Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
2010-7-15
pubmed:abstractText
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 vitro culture with HI brain extracts obtained at day 10 from MSC-3- or vehicle-treated animals by pathway-focused PCR array analysis revealed that 29 genes encoding secreted factors were indeed differentially regulated. We propose that the function of MSCs is dictated by adaptive specific signals provided by the damaged and regenerating brain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9603-11
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
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.
pubmed:affiliation
Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't