{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:42:42Z","timestamp":1790754162707,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perinatal hypoxia-ischemia (HI) is a major cause of striatal injury. Delayed post-treatment with adult-sourced bone marrow-derived mesenchymal stem cells (BMSCs) increased the absolute number of striatal medium-spiny neurons (MSNs) following perinatal HI-induced brain injury. Yet extraction of BMSCs is more invasive and difficult compared to extraction of adipose-derived mesenchymal stem cells (AD-MSCs), which are easily sourced from subcutaneous tissue. Adult-sourced AD-MSCs are also superior to BMSCs in the treatment of adult ischemic stroke. Therefore, we investigated whether delayed post-treatment with adult-sourced AD-MSCs increased the absolute number of striatal MSNs following perinatal HI-induced brain injury. This included investigation of the location of injected AD-MSCs within the brain, which were widespread in the dorsolateral subventricular zone (dlSVZ) at 1 day after their injection. Cells extracted from adult rat tissue were verified to be stem cells by their adherence to tissue culture plastic and their expression of specific \u2018cluster of differentiation\u2019 (CD) markers. They were verified to be AD-MSCs by their ability to differentiate into adipocytes and osteocytes in vitro. Postnatal day (PN) 7\/8, male Sprague-Dawley rats were exposed to either HI right-sided brain injury or no HI injury. The HI rats were either untreated (HI + Diluent), single stem cell-treated (HI + MSCs\u00d71), or double stem cell-treated (HI + MSCs\u00d72). Control rats that were matched-for-weight and litter had no HI injury and were treated with diluent (Uninjured + Diluent). Treatment with AD-MSCs or diluent occurred either 7 days, or 7 and 9 days, after HI. There was a significant increase in the absolute number of striatal dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32)-positive MSNs in the double stem cell-treated (HI + MSCs\u00d72) group and the normal control group compared to the HI + Diluent group at PN21. We therefore investigated two potential mechanisms for this effect of double-treatment with AD-MSCs. Specifically, did AD-MSCs: (i) increase the proliferation of cells within the dlSVZ, and (ii) decrease the microglial response in the dlSVZ and striatum? It was found that a primary repair mechanism triggered by double treatment with AD-MSCs involved significantly decreased striatal inflammation. The results may lead to the development of clinically effective and less invasive stem cell therapies for neonatal HI brain injury.<\/jats:p>","DOI":"10.3390\/ijms22157862","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T10:31:44Z","timestamp":1627036304000},"page":"7862","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Delayed Double Treatment with Adult-Sourced Adipose-Derived Mesenchymal Stem Cells Increases Striatal Medium-Spiny Neuronal Number, Decreases Striatal Microglial Number, and Has No Subventricular Proliferative Effect, after Acute Neonatal Hypoxia-Ischemia in Male Rats"],"prefix":"10.3390","volume":"22","author":[{"given":"Haylee K.","family":"Basham","sequence":"first","affiliation":[{"name":"Department of Anatomy, School of Biomedical Sciences, and the Brain Health Research Centre, University of Otago, P.O. Box 913, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin E.","family":"Aghoghovwia","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Biomedical Sciences, and the Brain Health Research Centre, University of Otago, P.O. Box 913, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Papaioannou","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Biomedical Sciences, and the Brain Health Research Centre, University of Otago, P.O. Box 913, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5010-8971","authenticated-orcid":false,"given":"Steve","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Biomedical Sciences, and the Brain Health Research Centre, University of Otago, P.O. Box 913, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0212-4456","authenticated-orcid":false,"given":"Dorothy E.","family":"Oorschot","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Biomedical Sciences, and the Brain Health Research Centre, University of Otago, P.O. Box 913, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"F346","DOI":"10.1136\/archdischild-2015-309639","article-title":"Management and investigation of neonatal encephalopathy: 2017 update","volume":"102","author":"Martinello","year":"2017","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.baga.2012.11.001","article-title":"The percentage of interneurons in the dorsal striatum of the rat, cat, monkey and human: A critique of the evidence","volume":"3","author":"Oorschot","year":"2013","journal-title":"Basal Ganglia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/ana.410090206","article-title":"The influence of immaturity on hypoxic-ischemic brain damage in the rat","volume":"9","author":"Rice","year":"1981","journal-title":"Ann. