Human Mesenchymal Stem Cells Prevent Neurological Complications of Radiotherapy

被引:54
作者
Soria, Bernat [1 ,2 ]
Martin-Montalvo, Alejandro [1 ]
Aguilera, Yolanda [1 ]
Mellado-Damas, Nuria [1 ]
Lopez-Beas, Javier [1 ]
Herrera-Herrera, Isabel [3 ]
Lopez, Escarlata [4 ]
Barcia, Juan A. [5 ]
Alvarez-Dolado, Manuel [1 ]
Hmadcha, Abdelkrim [1 ,2 ]
Capilla-Gonzalez, Vivian [1 ]
机构
[1] Univ Seville, Univ Pablo de Olavide, CSIC, Dept Regenerat & Cell Therapy,Andalusian Ctr Mol, Seville, Spain
[2] Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain
[3] Hosp Univ Fdn Jimenez Diaz, Dept Neuroradiol, Madrid, Spain
[4] Hosp Univ Fdn Jimenez Diaz, Dept Radiat Oncol, Madrid, Spain
[5] Univ Complutense Madrid, Serv Neurosurg, Hosp Clin San Carlos, Inst Invest Sanitaria San Carlos IdISSC,Dept Surg, Madrid, Spain
关键词
radiotherapy; stem cells; cognition; neuroprotection; intranasal cell delivery; CREB; neurocognitive sequelae; brain cancer; SUBVENTRICULAR ZONE; BEHAVIORAL DEFICITS; IN-VIVO; BRAIN; TRANSPLANTATION; IMPAIRMENT; IRRADIATION; PROTECTS; DELIVERY; GLIOSIS;
D O I
10.3389/fncel.2019.00204
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Radiotherapy is a highly effective tool for the treatment of brain cancer. However, radiation also causes detrimental effects in the healthy tissue, leading to neurocognitive sequelae that compromise the quality of life of brain cancer patients. Despite the recognition of this serious complication, no satisfactory solutions exist at present. Here we investigated the effects of intranasal administration of human mesenchymal stem cells (hMSCs) as a neuroprotective strategy for cranial radiation in mice. Our results demonstrated that intranasally delivered hMSCs promote radiation-induced brain injury repair, improving neurological function. This intervention confers protection against inflammation, oxidative stress, and neuronal loss. hMSC administration reduces persistent activation of damage-induced c-AMP response element-binding signaling in irradiated brains. Furthermore, hMSC treatment did not compromise the survival of glioma-bearing mice. Our findings encourage the therapeutic use of hMSCs as a non-invasive approach to prevent neurological complications of radiotherapy, improving the quality of life of brain tumor patients.
引用
收藏
页数:14
相关论文
共 53 条
[1]   The immune boundaries for stem cell based therapies: problems and prospective solutions [J].
Abdelkrim, Hmadcha ;
Juan, Dominguez-Bendala ;
Jane, Wakeman ;
Mohamed, Arredouani ;
Bernat, Soria .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2009, 13 (8A) :1464-1475
[2]   Subventricular Zone Localized Irradiation Affects the Generation of Proliferating Neural Precursor Cells and the Migration of Neuroblasts [J].
Achanta, Pragathi ;
Capilla-Gonzalez, Vivian ;
Purger, David ;
Reyes, Juvenal ;
Sailor, Kurt ;
Song, Hongjun ;
Manuel Garcia-Verdugo, Jose ;
Gonzalez-Perez, Oscar ;
Ford, Eric ;
Quinones-Hinojosa, Alfredo .
STEM CELLS, 2012, 30 (11) :2548-2560
[3]   Elimination of microglia improves cognitive function following cranial irradiation [J].
Acharya, Munjal M. ;
Green, Kim N. ;
Allen, Barrett D. ;
Najafi, Allison R. ;
Syage, Amber ;
Minasyan, Harutyun ;
Le, Mi T. ;
Kawashita, Takumi ;
Giedzinski, Erich ;
Parihar, Vipan K. ;
West, Brian L. ;
Baulch, Janet E. ;
Limoli, Charles L. .
SCIENTIFIC REPORTS, 2016, 6
[4]   Human Neural Stem Cell Transplantation Provides Long-Term Restoration of Neuronal Plasticity in the Irradiated Hippocampus [J].
Acharya, Munjal M. ;
Rosi, Susanna ;
Jopson, Timothy ;
Limoli, Charles L. .
CELL TRANSPLANTATION, 2015, 24 (04) :691-702
[5]   Human Neural Stem Cell Transplantation Ameliorates Radiation-Induced Cognitive Dysfunction [J].
Acharya, Munjal M. ;
Christie, Lori-Ann ;
Lan, Mary L. ;
Giedzinski, Erich ;
Fike, John R. ;
Rosi, Susanna ;
Limoli, Charles L. .
CANCER RESEARCH, 2011, 71 (14) :4834-4845
[6]   Rescue of radiation-induced cognitive impairment through cranial transplantation of human embryonic stem cells [J].
Acharya, Munjal M. ;
Christie, Lori-Ann ;
Lan, Mary L. ;
Donovan, Peter J. ;
Cotman, Carl W. ;
Fike, John R. ;
Limoli, Charles L. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (45) :19150-19155
[7]   Cognitive disability in adult patients with brain tumors [J].
Ali, Faisal S. ;
Hussain, Maryam R. ;
Gutierrez, Carolina ;
Demireva, Petya ;
Ballester, Leomar Y. ;
Zhu, Jiguang-Jay ;
Blanco, Angel ;
Esquenazi, Yoshua .
CANCER TREATMENT REVIEWS, 2018, 65 :33-40
[8]   Evaluation of Memory Impairment in Aging Adult Survivors of Childhood Acute Lymphoblastic Leukemia Treated With Cranial Radiotherapy [J].
Armstrong, Gregory T. ;
Reddick, Wilburn E. ;
Petersen, Ronald C. ;
Santucci, Aimee ;
Zhang, Nan ;
Srivastava, Deokumar ;
Ogg, Robert J. ;
Hillenbrand, Claudia M. ;
Sabin, Noah ;
Krasin, Matthew J. ;
Kun, Larry ;
Pui, Ching-Hon ;
Hudson, Melissa M. ;
Robison, Leslie L. ;
Krull, Kevin R. .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2013, 105 (12) :899-907
[9]   Intranasal Delivery of Mesenchymal Stem Cells Significantly Extends Survival of Irradiated Mice with Experimental Brain Tumors [J].
Balyasnikova, Irina V. ;
Prasol, Melanie S. ;
Ferguson, Sherise D. ;
Han, Yu ;
Ahmed, Atique U. ;
Gutova, Margarita ;
Tobias, Alex L. ;
Mustafi, Devkumar ;
Rincon, Esther ;
Zhang, Lingjiao ;
Aboody, Karen S. ;
Lesniak, Maciej S. .
MOLECULAR THERAPY, 2014, 22 (01) :140-148
[10]   Vascular damage after fractionated whole-brain irradiation in rats [J].
Brown, WR ;
Thore, CR ;
Moody, DM ;
Robbins, ME ;
Wheeler, KT .
RADIATION RESEARCH, 2005, 164 (05) :662-668