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Engraftment of human mesenchymal stem cells in a rat photothrombotic cerebral infarction model : comparison of intra-arterial and intravenous infusion using MRI and histological analysis.

Byun JS, Kwak BK, Kim JK, Jung J, Ha BC, Park S - J Korean Neurosurg Soc (2013)

Bottom Line: In IA group, dark signals in peri-lesional zone were more prominent compared with IV group.SWI showed largest dark signal followed by T2(*)WI and T2WI in both IA and IV groups.In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Chung-Ang University College of Medicine, Seoul, Korea.

ABSTRACT

Objective: This study aimed to evaluate the hypotheses that administration routes [intra-arterial (IA) vs. intravenous (IV)] affect the early stage migration of transplanted human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in acute brain infarction.

Methods: Male Sprague-Dawley rats (n=40) were subjected to photothrombotic infarction. Three days after photothrombotic infarction, rats were randomly allocated to one of four experimental groups [IA group : n=12, IV group : n=12, superparamagnetic iron oxide (SPIO) group : n=8, control group : n=8]. All groups were subdivided into 1, 6, 24, and 48 hours groups according to time point of sacrifice. Magnetic resonance imaging (MRI) consisting of T2 weighted image (T2WI), T2(*) weighted image (T2(*)WI), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining.

Results: Grafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. SWI showed largest dark signal followed by T2(*)WI and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups.

Conclusion: In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain.

No MeSH data available.


Related in: MedlinePlus

MRI of rat brain (IA 48 hr), SPIO-labeled hBM-MSCs directly grafted into a rat brain, and Prussian blue-stained cells and antimitochondrial-Prussian blue stained cells in a rat brain. A : Implanted cells are visualized as low signal intensity on SWI of MRI. B : Hypointense areas [square in (A)] represent massive invasions by Prussian blue stained cells (original magnification ×200, ×400). C : Graph showing the mean (±SE) number of engrafted cells in brain after either selective IA or IV transplantation (*p<0.05). D : Among these cells antimitochondrial-Prussian blue stained cells are noted (arrows, original magnification ×400). IA : intra-arterial, IV : intravenous, SPIO : superparamagnetic iron oxide, SWI : susceptibility weighted image, hBM-MSCs : human bone marrow-derived mesenchymal stem cells.
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Figure 6: MRI of rat brain (IA 48 hr), SPIO-labeled hBM-MSCs directly grafted into a rat brain, and Prussian blue-stained cells and antimitochondrial-Prussian blue stained cells in a rat brain. A : Implanted cells are visualized as low signal intensity on SWI of MRI. B : Hypointense areas [square in (A)] represent massive invasions by Prussian blue stained cells (original magnification ×200, ×400). C : Graph showing the mean (±SE) number of engrafted cells in brain after either selective IA or IV transplantation (*p<0.05). D : Among these cells antimitochondrial-Prussian blue stained cells are noted (arrows, original magnification ×400). IA : intra-arterial, IV : intravenous, SPIO : superparamagnetic iron oxide, SWI : susceptibility weighted image, hBM-MSCs : human bone marrow-derived mesenchymal stem cells.

Mentions: Intravascular transplantation of SPIO-labeled hBM-MSCs in this photothrombotic model resulted in cerebral engraftment detected by Prussian blue staining. The distribution of transplanted cells varied in different cerebral regions. The highest cell density was detected in the peri-lesional zone, although some cells were detected at distances from the infarction. The dark signal intensity regions observed on MRI were found to correspond to grafted regions as determined by Prussian blue staining (Fig. 6A, B). Counting of SPIO-labeled hBM-MSCs showed that significantly greater numbers of cells were engrafted at 48 hours in groups treated by IA administration (p<0.05) (Fig. 6C). At 48 hours after IA injection, the mean cell number observed within the cerebrum was 52.8 as compared to 25.4 after IV. At 1, 6, and 24 hours, only rare transplanted cells were observed in either the IA or IV groups. Mean cell numbers of 5.8, 7.2, and 8.3, respectively, were detected within the brain at these times after IA injection vs. 1.0, 1.8, and 3.3 after IV, but these differences between IA and IV groups were not significant. In both groups, cell engraftments at 48 hours was significantly superior than those at one hour after cell infusion (p<0.05). Engrafted cells were not detected in SPIO and control groups.