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/0887-8994(91)90060-X","article-title":"Current concepts of hypoxic-ischemic cerebral injury in the term newborn","volume":"7","author":"Hill","year":"1991","journal-title":"Pediatrics Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1203\/00006450-199811000-00017","article-title":"Post-injury magnesium sulfate treatment is not markedly neuroprotective for striatal medium-spiny neurons following perinatal hypoxia\/ischemia in the rat","volume":"44","author":"Galvin","year":"1998","journal-title":"Pediatric Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.mcn.2015.03.019","article-title":"Delayed post-treatment with bone marrow-derived mesenchymal stem cells is neurorestorative of striatal medium-spiny projection neurons and improves motor function after neonatal rat hypoxia\u2013ischemia","volume":"68","author":"Cameron","year":"2015","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1542\/peds.102.5.1098","article-title":"Neuroprotection With Prolonged Head Cooling Started Before Postischemic Seizures in Fetal Sheep","volume":"102","author":"Gunn","year":"1998","journal-title":"Pediatrics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1365-2184.2008.00486.x","article-title":"Stem cells and neurological diseases","volume":"41","author":"Hess","year":"2007","journal-title":"Cell Prolif."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/j.1750-3639.2008.00146.x","article-title":"Neonatal Rat Hypoxia-Ischemia: Long-Term Rescue of Striatal Neurons and Motor Skills by Combined Antioxidant-Hypothermia Treatment","volume":"18","author":"Hobbs","year":"2008","journal-title":"Brain Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1161\/STROKEAHA.107.499822","article-title":"Xenon and hypothermia combine additively, offering long-term functional and histopathologic neuroprotection after neonatal hypoxia\/ischemia","volume":"39","author":"Hobbs","year":"2008","journal-title":"Stroke"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.bbi.2009.10.017","article-title":"Mesenchymal stem cell treatment after neonatal hypoxic-ischemic brain injury improves behavioral outcome and induces neuronal and oligodendrocyte regeneration","volume":"24","author":"Kavelaars","year":"2010","journal-title":"Brain Behav. Immunity"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9603","DOI":"10.1523\/JNEUROSCI.1835-10.2010","article-title":"Repeated mesenchymal stem cell treatment after neonatal hypoxia\u2013ischemia has distinct effects on formation and maturation of new neurons and oligodendrocytes leading to restoration of damage, corticospinal motor tract activity, and sensorimotor function","volume":"30","author":"Kavelaars","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ophelders, D.R.M.G., Gussenhoven, R., Klein, L., Jellema, R.K., Westerlaken, R.J., H\u00fctten, M.C., Vermeulen, J., Wassink, G., Gunn, A.J., and Wolfs, T.G. (2020). Preterm brain injury, antenatal triggers, and therapeutics: Timing is key. Cells, 9.","DOI":"10.3390\/cells9081871"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Archambault, J., Moreira, A., McDaniel, D., Winter, L., Sun, L., and Hornsby, P. (2017). Therapeutic potential of mesenchymal stromal cells for hypoxic ischemic encephalopathy: A systematic review and meta-analysis of preclinical studies. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189895"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1002\/sctm.19-0044","article-title":"Challenges in Clinical Development of Mesenchymal Stromal\/Stem Cells: Concise Review","volume":"8","author":"Mastrolia","year":"2019","journal-title":"STEM CELLS Transl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"675","DOI":"10.3109\/14653249.2010.549122","article-title":"Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy","volume":"13","author":"Ikegame","year":"2011","journal-title":"Cytotherapy"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.1089\/scd.2011.0722","article-title":"Same or Not the Same? Comparison of Adipose Tissue-Derived Versus Bone Marrow-Derived Mesenchymal Stem and Stromal Cells","volume":"21","author":"Strioga","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_18","first-page":"381","article-title":"Osteogenesis in transplants of bone marrow cells","volume":"16","author":"Friedenstein","year":"1966","journal-title":"J. Embryol. Exp. Morphol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage Potential of Adult Human Mesenchymal Stem Cells","volume":"284","author":"Pittenger","year":"1999","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"496218","DOI":"10.1155\/2013\/496218","article-title":"Therapeutic Potential of Mesenchymal Stem Cells in Regenerative Medicine","volume":"2013","author":"Patel","year":"2013","journal-title":"Stem Cells Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13287-015-0271-2","article-title":"Biodistribution, migration and homing of systemically applied mesenchymal stem\/stromal cells","volume":"7","author":"Leibacher","year":"2016","journal-title":"Stem Cell Res. