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Optimal Route for Mesenchymal Stem Cells Transplantation after Severe Intraventricular Hemorrhage in Newborn Rats.

Ahn SY, Chang YS, Sung DK, Sung SI, Yoo HS, Im GH, Choi SJ, Park WS - PLoS ONE (2015)

Bottom Line: At P32, brain tissue samples were obtained for biochemical and histological analyses.Although more MSCs localized to the brain after IC than after IV delivery, both methods were equally effective in preventing PHH; attenuating impaired rotarod test; increasing the number of TUNEL-positive cells, inflammatory cytokines, and astrogliosis; and reducing corpus callosal thickness and myelin basic protein expression after severe IVH regardless of mannitol co-infusion.These findings suggest that the less invasive IV route might be a good alternative for clinically unstable, very preterm infants that cannot tolerate a more invasive IC delivery of MSCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT
Recently, we showed that intracerebroventricular (IC) transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) significantly attenuates posthemorrhagic hydrocephalus (PHH) and brain damage after severe IVH in newborn rats. This study was performed to determine the optimal route for transplanting MSCs for severe IVH by comparing IC transplantation, intravenous (IV) transplantation, and IV transplantation plus mannitol infusion. Severe IVH was induced by injecting 100 uL of blood into each ventricle of Sprague-Dawley rats on postnatal day 4 (P4). After confirming severe IVH with brain magnetic resonance imaging (MRI) at P5, human UCB-derived MSCs were transplanted at P6 by an IC route (1×105), an IV route (5×105), or an IV route with mannitol infused. Follow-up brain MRIs and rotarod tests were performed. At P32, brain tissue samples were obtained for biochemical and histological analyses. Although more MSCs localized to the brain after IC than after IV delivery, both methods were equally effective in preventing PHH; attenuating impaired rotarod test; increasing the number of TUNEL-positive cells, inflammatory cytokines, and astrogliosis; and reducing corpus callosal thickness and myelin basic protein expression after severe IVH regardless of mannitol co-infusion. Despite the superior delivery efficacy with IC than with the IV route, both IC and IV transplantation of MSCs had equal therapeutic efficacy in protecting against severe IVH. These findings suggest that the less invasive IV route might be a good alternative for clinically unstable, very preterm infants that cannot tolerate a more invasive IC delivery of MSCs.

No MeSH data available.


Related in: MedlinePlus

Vetricular dilatation and its progression after severe intraventricular hemorrhage (IVH).A, Representative serial brain MRIs from each group 1, 7, and 28 days after inducing IVH (P5/P11/P32). B, The ventricle to whole brain volume ratio as measured by MRI. Data are expressed as mean ± SEM. NC, normal control rats; IC, IVH control rats; IC+man, IVH control rats+mannitol; IMV, IVH with intravenous transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs); IMV+man, IVH with intravenous transplantation of human UCB-MSCs+mannitol; IMC, IVH with intracerebroventricular transplantation of human UCB-MSCs. * P <0.05 vs. NC, # P <0.05 vs. IC, †P <0.05 vs. IC+man
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pone.0132919.g001: Vetricular dilatation and its progression after severe intraventricular hemorrhage (IVH).A, Representative serial brain MRIs from each group 1, 7, and 28 days after inducing IVH (P5/P11/P32). B, The ventricle to whole brain volume ratio as measured by MRI. Data are expressed as mean ± SEM. NC, normal control rats; IC, IVH control rats; IC+man, IVH control rats+mannitol; IMV, IVH with intravenous transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs); IMV+man, IVH with intravenous transplantation of human UCB-MSCs+mannitol; IMC, IVH with intracerebroventricular transplantation of human UCB-MSCs. * P <0.05 vs. NC, # P <0.05 vs. IC, †P <0.05 vs. IC+man

Mentions: Fig 1A displays serial brain MRIs from each study group performed at 1, 7, and 28 days after inducing IVH (P5, P11, and P32, respectively). The ventricular dilatation severity, presented as a ratio of the ventricle to whole brain volume, 1 day after inducing IVH (P5) was significantly higher in the IVH induced groups than in the NC group but did not differ significantly among the experimental groups (15.5±0.8%, 15.8±1.0%, 13.8±0.9%, 13.9±0.7%, 13.1±0.6%, and 14.1±0.3% in the IC, IC+man, IMV, IMV+man, and IMC groups, respectively) (Fig 1B). On follow-up MRIs done at P11 and P32 after infusing vehicle or MSCs with and without mannitol at P6, the IC group had active progression of ventriculomegaly (30.3±6.1% at P32), which was significantly attenuated in the IMV, IMV+ man, and IMC groups (12.3±3.8%, 13.2±3.0%, and 18.7±2.6%, respectively, at P32) but not in the IC+man group (25.6±3.7%). These results suggest that both IV and IC MSC transplantation were equally effective in attenuating PHH after severe IVH, but mannitol neither improved PHH nor enhanced protection by IV MSCs.


