Co-transplantation of bone marrow-derived mesenchymal stem cells and nanospheres containing FGF-2 improve cell survival and neurological function in the injured rat spinal cord

被引:26
作者
Shin, Dong Ah [1 ]
Pennant, William A. [1 ]
Yoon, Do Heum [1 ,2 ]
Ha, Yoon [1 ,2 ]
Kim, Keung Nyun [1 ,2 ]
机构
[1] Yonsei Univ, Coll Med, Spine & Spinal Cord Inst, Dept Neurosurg, Seoul, South Korea
[2] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul, South Korea
关键词
Bone marrow; Mesenchymal stemcells; Nanosphere; FGF-2; Spinal cord injury; FIBROBLAST-GROWTH-FACTOR; STROMAL CELLS; LONG-TERM; RECOVERY; EXPRESSION; NEURONS; DIFFERENTIATION; NEUROGENESIS; PROGENITORS; FACTOR-2;
D O I
10.1007/s00701-013-1963-y
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Spinal cord injury (SCI) is a devastating and irreversible event, and much research using fibroblast growth factor-2 (FGF-2) has been performed to test its capacity to blunt the effects of SCI as well as to provide an environment conducive for SCI repair. We tested how the in vitro release of FGF-2 from heparin-conjugated poly(L-lactide-co-glycolide) (PLGA)-conjugated nanospheres (HCPNs) affected the growth of human bone marrow-derived mesenchymal stem cells (hBMSCs), as well as the effects of their co-transplantation in an animal model of SCI. Our results showed that sustained, long-term release of FGF-2 from HCPNs significantly increased hBMSCs proliferation in vitro, and that their co-transplantation following rat SCI lead to increased functional improvement, a greater amount of hBMSCs surviving transplantation, and a greater density of neurofilament-positive cells in the injury epicenter. These results suggest a proliferative, protective, and neural inductive potential of FGF-2 for transplanted hBMSCs, as well as a possible role for sustained FGF-2 delivery along with hBMSCs transplantation in the injured spinal cord. Future studies will be required to ascertain the safety FGF-2-containing HCPNs before clinical application.
引用
收藏
页码:297 / 303
页数:7
相关论文
共 30 条
[1]  
Akiyama Y, 2002, J NEUROSCI, V22, P6623
[2]   Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection [J].
Basso, DM ;
Beattie, MS ;
Bresnahan, JC .
EXPERIMENTAL NEUROLOGY, 1996, 139 (02) :244-256
[3]   Targeted Delivery of Nanoparticles Bearing Fibroblast Growth Factor-2 by Ultrasonic Microbubble Destruction for Therapeutic Arteriogenesis [J].
Chappell, John C. ;
Song, Ji ;
Burke, Caitlin W. ;
Klibanov, Alexander L. ;
Price, Richard J. .
SMALL, 2008, 4 (10) :1769-1777
[4]  
Cizkova D, 2006, CELL MOL NEUROBIOL, V26, P1165
[5]   Nonviral Delivery of Basic Fibroblast Growth Factor Gene to Bone Marrow Stromal Cells [J].
Clements, Basak Acan ;
Hsu, Charlie Y. M. ;
Kucharski, Cezary ;
Lin, Xiaoyue ;
Rose, Laura ;
Uludag, Hasan .
CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 2009, 467 (12) :3129-3137
[6]   Mesenchymal stem cells from rat bone marrow downregulate caspase-3-mediated apoptotic pathway after spinal cord injury in rats [J].
Dasari, Venkata Ramesh ;
Spomar, Daniel G. ;
Cady, Craig ;
Gujrati, Meena ;
Rao, Jasti S. ;
Dinh, Dzung H. .
NEUROCHEMICAL RESEARCH, 2007, 32 (12) :2080-2093
[7]   Neurotrophic factors [activity-dependent neurotrophic factor (ADNF) and basic fibroblast growth factor (bFGF)] interrupt excitotoxic neurodegenerative cascades promoted by a PS1 mutation [J].
Guo, Q ;
Sebastian, L ;
Sopher, BL ;
Miller, MW ;
Glazner, GW ;
Ware, CB ;
Martin, GM ;
Mattson, MP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (07) :4125-4130
[8]   Injectable intrathecal delivery system for localized administration of EGF and FGF-2 to the injured rat spinal cord [J].
Hamann, MCJ ;
Tator, CH ;
Shoichet, MS .
EXPERIMENTAL NEUROLOGY, 2005, 194 (01) :106-119
[9]   Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery [J].
Hofstetter, CP ;
Schwarz, EJ ;
Hess, D ;
Widenfalk, J ;
El Manira, A ;
Prockop, DJ ;
Olson, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (04) :2199-2204
[10]   ACIDIC AND BASIC FIBROBLAST GROWTH-FACTORS ENHANCE NEURITE OUTGROWTH IN CULTURED RAT SPINAL-CORD NEURONS [J].
IWASAKI, Y ;
SHIOJIMA, T ;
IKEDA, K ;
TAGAYA, N ;
KOBAYASHI, T ;
KINOSHITA, M .
NEUROLOGICAL RESEARCH, 1995, 17 (01) :70-72