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.expneurol.2014.06.009","article-title":"Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury","volume":"261","author":"Donega","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/jnr.10691","article-title":"Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat","volume":"73","author":"Chen","year":"2003","journal-title":"J. Neurosci. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/glia.20126","article-title":"Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells","volume":"49","author":"Li","year":"2005","journal-title":"Glia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.neuroscience.2006.04.054","article-title":"Bone marrow stromal cells upregulate expression of bone morphogenetic proteins 2 and 4, gap junction protein connexin-43 and synaptophysin after stroke in rats","volume":"141","author":"Zhang","year":"2006","journal-title":"Neuroscience"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"387","DOI":"10.3858\/emm.2008.40.4.387","article-title":"Mesenchymal stem cells promote proliferation of endogenous neural stem cells and survival of newborn cells in a rat stroke model","volume":"40","author":"Yoo","year":"2008","journal-title":"Exp. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.bbi.2011.03.021","article-title":"Mesenchymal stem cell transplantation changes the gene expression profile of the neonatal ischemic brain","volume":"25","author":"Kavelaars","year":"2011","journal-title":"Brain Behav. Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/pr.2011.64","article-title":"Mesenchymal stem cells as a treatment for neonatal ischemic brain damage","volume":"71","author":"Kavelaars","year":"2012","journal-title":"Pediatr. Res."},{"key":"ref_29","first-page":"419","article-title":"Nasal administration of stem cells: A promising novel route to treat neonatal ischemic brain damage","volume":"68","author":"Kavelaars","year":"2010","journal-title":"Pediatric Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bruschettini, M., Romantsik, O., Moreira, A., Ley, D., and Th\u00e9baud, B. (2018). Stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants. Cochrane Database Syst. Rev., 8.","DOI":"10.1002\/14651858.CD013202"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"864","DOI":"10.3109\/14653240903180084","article-title":"Labeling and tracking of mesenchymal stromal cells with EdU","volume":"11","author":"Lin","year":"2009","journal-title":"Cytotherapy"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1203\/PDR.0b013e3181bf594b","article-title":"Mesenchymal Stem-Cell Transplantation for Hypoxic-Ischemic Brain Injury in Neonatal Rat Model","volume":"67","author":"Lee","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/1479-5876-8-63","article-title":"Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats","volume":"8","author":"Leu","year":"2010","journal-title":"J. Transl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/scrt524","article-title":"Mesenchymal properties of SJL mice-stem cells and their efficacy as autologous therapy in a relapsing\u2013remitting multiple sclerosis model","volume":"5","author":"Guerrero","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1203\/PDR.0b013e318157d1fe","article-title":"Effect of hypothermic post-treatment on hypoxic-ischemic striatal injury, and normal striatal development, in neonatal rats: A stereological study","volume":"62","author":"Covey","year":"2007","journal-title":"Pediatric Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4359","DOI":"10.1523\/JNEUROSCI.1898-05.2006","article-title":"Neural Stem\/Progenitor Cells Participate in the Regenerative Response to Perinatal Hypoxia\/Ischemia","volume":"26","author":"Felling","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.neuroscience.2005.12.059","article-title":"Hypoxia\/ischemia expands the regenerative capacity of progenitors in the perinatal subventricular zone","volume":"139","author":"Yang","year":"2006","journal-title":"Neuroscience"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/ana.21068","article-title":"Sustained neocortical neurogenesis after neonatal hypoxic\/ischemic injury","volume":"61","author":"Yang","year":"2007","journal-title":"Ann. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"835","DOI":"10.3171\/2010.2.JNS09989","article-title":"Induction of striatal neurogenesis and generation of region-specific functional mature neurons after ischemia by growth factors","volume":"113","author":"Yoshikawa","year":"2010","journal-title":"J. Neurosurg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1203\/01.PDR.0000179381.86809.02","article-title":"Hypoxic-ischemic injury stimulates subventricular zone proliferation and neurogenesis in the neonatal rat","volume":"58","author":"Ong","year":"2005","journal-title":"Pediatric Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1159\/000105474","article-title":"Perinatal hypoxic\/ischemic brain injury induces persistent production of striatal neurons from subventricular zone progenitors","volume":"29","author":"Yang","year":"2007","journal-title":"Dev. