Intra-brain microinjection of human mesenchymal stem cells decreases allodynia in neuropathic mice

被引:95
作者
Siniscalco, Dario [1 ]
Giordano, Catia [1 ]
Galderisi, Umberto [2 ]
Luongo, Livio [1 ]
Alessio, Nicola [2 ,3 ]
Di Bernardo, Giovanni [2 ]
de Novellis, Vito [1 ]
Rossi, Francesco [1 ]
Maione, Sabatino [1 ]
机构
[1] Univ Naples 2, Dept Expt Med, Div Pharmacol L Donatelli, I-80138 Naples, Italy
[2] Univ Naples 2, Dept Expt Med, Div Biotechnol & Mol Biol A Cascino, I-80138 Naples, Italy
[3] Univ Sassari, I-07100 Sassari, Italy
关键词
Neuropathic pain; Human mesenchymal stem cells; Stem cell transplantation; Regenerative medicine; MARROW STROMAL CELLS; SPARED NERVE INJURY; SPINAL-CORD-INJURY; DORSAL-HORN; SUBVENTRICULAR ZONE; OVER-EXPRESSION; APOPTOTIC GENES; RAT-BRAIN; PAIN; MECHANISMS;
D O I
10.1007/s00018-009-0202-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Neuropathic pain is a very complex disease, involving several molecular pathways. Current available drugs are usually not acting on the several mechanisms underlying the generation and propagation of pain. We used spared nerve injury model of neuropathic pain to assess the possible use of human mesenchymal stem cells (hMSCs) as anti-neuropathic tool. Human MSCs were transplanted in the mouse lateral cerebral ventricle. Stem cells injection was performed 4 days after sciatic nerve surgery. Neuropathic mice were monitored 7, 10, 14, 17, and 21 days after surgery. hMSCs were able to reduce pain-like behaviors, such as mechanical allodynia and thermal hyperalgesia, once transplanted in cerebral ventricle. Anti-nociceptive effect was detectable from day 10 after surgery (6 days post cell injection). Human MSCs reduced the mRNA levels of the pro-inflammatory interleukin IL-1 beta mouse gene, as well as the neural beta-galactosidase over-activation in prefrontal cortex of SNI mice. Transplanted hMSCs were able to reduce astrocytic and microglial cell activation.
引用
收藏
页码:655 / 669
页数:15
相关论文
共 75 条
[1]
Expression of IL-1β in supraspinal brain regions in rats with neuropathic pain [J].
Apkarian, A. Vania ;
Lavarello, Simona ;
Randolf, Anke ;
Berra, Hector H. ;
Chialvo, Dante R. ;
Besedovsky, Hugo O. ;
del Rey, Adriana .
NEUROSCIENCE LETTERS, 2006, 407 (02) :176-181
[2]
Chronic back pain is associated with decreased prefrontal and thalamic gray matter density [J].
Apkarian, AV ;
Sosa, Y ;
Sonty, S ;
Levy, RM ;
Harden, RN ;
Parrish, TB ;
Gitelman, DR .
JOURNAL OF NEUROSCIENCE, 2004, 24 (46) :10410-10415
[3]
Bone marrow-derived mesenchymal stem cells promote neuronal networks with functional synaptic transmission after transplantation into mice with neurodegeneration [J].
Bae, Jae-Sung ;
Han, Hyung Soo ;
Youn, Dong-Ho ;
Carter, Janet E. ;
Modo, Michel ;
Schuchman, Edward H. ;
Jin, Hee Kyung .
STEM CELLS, 2007, 25 (05) :1307-1316
[4]
Immunologic consequences of multiple, high-dose administration of allogeneic mesenchymal stem cells to baboons [J].
Beggs, Kirstin J. ;
Lyubimov, Alex ;
Borneman, Jade N. ;
Bartholomew, Amelia ;
Moseley, Annemarie ;
Dodds, Robert ;
Archambault, Michael P. ;
Smith, Alan K. ;
McIntosh, Kevin R. .
CELL TRANSPLANTATION, 2006, 15 (8-9) :711-721
[5]
Circumventricular organs: A novel site of neural stem cells in the adult brain [J].
Bennett, Lori ;
Yang, Ming ;
Enikolopov, Grigori ;
Lacovitti, Lorraine .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2009, 41 (03) :337-347
[6]
Beyer Nardi N, 2006, HANDB EXP PHARM, V174, P249
[7]
Bianchi M, 1998, J NEUROSCI RES, V53, P645, DOI 10.1002/(SICI)1097-4547(19980915)53:6<645::AID-JNR2>3.0.CO
[8]
2-5
[9]
Fifteen minutes of left prefrontal repetitive transcranial magnetic stimulation acutely increases thermal pain thresholds in healthy adults [J].
Borckardt, Jeffrey J. ;
Smith, Arthur R. ;
Reeves, Scott T. ;
Weinstein, Mitchell ;
Kozel, F. Andrew ;
Nahas, Ziad ;
Shelley, Neal ;
Branham, R. Kyle ;
Thomas, K. Jackson ;
George, Mark S. .
PAIN RESEARCH & MANAGEMENT, 2007, 12 (04) :287-290
[10]
Assessment and analysis of mechanical allodynia-like behavior induced by spared nerve injury (SNI) in the mouse [J].
Bourquin, Anne-Frederique ;
Sueveges, Maria ;
Pertin, Marie ;
Gilliard, Nicolas ;
Sardy, Sylvain ;
Davison, Anthony C. ;
Spahn, Donat R. ;
Decosterd, Isabelle .
PAIN, 2006, 122 (1-2) :14-16