Delayed intralesional transplantation of bone marrow stromal cells increases endogenous neurogenesis and promotes functional recovery after severe traumatic brain injury

被引:65
作者
Bonilla, Celia
Zurita, Mercedes
Otero, Laura
Aguayo, Concepcion
Vaquero, Jesus [1 ]
机构
[1] Autonomous Univ Madrid, Hosp Puerta Hierro Majadahonda, Neurosci Res Unit, Madrid 28222, Spain
关键词
Stem cells; bone marrow stromal cells; brain trauma; cell therapy; MESENCHYMAL STEM-CELLS; SUBVENTRICULAR ZONE; NEURAL STEM; INTRACEREBRAL TRANSPLANTATION; NEURONAL DIFFERENTIATION; ADULT RATS; PROLIFERATION; THERAPY; STROKE; NEUROTROPHINS;
D O I
10.1080/02699050903133970
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
Primary objective: To investigate the utility of delayed transplantation of bone marrow stromal cells (BMSC) to improve the neurological sequels after traumatic brain injury (TBI). Methods: Adult Wistar rats were subjected to weight-drop impact causing severe brain injury, and 2 months later, BMSC in saline, or saline alone, were injected into injured brain tissue. Both experimental groups were evaluated by means of rotarod and modified neurologic severity scores (mNSS) tests in the course of the two following months. At this time, the animal were sacrificed and their brains were studied by means of histological and immunohistochemical techniques. Results: Rotarod and mNSS tests showed progressive functional recovery in the BMSC- transplanted rats, compared with controls. Two months after transplantation, BMSC survived in the host tissue, and some of them showed expression of Neu-N or GFAP, suggesting neuronal and astroglial transdifferentiation. Furthermore, significant increase of endogenous neurogenesis was found in BMSC-transplanted rats, compared with controls. Conclusions: These findings suggest the utility of delayed intracerebral transplantation of BMSC for the treatment of established sequels after TBI.
引用
收藏
页码:760 / 769
页数:10
相关论文
共 45 条
[1]
Cell replacement therapy for intracerebral hemorrhage [J].
Andres, Robert H. ;
Guzman, Raphael ;
Ducray, Angelique D. ;
Mordasini, Pasquale ;
Gera, Atul ;
Barth, Alain ;
Widmer, Hans R. ;
Steinberg, Gary K. .
NEUROSURGICAL FOCUS, 2008, 24 (3-4)
[2]
Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat [J].
Chen, JL ;
Li, Y ;
Katakowski, M ;
Chen, XG ;
Wang, L ;
Lu, DY ;
Lu, M ;
Gautam, SC ;
Chopp, M .
JOURNAL OF NEUROSCIENCE RESEARCH, 2003, 73 (06) :778-786
[3]
Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats [J].
Chen, JL ;
Li, Y ;
Wang, L ;
Lu, M ;
Zhang, XH ;
Chopp, M .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2001, 189 (1-2) :49-57
[4]
Human bone marrow stromal cell cultures conditioned by traumatic brain tissue extracts: Growth factor production [J].
Chen, XG ;
Katakowski, M ;
Li, Y ;
Lu, DY ;
Wang, L ;
Zhang, LJ ;
Chen, JL ;
Xu, YX ;
Gautam, S ;
Mahmood, A ;
Chopp, M .
JOURNAL OF NEUROSCIENCE RESEARCH, 2002, 69 (05) :687-691
[5]
Neurogenesis and glial proliferation persist for at least one year in the subventricular zone following brain trauma in rats [J].
Chen, XH ;
Iwata, A ;
Nonaka, M ;
Browne, KD ;
Smith, DH .
JOURNAL OF NEUROTRAUMA, 2003, 20 (07) :623-631
[6]
Treatment of neural injury with marrow stromal cells [J].
Chopp, M ;
Li, Y .
LANCET NEUROLOGY, 2002, 1 (02) :92-100
[7]
GARCIACASTRO J, 2008, CELL THERAPY, P58
[8]
Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms [J].
Kinnaird, T ;
Stabile, E ;
Burnett, MS ;
Shou, M ;
Lee, CW ;
Barr, S ;
Fuchs, S ;
Epstein, SE .
CIRCULATION, 2004, 109 (12) :1543-1549
[9]
Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains [J].
Kopen, GC ;
Prockop, DJ ;
Phinney, DG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (19) :10711-10716
[10]
Expression of neurotrophins and their receptors in human bone marrow [J].
Labouyrie, E ;
Dubus, P ;
Groppi, A ;
Mahon, FX ;
Ferrer, J ;
Parrens, M ;
Reiffers, J ;
de Mascarel, A ;
Merlio, JP .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 154 (02) :405-415