Optimal Route for Mesenchymal Stem Cells Transplantation after Severe Intraventricular Hemorrhage in Newborn Rats.

Ahn SY, Chang YS, Sung DK, Sung SI, Yoo HS, Im GH, Choi SJ, Park WS - PLoS ONE (2015)

Vetricular dilatation and its progression after severe intraventricular hemorrhage (IVH).A, Representative serial brain MRIs from each group 1, 7, and 28 days after inducing IVH (P5/P11/P32). B, The ventricle to whole brain volume ratio as measured by MRI. Data are expressed as mean ± SEM. NC, normal control rats; IC, IVH control rats; IC+man, IVH control rats+mannitol; IMV, IVH with intravenous transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs); IMV+man, IVH with intravenous transplantation of human UCB-MSCs+mannitol; IMC, IVH with intracerebroventricular transplantation of human UCB-MSCs. * P <0.05 vs. NC, # P <0.05 vs. IC, †P <0.05 vs. IC+man
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4514759&req=5

pone.0132919.g001: Vetricular dilatation and its progression after severe intraventricular hemorrhage (IVH).A, Representative serial brain MRIs from each group 1, 7, and 28 days after inducing IVH (P5/P11/P32). B, The ventricle to whole brain volume ratio as measured by MRI. Data are expressed as mean ± SEM. NC, normal control rats; IC, IVH control rats; IC+man, IVH control rats+mannitol; IMV, IVH with intravenous transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs); IMV+man, IVH with intravenous transplantation of human UCB-MSCs+mannitol; IMC, IVH with intracerebroventricular transplantation of human UCB-MSCs. * P <0.05 vs. NC, # P <0.05 vs. IC, †P <0.05 vs. IC+man
Mentions: Fig 1A displays serial brain MRIs from each study group performed at 1, 7, and 28 days after inducing IVH (P5, P11, and P32, respectively). The ventricular dilatation severity, presented as a ratio of the ventricle to whole brain volume, 1 day after inducing IVH (P5) was significantly higher in the IVH induced groups than in the NC group but did not differ significantly among the experimental groups (15.5±0.8%, 15.8±1.0%, 13.8±0.9%, 13.9±0.7%, 13.1±0.6%, and 14.1±0.3% in the IC, IC+man, IMV, IMV+man, and IMC groups, respectively) (Fig 1B). On follow-up MRIs done at P11 and P32 after infusing vehicle or MSCs with and without mannitol at P6, the IC group had active progression of ventriculomegaly (30.3±6.1% at P32), which was significantly attenuated in the IMV, IMV+ man, and IMC groups (12.3±3.8%, 13.2±3.0%, and 18.7±2.6%, respectively, at P32) but not in the IC+man group (25.6±3.7%). These results suggest that both IV and IC MSC transplantation were equally effective in attenuating PHH after severe IVH, but mannitol neither improved PHH nor enhanced protection by IV MSCs.

Bottom Line: At P32, brain tissue samples were obtained for biochemical and histological analyses.Although more MSCs localized to the brain after IC than after IV delivery, both methods were equally effective in preventing PHH; attenuating impaired rotarod test; increasing the number of TUNEL-positive cells, inflammatory cytokines, and astrogliosis; and reducing corpus callosal thickness and myelin basic protein expression after severe IVH regardless of mannitol co-infusion.These findings suggest that the less invasive IV route might be a good alternative for clinically unstable, very preterm infants that cannot tolerate a more invasive IC delivery of MSCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT
Recently, we showed that intracerebroventricular (IC) transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) significantly attenuates posthemorrhagic hydrocephalus (PHH) and brain damage after severe IVH in newborn rats. This study was performed to determine the optimal route for transplanting MSCs for severe IVH by comparing IC transplantation, intravenous (IV) transplantation, and IV transplantation plus mannitol infusion. Severe IVH was induced by injecting 100 uL of blood into each ventricle of Sprague-Dawley rats on postnatal day 4 (P4). After confirming severe IVH with brain magnetic resonance imaging (MRI) at P5, human UCB-derived MSCs were transplanted at P6 by an IC route (1×105), an IV route (5×105), or an IV route with mannitol infused. Follow-up brain MRIs and rotarod tests were performed. At P32, brain tissue samples were obtained for biochemical and histological analyses. Although more MSCs localized to the brain after IC than after IV delivery, both methods were equally effective in preventing PHH; attenuating impaired rotarod test; increasing the number of TUNEL-positive cells, inflammatory cytokines, and astrogliosis; and reducing corpus callosal thickness and myelin basic protein expression after severe IVH regardless of mannitol co-infusion. Despite the superior delivery efficacy with IC than with the IV route, both IC and IV transplantation of MSCs had equal therapeutic efficacy in protecting against severe IVH. These findings suggest that the less invasive IV route might be a good alternative for clinically unstable, very preterm infants that cannot tolerate a more invasive IC delivery of MSCs.

No MeSH data available.


Related in: MedlinePlus