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0165-3806(94)00177-2","article-title":"Microglia activation after neonatal hypoxia-ischemia","volume":"84","author":"McRae","year":"1995","journal-title":"Dev. Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1203\/00006450-199904010-00008","article-title":"Chemokine and inflammatory cell response to hypoxia-ischemia in immature rats","volume":"45","author":"Bona","year":"1999","journal-title":"Pediatric Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0896-6273(93)90281-U","article-title":"Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone","volume":"11","author":"Luskin","year":"1993","journal-title":"Neuron"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.neuroscience.2004.04.061","article-title":"Neurogenesis in the striatum of the quinolinic acid lesion model of Huntington\u2019s disease","volume":"127","author":"Tattersfield","year":"2004","journal-title":"Neuroscience"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.baga.2013.04.001","article-title":"Synaptic connectivity between rat striatal spiny projection neurons in vivo: Unexpected multiple somatic innervation in the context of overall sparse proximal connectivity","volume":"3","author":"Oorschot","year":"2013","journal-title":"Basal Ganglia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/S0006-8993(98)00724-0","article-title":"Quantitative immunocytochemistry of DARPP-32-expressing neurons in the rat caudatoputamen","volume":"808","author":"Ouimet","year":"1998","journal-title":"Brain Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1365-2818.1986.tb02764.x","article-title":"Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones, in memory of William R. Thompson","volume":"143","author":"Gundersen","year":"1986","journal-title":"J. Microsc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/(SICI)1096-9861(19960318)366:4<580::AID-CNE3>3.0.CO;2-0","article-title":"Total number of neurons in the neostriatal, pallidal, subthalamic, and substantia nigral nuclei of the rat basal ganglia: A stereological study using the cavalieri and optical disector methods","volume":"366","author":"Oorschot","year":"1996","journal-title":"J. Comp. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/joa.12495","article-title":"Absolute number of parvicellular and magnocellular neurons in the red nucleus of the rat midbrain: A stereological study","volume":"229","author":"Aghoghovwia","year":"2016","journal-title":"J. Anat."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1002\/ar.24196","article-title":"Long-Term Fine Motor Capability on the Staircase Test Correlates with the Absolute Number, but Not the Density, of DARPP-Positive Neurons in the Caudate-Putamen","volume":"302","author":"Aghoghovwia","year":"2019","journal-title":"Anat. Rec. Adv. Integr. Anat. Evol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0165-0270(80)90021-7","article-title":"AChE-stained horizontal sections of the rat brain in stereotaxic coordinates","volume":"3","author":"Paxinos","year":"1980","journal-title":"J. Neurosci. Methods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1365-2818.1977.tb00062.x","article-title":"Notes on the estimation of the numerical density of arbitrary profiles: The edge effect","volume":"111","author":"Gundersen","year":"1977","journal-title":"J. Microsc."},{"key":"ref_54","first-page":"93","article-title":"Effects of undernutrition on brain morphology: A critical review of methods and results","volume":"Volume 2","author":"Jones","year":"1984","journal-title":"Current Topics in Research on Synapses"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0301-0082(94)90040-X","article-title":"Are you using neuronal densities, synaptic densities or neurochemical densities as your definitive data? there is a better way to go","volume":"44","author":"Oorschot","year":"1994","journal-title":"Prog. Neurobiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5566\/ias.v30.p1-9","article-title":"Indirect measures of neuroprotection are parameters to avoid: Examples from research on neonatal rat hypoxia-ischemia","volume":"30","author":"Oorschot","year":"2011","journal-title":"Image Anal. Ster."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5655","DOI":"10.1242\/jcs.01488","article-title":"In vivo contribution of murine mesenchymal stem cells into multiple cell-types under minimal damage conditions","volume":"117","author":"Afonso","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Zhao, L.