Engraftment of human mesenchymal stem cells in a rat photothrombotic cerebral infarction model : comparison of intra-arterial and intravenous infusion using MRI and histological analysis.

Byun JS, Kwak BK, Kim JK, Jung J, Ha BC, Park S - J Korean Neurosurg Soc (2013)

MRI of rat brain (IA 48 hr), SPIO-labeled hBM-MSCs directly grafted into a rat brain, and Prussian blue-stained cells and antimitochondrial-Prussian blue stained cells in a rat brain. A : Implanted cells are visualized as low signal intensity on SWI of MRI. B : Hypointense areas [square in (A)] represent massive invasions by Prussian blue stained cells (original magnification ×200, ×400). C : Graph showing the mean (±SE) number of engrafted cells in brain after either selective IA or IV transplantation (*p<0.05). D : Among these cells antimitochondrial-Prussian blue stained cells are noted (arrows, original magnification ×400). IA : intra-arterial, IV : intravenous, SPIO : superparamagnetic iron oxide, SWI : susceptibility weighted image, hBM-MSCs : human bone marrow-derived mesenchymal stem cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921273&req=5

Figure 6: MRI of rat brain (IA 48 hr), SPIO-labeled hBM-MSCs directly grafted into a rat brain, and Prussian blue-stained cells and antimitochondrial-Prussian blue stained cells in a rat brain. A : Implanted cells are visualized as low signal intensity on SWI of MRI. B : Hypointense areas [square in (A)] represent massive invasions by Prussian blue stained cells (original magnification ×200, ×400). C : Graph showing the mean (±SE) number of engrafted cells in brain after either selective IA or IV transplantation (*p<0.05). D : Among these cells antimitochondrial-Prussian blue stained cells are noted (arrows, original magnification ×400). IA : intra-arterial, IV : intravenous, SPIO : superparamagnetic iron oxide, SWI : susceptibility weighted image, hBM-MSCs : human bone marrow-derived mesenchymal stem cells.
Mentions: Intravascular transplantation of SPIO-labeled hBM-MSCs in this photothrombotic model resulted in cerebral engraftment detected by Prussian blue staining. The distribution of transplanted cells varied in different cerebral regions. The highest cell density was detected in the peri-lesional zone, although some cells were detected at distances from the infarction. The dark signal intensity regions observed on MRI were found to correspond to grafted regions as determined by Prussian blue staining (Fig. 6A, B). Counting of SPIO-labeled hBM-MSCs showed that significantly greater numbers of cells were engrafted at 48 hours in groups treated by IA administration (p<0.05) (Fig. 6C). At 48 hours after IA injection, the mean cell number observed within the cerebrum was 52.8 as compared to 25.4 after IV. At 1, 6, and 24 hours, only rare transplanted cells were observed in either the IA or IV groups. Mean cell numbers of 5.8, 7.2, and 8.3, respectively, were detected within the brain at these times after IA injection vs. 1.0, 1.8, and 3.3 after IV, but these differences between IA and IV groups were not significant. In both groups, cell engraftments at 48 hours was significantly superior than those at one hour after cell infusion (p<0.05). Engrafted cells were not detected in SPIO and control groups.

Bottom Line: In IA group, dark signals in peri-lesional zone were more prominent compared with IV group.SWI showed largest dark signal followed by T2(*)WI and T2WI in both IA and IV groups.In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Chung-Ang University College of Medicine, Seoul, Korea.

ABSTRACT

Objective: This study aimed to evaluate the hypotheses that administration routes [intra-arterial (IA) vs. intravenous (IV)] affect the early stage migration of transplanted human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in acute brain infarction.

Methods: Male Sprague-Dawley rats (n=40) were subjected to photothrombotic infarction. Three days after photothrombotic infarction, rats were randomly allocated to one of four experimental groups [IA group : n=12, IV group : n=12, superparamagnetic iron oxide (SPIO) group : n=8, control group : n=8]. All groups were subdivided into 1, 6, 24, and 48 hours groups according to time point of sacrifice. Magnetic resonance imaging (MRI) consisting of T2 weighted image (T2WI), T2(*) weighted image (T2(*)WI), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining.

Results: Grafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. SWI showed largest dark signal followed by T2(*)WI and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups.

Conclusion: In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain.

No MeSH data available.


Related in: MedlinePlus