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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

In vitro cellular MRI of PBS phantoms containing suspensions of different concentrations of SPIO labeled hBM-MSCs. A : T2 weighted image. B : T2* weighted image (GRE). C : Susceptibility weighted image. (a) 6.3×104 cells/mL, (b) 1.3×105 cells/mL, (c) 2.5×105 cells/mL, (d) 5.0×105 cells/mL, (e) unlabeled hMSC 5.0×105 cells/mL, (f) no cells (normal saline). PBS : phosphate-buffered saline, hBM-MSCs : human bone marrow-derived mesenchymal stem cells, SPIO : superparamagnetic iron oxide, hMSC : human mesenchymal stem cell.
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Figure 3: In vitro cellular MRI of PBS phantoms containing suspensions of different concentrations of SPIO labeled hBM-MSCs. A : T2 weighted image. B : T2* weighted image (GRE). C : Susceptibility weighted image. (a) 6.3×104 cells/mL, (b) 1.3×105 cells/mL, (c) 2.5×105 cells/mL, (d) 5.0×105 cells/mL, (e) unlabeled hMSC 5.0×105 cells/mL, (f) no cells (normal saline). PBS : phosphate-buffered saline, hBM-MSCs : human bone marrow-derived mesenchymal stem cells, SPIO : superparamagnetic iron oxide, hMSC : human mesenchymal stem cell.

Mentions: MRI obtained at 6.3×104, 1.3×105, 2.5×105 and 5.0×105, cells showed that ferumoxide-labeling caused signals to become dark in a dose-dependent manner. Among the pulse sequences, SWI showed the maximum susceptibility effect of SPIO followed by T2*WI and T2WI. No significant susceptibility effect was noted in unlabeled hBM-MSCs or normal saline on MRI (Fig. 3).


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)

In vitro cellular MRI of PBS phantoms containing suspensions of different concentrations of SPIO labeled hBM-MSCs. A : T2 weighted image. B : T2* weighted image (GRE). C : Susceptibility weighted image. (a) 6.3×104 cells/mL, (b) 1.3×105 cells/mL, (c) 2.5×105 cells/mL, (d) 5.0×105 cells/mL, (e) unlabeled hMSC 5.0×105 cells/mL, (f) no cells (normal saline). PBS : phosphate-buffered saline, hBM-MSCs : human bone marrow-derived mesenchymal stem cells, SPIO : superparamagnetic iron oxide, hMSC : human mesenchymal stem cell.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: In vitro cellular MRI of PBS phantoms containing suspensions of different concentrations of SPIO labeled hBM-MSCs. A : T2 weighted image. B : T2* weighted image (GRE). C : Susceptibility weighted image. (a) 6.3×104 cells/mL, (b) 1.3×105 cells/mL, (c) 2.5×105 cells/mL, (d) 5.0×105 cells/mL, (e) unlabeled hMSC 5.0×105 cells/mL, (f) no cells (normal saline). PBS : phosphate-buffered saline, hBM-MSCs : human bone marrow-derived mesenchymal stem cells, SPIO : superparamagnetic iron oxide, hMSC : human mesenchymal stem cell.
Mentions: MRI obtained at 6.3×104, 1.3×105, 2.5×105 and 5.0×105, cells showed that ferumoxide-labeling caused signals to become dark in a dose-dependent manner. Among the pulse sequences, SWI showed the maximum susceptibility effect of SPIO followed by T2*WI and T2WI. No significant susceptibility effect was noted in unlabeled hBM-MSCs or normal saline on MRI (Fig. 3).

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