Repeated mesenchymal stem cell treatment after neonatal hypoxia-ischemia has distinct effects on formation and maturation of new neurons and oligodendrocytes leading to restoration of damage, corticospinal motor tract activity, and sensorimotor function.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Cindy T J van VelthovenCobi J Heijnen

Abstract

Birth asphyxia is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. We show that a single mesenchymal stem cell treatment at 3 d (MSC-3) after neonatal hypoxia-ischemia (HI) in postnatal day 9 mice improved sensorimotor function and reduced lesion size. A second MSC treatment at 10 d after HI (MSC-3+10) further enhanced sensorimotor improvement and recovery of MAP2 and MBP (myelin basic protein) staining. Ipsilateral anterograde corticospinal tract tracing with biotinylated dextran amine (BDA) showed that HI reduced BDA labeling of the contralateral spinal cord. Only MSC-3+10 treatment partially restored contralateral spinal cord BDA staining, indicating enhanced axonal remodeling. MSC-3 enhanced formation of bromodeoxyuridine-positive neurons and oligodendrocytes. Interestingly, the second gift at day 10 did not further increase new cell formation, whereas only MSC-10 did. These findings indicate that increased positive effect of MSC-3+10 compared with MSC-3 alone is mediated via distinct pathways. We hypothesize that MSCs adapt their growth and differentiation factor production to the needs of the environment at the time of intracranial injection. Comparing the response of MSCs to in vitr...Continue Reading

Associated Clinical Trials

Citations

Mar 21, 2012·Pediatric Research·Cindy T J van VelthovenCobi J Heijnen
Mar 21, 2013·Stem Cells and Development·Paulo Henrique Rosado-de-CastroRosalia Mendez-Otero
Feb 24, 2012·British Medical Bulletin·Paul R SanbergCesar V Borlongan
Feb 23, 2013·Stem Cells Translational Medicine·Irina AizmanCasey C Case
Nov 1, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Cindy Tj van VelthovenCobi J Heijnen
Mar 1, 2012·Neurology Research International·Claire ThorntonHenrik Hagberg
Jul 17, 2013·Molecular Neurobiology·Luca BraccioliCobi J Heijnen
Nov 4, 2015·Best Practice & Research. Clinical Obstetrics & Gynaecology·Kajsa Bohlin
Sep 22, 2015·International Journal of Molecular Sciences·Brandon J DixonJohn H Zhang
Feb 15, 2014·Clinics in Perinatology·Bobbi FleissPierre Gressens
Jan 19, 2016·Seminars in Perinatology·S Alex Mitsialis, Stella Kourembanas
May 23, 2012·Lancet Neurology·Bobbi Fleiss, Pierre Gressens
Apr 24, 2012·Annals of Neurology·Laura BennetAlistair Jan Gunn
Jun 22, 2012·Annals of Neurology·Cindy T J van VelthovenCobi J Heijnen
Dec 14, 2011·Annals of Neurology·Luigi TitomanlioPierre Gressens
Mar 19, 2014·Annals of Neurology·Alexander DrobyshevskySidhartha Tan
May 23, 2015·Inflammatory Bowel Diseases·Ming LiYan-Qing Li
Dec 18, 2013·Progress in Neurobiology·Xinfeng LiuJieli Chen
Jun 19, 2014·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Feifei WangYusuke Sagara
Apr 9, 2011·Brain, Behavior, and Immunity·Cindy T J van VelthovenCobi J Heijnen
Feb 5, 2015·BioMed Research International·R Berger, S Söder
Aug 28, 2014·Frontiers in Neurology·Gabriel S Gonzales-PortilloCesar V Borlongan
Mar 29, 2014·Frontiers in Physiology·Carola Meier, Katja Rosenkranz
May 5, 2016·Neurobiology of Disease·Amara LarpthaveesarpFernando F Gonzalez
Mar 11, 2017·Scientific Reports·Keiko NakanishiYujiro Higashi

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