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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

Active macrophages in the periventricular brain tissue after severe IVH in newborn rats.A, Representative immunofluorescence photomicrographs of the periventricular area with staining for ED-1 (green) and DAPI (blue) (original magnification; x400, scale bars; 20 μm). B, Average number of ED-1 positive cells in the periventricular area. 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 UCB-MSCs; IMV+man, IVH with intravenous transplantation of human UCB-MSCs+mannitol; IMC, IVH with intracerebroventricular transplantation of human UCB-MSC. * P <0.05 vs. NC, # P <0.05 vs. IC, †P <0.05 vs. IC+man.
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pone.0132919.g006: Active macrophages in the periventricular brain tissue after severe IVH in newborn rats.A, Representative immunofluorescence photomicrographs of the periventricular area with staining for ED-1 (green) and DAPI (blue) (original magnification; x400, scale bars; 20 μm). B, Average number of ED-1 positive cells in the periventricular area. 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 UCB-MSCs; IMV+man, IVH with intravenous transplantation of human UCB-MSCs+mannitol; IMC, IVH with intracerebroventricular transplantation of human UCB-MSC. * P <0.05 vs. NC, # P <0.05 vs. IC, †P <0.05 vs. IC+man.

Mentions: To determine whether transplanted MSCs attenuated brain inflammation induced by severe IVH, we analyzed levels of inflammatory cytokines including IL-1α, IL-1β, IL-6, and TNF-α in periventricular brain tissue homogenates and the number of ED-1 positive cells in brain coronal sections at P32. Inflammatory cytokine and ED-1 positive cell levels in the periventricular brain tissue were significantly higher in the IC group than in the NC group. These increased inflammatory responses were significantly attenuated in the IMC, IMV, and IMV+man groups but not in the IC+man group (Figs 5 and 6).


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)

Active macrophages in the periventricular brain tissue after severe IVH in newborn rats.A, Representative immunofluorescence photomicrographs of the periventricular area with staining for ED-1 (green) and DAPI (blue) (original magnification; x400, scale bars; 20 μm). B, Average number of ED-1 positive cells in the periventricular area. 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 UCB-MSCs; IMV+man, IVH with intravenous transplantation of human UCB-MSCs+mannitol; IMC, IVH with intracerebroventricular transplantation of human UCB-MSC. * P <0.05 vs. NC, # P <0.05 vs. IC, †P <0.05 vs. IC+man.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132919.g006: Active macrophages in the periventricular brain tissue after severe IVH in newborn rats.A, Representative immunofluorescence photomicrographs of the periventricular area with staining for ED-1 (green) and DAPI (blue) (original magnification; x400, scale bars; 20 μm). B, Average number of ED-1 positive cells in the periventricular area. 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 UCB-MSCs; IMV+man, IVH with intravenous transplantation of human UCB-MSCs+mannitol; IMC, IVH with intracerebroventricular transplantation of human UCB-MSC. * P <0.05 vs. NC, # P <0.05 vs. IC, †P <0.05 vs. IC+man.
Mentions: To determine whether transplanted MSCs attenuated brain inflammation induced by severe IVH, we analyzed levels of inflammatory cytokines including IL-1α, IL-1β, IL-6, and TNF-α in periventricular brain tissue homogenates and the number of ED-1 positive cells in brain coronal sections at P32. Inflammatory cytokine and ED-1 positive cell levels in the periventricular brain tissue were significantly higher in the IC group than in the NC group. These increased inflammatory responses were significantly attenuated in the IMC, IMV, and IMV+man groups but not in the IC+man group (Figs 5 and 6).

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