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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

Serial brain MRI after regions IA (A) and IV (B) administration after photothrombotic infarction of rat model. Acute infarction are located on the right side of the brain (the left side of the images). Dark signal intensity regions increased over time especially in peripheral portion of infarction. SWI shows largest dark signal intensity regions following T2*WI and T2WI (arrows). Linear parenchymal low-signal intensities suggestive of veins are noted in all groups on SWI (double arrows). In the IA group, dark signal intensity in peripheral portion of infarction are more prominent than incorresponding images from a the IV group. PTCI : photothrombotic cerebral infarction, IA : intra-arterial, IV : intravenous, T2*WI : T2* weighted image, T2WI : T2 weighted image, SWI : susceptibility weighted image, DWI : diffusion weighted image.
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Figure 4: Serial brain MRI after regions IA (A) and IV (B) administration after photothrombotic infarction of rat model. Acute infarction are located on the right side of the brain (the left side of the images). Dark signal intensity regions increased over time especially in peripheral portion of infarction. SWI shows largest dark signal intensity regions following T2*WI and T2WI (arrows). Linear parenchymal low-signal intensities suggestive of veins are noted in all groups on SWI (double arrows). In the IA group, dark signal intensity in peripheral portion of infarction are more prominent than incorresponding images from a the IV group. PTCI : photothrombotic cerebral infarction, IA : intra-arterial, IV : intravenous, T2*WI : T2* weighted image, T2WI : T2 weighted image, SWI : susceptibility weighted image, DWI : diffusion weighted image.

Mentions: On MRI, the brain infarction presented high signal intensity on T2WI. On T2WI, T2*WI, and SWI, grafted cells appeared as dark signal intensity at the ischemic boundary. In the IA group, dark signal intensity in the zone surrounding the infarction increased substantially over time. SWI showed largest dark signal intensity regions followed by T2*WI and T2WI in all groups. In the IV group, dark signal intensity were also observed in the peri-lesional zone but were less prominent than in corresponding images from the IA group. Distributions of dark signal intensities in peri-lesional zones were similar in both IA and IV groups (Fig. 4). Linear parenchymal low-signal intensities suggestive of veins were noted in all groups on SWI. On T2WI and DWI, a high signal intensity lesion was seen in deep gray matter of brain suggestive of acute infarction and probably caused by a cluster of cells. On SWI the pixel counts of dark signal intensity in the peri-lesional zone were significantly larger in groups that received IA administration (p<0.05). Mean dark signal intensity pixel numbers of 478.6±9.0, 570.4±22.2, 789.7±21.1, and 722.5±9.3 were detected in the brain at 1, 6, 24, and 48 hours, respectively, after IA injection vs. 205.3±20.7, 240.7±11.1, 374.2±28, and 380.8±38.5 after IV (Fig. 5).


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)

Serial brain MRI after regions IA (A) and IV (B) administration after photothrombotic infarction of rat model. Acute infarction are located on the right side of the brain (the left side of the images). Dark signal intensity regions increased over time especially in peripheral portion of infarction. SWI shows largest dark signal intensity regions following T2*WI and T2WI (arrows). Linear parenchymal low-signal intensities suggestive of veins are noted in all groups on SWI (double arrows). In the IA group, dark signal intensity in peripheral portion of infarction are more prominent than incorresponding images from a the IV group. PTCI : photothrombotic cerebral infarction, IA : intra-arterial, IV : intravenous, T2*WI : T2* weighted image, T2WI : T2 weighted image, SWI : susceptibility weighted image, DWI : diffusion weighted image.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Serial brain MRI after regions IA (A) and IV (B) administration after photothrombotic infarction of rat model. Acute infarction are located on the right side of the brain (the left side of the images). Dark signal intensity regions increased over time especially in peripheral portion of infarction. SWI shows largest dark signal intensity regions following T2*WI and T2WI (arrows). Linear parenchymal low-signal intensities suggestive of veins are noted in all groups on SWI (double arrows). In the IA group, dark signal intensity in peripheral portion of infarction are more prominent than incorresponding images from a the IV group. PTCI : photothrombotic cerebral infarction, IA : intra-arterial, IV : intravenous, T2*WI : T2* weighted image, T2WI : T2 weighted image, SWI : susceptibility weighted image, DWI : diffusion weighted image.
Mentions: On MRI, the brain infarction presented high signal intensity on T2WI. On T2WI, T2*WI, and SWI, grafted cells appeared as dark signal intensity at the ischemic boundary. In the IA group, dark signal intensity in the zone surrounding the infarction increased substantially over time. SWI showed largest dark signal intensity regions followed by T2*WI and T2WI in all groups. In the IV group, dark signal intensity were also observed in the peri-lesional zone but were less prominent than in corresponding images from the IA group. Distributions of dark signal intensities in peri-lesional zones were similar in both IA and IV groups (Fig. 4). Linear parenchymal low-signal intensities suggestive of veins were noted in all groups on SWI. On T2WI and DWI, a high signal intensity lesion was seen in deep gray matter of brain suggestive of acute infarction and probably caused by a cluster of cells. On SWI the pixel counts of dark signal intensity in the peri-lesional zone were significantly larger in groups that received IA administration (p<0.05). Mean dark signal intensity pixel numbers of 478.6±9.0, 570.4±22.2, 789.7±21.1, and 722.5±9.3 were detected in the brain at 1, 6, 24, and 48 hours, respectively, after IA injection vs. 205.3±20.7, 240.7±11.1, 374.2±28, and 380.8±38.5 after IV (Fig. 5).

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