Hlth Sci, IL-84105 Beer Sheva, Israel
[4] Ben Gurion Univ Negev, Zlotowski Ctr Neurosci, IL-84105 Beer Sheva, Israel
[5] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel
关键词
stem cells; progenitor cells; cell culture; cell therapy; differentiation;
D O I
10.1111/j.1365-2141.2006.06344.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Blood-derived adult stem cells were previously considered impractical for therapeutic use because of their small numbers. This report describes the isolation of a novel human cell population derived from the peripheral blood, termed synergetic cell population (SCP), and defined by the expression of CD31(Bright), CD34(+), CD45(-/Dim) and CD34(Bright), but not lineage-specific features. The SCP was capable of differentiating into a variety of cell lineages upon exposure to defined culture conditions. The resulting cells exhibited morphological, immunocytochemical and functional characteristics of angiogenic, neural or myocardial lineages. Angiogenic cell precursors (ACPs) expressed CD34, CD133, KDR, Tie-2, CD144, von Willebrand factor, CD31(Bright), concomitant binding of Ulex-Lectin and uptake of acetylated low density lipoprotein (Ac-LDL), secreted interleukin-8, vascular endothelial growth factor and angiogenin and formed tube-like structures in vitro. The majority of CD31(Bright) ACP cells demonstrated Ac-LDL uptake. Neural cell precursors (NCPs) expressed the neuronal markers Nestin, beta III-Tubulin, and Neu-N, the glial markers GFAP and O4, and responded to neurotransmitter stimulation. Myocardial cell precursors (MCPs) expressed Desmin, cardiac Troponin and Connexin 43. In conclusion, the simple and rapid method of SCP generation and the resulting considerable quantities of lineage-specific precursor cells makes it a potential source of autologous treatment for a variety of diseases.
引用
收藏
页码:703 / 714
页数:12
相关论文
共 49 条
[1]   Induction of stem cell-like plasticity in mononuclear cells derived from unmobilised adult human peripheral blood [J].
Abuljadayel, HS .
CURRENT MEDICAL RESEARCH AND OPINION, 2003, 19 (05) :355-375
[2]   Isolation of putative progenitor endothelial cells for angiogenesis [J].
Asahara, T ;
Murohara, T ;
Sullivan, A ;
Silver, M ;
vanderZee, R ;
Li, T ;
Witzenbichler, B ;
Schatteman, G ;
Isner, JM .
SCIENCE, 1997, 275 (5302) :964-967
[3]   Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction -: (TOPCARE-AMI) [J].
Assmus, B ;
Schächinger, V ;
Teupe, C ;
Britten, M ;
Lehmann, R ;
Döbert, N ;
Grünwald, F ;
Aicher, A ;
Urbich, C ;
Martin, H ;
Hoelzer, D ;
Dimmeler, S ;
Zeiher, AM .
CIRCULATION, 2002, 106 (24) :3009-3017
[4]   Transdifferentiation of blood-derived human adult endothelial progenitor cells into functionally active cardiomyocytes [J].
Badorff, C ;
Brandes, RP ;
Popp, R ;
Rupp, S ;
Urbich, C ;
Aicher, A ;
Fleming, I ;
Busse, R ;
Zeiher, A ;
Dimmeler, S .
CIRCULATION, 2003, 107 (07) :1024-1032
[5]   Stem cells in tissue engineering [J].
Bianco, P ;
Robey, PG .
NATURE, 2001, 414 (6859) :118-121
[6]   Transplantation of progenitor cells after reperfused acute myocardial infarction:: evaluation of perfusion and myocardial viability with FDG-PET and thalliurn SPECT [J].
Döbert, N ;
Britten, M ;
Assmus, B ;
Berner, U ;
Menzel, C ;
Lehmann, R ;
Hamscho, N ;
Schächinger, V ;
Dimmeler, S ;
Zeiher, AM ;
Grünwald, F .
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2004, 31 (08) :1146-1151
[7]   Adult stem cell plasticity: new pathways of tissue regeneration become visible [J].
Forbes, SJ ;
Vig, P ;
Poulsom, R ;
Wright, NA ;
Alison, MR .
CLINICAL SCIENCE, 2002, 103 (04) :355-369
[8]   Stem cells: A new lease on life [J].
Fuchs, E ;
Segre, JA .
CELL, 2000, 100 (01) :143-155
[9]   Hematopoietic progenitors express neural genes [J].
Goolsby, J ;
Marty, MC ;
Heletz, D ;
Chiappelli, J ;
Tashko, G ;
Yarnell, D ;
Fishman, PS ;
Dhib-Jalbut, S ;
Bever, CT ;
Pessac, B ;
Trisler, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (25) :14926-14931
[10]   The role of stem cells in skeletal and cardiac muscle repair [J].
Grounds, MD ;
White, JD ;
Rosenthal, N ;
Bogoyevitch, MA .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2002, 50 (05) :589-610