Effects of intravenous administration of human bone marrow stromal cells after intracerebral hemorrhage in rats

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The goal of this study was to investigate whether human bone marrow stromal cells (hBMSCs) administered by intravenous injection have a beneficial effect on outcome after intracerebral hemorrhage (ICH) in rats.


An ICH was induced in 54 adult male Wistar rats by a stereotactically guided injection of autologous blood into the right striatum. Intravenous infusion of the hBMSCs (3, 5, or 8 million cells) was performed 1 day after ICH, and for each dose group there was a control group that received injections of vehicle. Neurological function, which was evaluated using the Neurological Severity Score (NSS) and the corner turn test, was tested before and at 1, 7, and 14 days after ICH. After 14 days of survival, the area of encephalomalacia was calculated and histochemical labeling was performed.

For all three groups, there were no statistical differences in either the NSS or corner turn tests after 1 day. After 7 and 14 days, however, the three groups that received the hBMSCs showed significant improvement in functional scores compared with the control group. In addition, after 14 days there was significantly more striatal tissue loss in the placebo groups compared with each of the three treatment groups. The region of injury in the treated animals demonstrated a significantly increased presence of hBMSCs, immature neurons, neuronal migration, synaptogenesis, and newly formed DNA.


Intravenous administration of hBMSCs significantly improves neurological function in rats subjected to ICH. This improvement in the treated animals is associated with reduced tissue loss and increased local presence of the hBMSCs, mitotic activity, immature neurons, synaptogenesis, and neuronal migration.

Abbreviations used in this paper: BrdU = bromodeoxyuridine; DCX = doublecortin; hBMSC = human bone marrow stromal cell; ICH = intracerebral hemorrhage; mAb = monoclonal antibody; NSS = Neurological Severity Score; PBS = phosphate-buffered saline; SVZ = subventricular zone; TUJ1 = mAb Class III beta-tubulin isotype.

Article Information

Address reprint requests to: Donald Seyfried, M.D., Department of Neurosurgery, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, Michigan 48202. email: nsdos@neuro.hfh.edu.

© AANS, except where prohibited by US copyright law.



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    Bar graphs showing results of neurological functional assessment according to the NSS (left) and the corner turn test (right) for control and treatment groups of rats (injection of vehicle or 3, 5, or 8 million hBMSCs) 1 day before and 7 and 14 days after ICH. Abbreviations: D = day; n = number of rats; SEM = standard error of the mean.

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    Bar graph showing area of tissue loss in the region of the ICH, expressed as a percentage of the normal hemisphere for control and treatment groups of rats (injection of vehicle or 3, 5, or 8 million hBMSCs).

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    Photomicrographs and bar graphs showing values for DCX, mAb (MAB) 1281, BrdU, synaptophysin, and TUJ1 immunohistochemical labeling data for the three treatment (injection of 3, 5, and 8 million hBMSCs [hMSCs]) and control groups of rats. Arrows indicate cells or regions with positive staining. Original magnifications × 100 (panel with BrdU staining) and × 200 (all other panels).

  • View in gallery

    Photomicrograph showing BrdU colocalizing with TUJ1 in a subpopulation of cells near the injury zone. Arrow indicates cells with positive staining. Original magnification × 40.



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