-R., and Zhang, J.H. (2015). Cord blood as a treatment for stroke. Cellular Therapy for Stroke and CNS Injuries, Springer.","DOI":"10.1007\/978-3-319-11481-1"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"a025874","DOI":"10.1101\/cshperspect.a025874","article-title":"The Role of the Microenvironmental Niche in Declining Stem-Cell Functions Associated with Biological Aging","volume":"5","author":"Decarolis","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"484","DOI":"10.3346\/jkms.2008.23.3.484","article-title":"Erythropoietin Attenuates Brain Injury, Subventricular Zone Expansion, and Sensorimotor Deficits in Hypoxic-Ischemic Neonatal Rats","volume":"23","author":"Kim","year":"2008","journal-title":"J. Korean Med. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3727\/215517913X658936","article-title":"Transplantation of Human Adipose Tissue-Derived Mesenchymal Stem Cells Restores the Neurobehavioral Disorders of Rats with Neonatal Hypoxic-Ischemic Encephalopathy","volume":"5","author":"Park","year":"2013","journal-title":"Cell Med."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Donega, V., Nijboer, C.H., Braccioli, L., Slaper-Cortenbach, I., Kavelaars, A., Van Bel, F., and Heijnen, C.J. (2014). Intranasal Administration of Human MSC for Ischemic Brain Injury in the Mouse: In Vitro and In Vivo Neuroregenerative Functions. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112339"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1097\/nen.0b013e3181256b32","article-title":"Distinct types of microglia activation in white and grey matter of rat lumbosacral cord after mid-thoracic spinal transection","volume":"66","author":"McKay","year":"2007","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/j.1365-2818.1990.tb02967.x","article-title":"The total number of neurons in the human neocortex unbiasedly estimated using optical disectors","volume":"157","author":"Braendgaard","year":"1990","journal-title":"J. Microsc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.neuroscience.2005.06.086","article-title":"Estimators of the precision of stereological estimates: An example based on the CA1 pyramidal cell layer of rats","volume":"136","author":"Slomianka","year":"2005","journal-title":"Neuroscience"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1016\/S0140-6736(08)60690-X","article-title":"Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: A phase II study","volume":"371","author":"Frassoni","year":"2008","journal-title":"Lancet"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ymeth.2008.03.006","article-title":"Adipose-derived stem cells: Isolation, expansion and differentiation","volume":"45","author":"Bunnell","year":"2008","journal-title":"Methods"},{"key":"ref_69","first-page":"625","article-title":"The Endogenous Regenerative Capacity of the Damaged Newborn Brain: Boosting Neurogenesis with Mesenchymal Stem Cell Treatment","volume":"33","author":"Donega","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1089\/107632703768247377","article-title":"In Vitro Chondrogenesis of Bone Marrow-Derived Mesenchymal Stem Cells in a Photopolymerizing Hydrogel","volume":"9","author":"Williams","year":"2003","journal-title":"Tissue Eng."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"345806","DOI":"10.4061\/2010\/345806","article-title":"Fate of Bone Marrow-Derived Stromal Cells after Intraperitoneal Infusion or Implantation into Femoral Bone Defects in the Host Animal","volume":"1","author":"Wilson","year":"2010","journal-title":"J. Tissue Eng."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.neulet.2008.10.040","article-title":"Human mesenchymal stem cells abrogate experimental allergic encephalomyelitis after intraperitoneal injection, and with sparse CNS infiltration","volume":"448","author":"Gordon","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"624640","DOI":"10.1155\/2014\/624640","article-title":"Intraperitoneal Infusion of Mesenchymal Stem\/Stromal Cells Prevents Experimental Autoimmune Uveitis in Mice","volume":"2014","author":"Oh","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1161\/01.STR.0000141680.49960.d7","article-title":"Central Nervous System Entry of Peripherally Injected Umbilical Cord Blood Cells Is Not Required for Neuroprotection in Stroke","volume":"35","author":"Borlongan","year":"2004","journal-title":"Stroke"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/cne.21819","article-title":"Neonatal hypoxic\/ischemic brain injury induces production of calretinin-expressing interneurons in the striatum","volume":"511","author":"Yang","year":"2008","journal-title":"J. Comp. Neurol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1161\/01.STR.0000190020.30282.cc","article-title":"Neurogenesis in Rats After Focal Cerebral Ischemia is Enhanced by Indomethacin","volume":"36","author":"Hoehn","year":"2005","journal-title":"Stroke"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/scrt159","article-title":"Effects of intravenous administration of allogenic bone marrow- and adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke","volume":"4","author":"Fuentes","year":"2013","journal-title":"Stem Cell Res. 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