Effects of Myeloablation, Peripheral Chimerism, and Whole-Body Irradiation on the Entry of Bone Marrow-Derived Cells Into the Brain

被引:57
作者
Lampron, Antoine
Lessard, Martine
Rivest, Serge [1 ,2 ]
机构
[1] Univ Laval, Fac Med, Lab Endocrinol & Genom, CHUL Res Ctr, Quebec City, PQ G1K 7P4, Canada
[2] Univ Laval, Fac Med, Dept Mol Med, Quebec City, PQ G1K 7P4, Canada
关键词
Microglia; Central nervous sysem (CNS); Neuroimmunology; Hematopoietic stem cell; Irradiation; Chemotherapy; Bone marrow-derived cells; Innate immunity; CENTRAL-NERVOUS-SYSTEM; BARRIER PERMEABILITY; ALZHEIMERS-DISEASE; STEM-CELLS; MICROGLIA; EXPRESSION; CLONING; PLAY;
D O I
10.3727/096368911X593154
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Understanding how bone marrow-derived cells (BMDCs) enter the central nervous system (CNS) is critical for the development of therapies for brain-related disorders using hematopoietic stem cells. We investigated the brain damages and blood-brain barrier (BBB) modification following either whole-body irradiation or a myeloablative chemotherapy regimen in mice, and the capacity for these treatments to induce the entry of BMDCs into the CNS. Neither treatment had a lasting effect on brain integrity and both were equally efficient at achieving myeloablation. Injection of bone marrow cells from green fluorescent protein (GFP) transgenic mice was able to completely repopulate the hematopoietic niche in the circulation and in hematopoietic organs (thymus and spleen). However, GFP(+) cells only entered the brain following whole-body irradiation. We conclude that myeloablation, damages to the brain integrity, or the BBB and peripheral chimerism are not responsible for the entry of BMDCs into the CNS following irradiation.
引用
收藏
页码:1149 / 1159
页数:11
相关论文
共 24 条
[1]   Local self-renewal can sustain CNS microglia maintenance and function throughout adult life [J].
Ajami, Bahareh ;
Bennett, Jami L. ;
Krieger, Charles ;
Tetzlaff, Wolfram ;
Rossi, Fabio M. V. .
NATURE NEUROSCIENCE, 2007, 10 (12) :1538-1543
[2]   Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy [J].
Cartier, Nathalie ;
Hacein-Bey-Abina, Salima ;
Bartholomae, Cynthia C. ;
Veres, Gabor ;
Schmidt, Manfred ;
Kutschera, Ina ;
Vidaud, Michel ;
Abel, Ulrich ;
Dal-Cortivo, Liliane ;
Caccavelli, Laure ;
Mahlaoui, Nizar ;
Kiermer, Veronique ;
Mittelstaedt, Denice ;
Bellesme, Celine ;
Lahlou, Najiba ;
Lefrere, Francois ;
Blanche, Stephane ;
Audit, Muriel ;
Payen, Emmanuel ;
Leboulch, Philippe ;
l'Homme, Bruno ;
Bougneres, Pierre ;
Von Kalle, Christof ;
Fischer, Alain ;
Cavazzana-Calvo, Marina ;
Aubourg, Patrick .
SCIENCE, 2009, 326 (5954) :818-823
[3]   RADIATION-INDUCED APOPTOSIS - RELEVANCE TO RADIOTHERAPY [J].
DEWEY, WC ;
LING, CC ;
MEYN, RE .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1995, 33 (04) :781-796
[4]   Blood-brain barrier permeability after gamma whole-body irradiation: an in vivo microdialysis study [J].
Diserbo, M ;
Agin, A ;
Lamproglou, I ;
Mauris, J ;
Staali, F ;
Multon, E ;
Amourette, C .
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 2002, 80 (07) :670-678
[5]   Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages [J].
Ginhoux, Florent ;
Greter, Melanie ;
Leboeuf, Marylene ;
Nandi, Sayan ;
See, Peter ;
Gokhan, Solen ;
Mehler, Mark F. ;
Conway, Simon J. ;
Ng, Lai Guan ;
Stanley, E. Richard ;
Samokhvalov, Igor M. ;
Merad, Miriam .
SCIENCE, 2010, 330 (6005) :841-845
[6]   Changing Face of Microglia [J].
Graeber, Manuel B. .
SCIENCE, 2010, 330 (6005) :783-788
[7]  
GRAY PW, 1986, J IMMUNOL, V137, P3644
[8]   Mechanisms of Mononuclear Phagocyte Recruitment in Alzheimer's Disease [J].
Hickman, Suzanne E. ;
El Khoury, Joseph .
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS, 2010, 9 (02) :168-173
[9]   Cooperation between toll-like receptor 2 and 4 in the brain of mice challenged with cell wall components derived from gram-negative and gram-positive bacteria [J].
Laflamme, N ;
Echchannaoui, H ;
Landmann, R ;
Rivest, S .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2003, 33 (04) :1127-1138
[10]   Effects of systemic immunogenic insults and circulating proinflammatory cytokines on the transcription of the inhibitory factor κBα within specific cellular populations of the rat brain [J].
Laflamme, N ;
Rivest, S .
JOURNAL OF NEUROCHEMISTRY, 1999, 73 (01) :309-321