Therapeutic benefit of intravenous transplantation of mesenchymal stem cells after experimental subarachnoid hemorrhage in rats.

Subarachnoid hemorrhage (SAH) usually occurs when an aneurysm ruptures and bleeds into the subarachnoid space. However, no information is available regarding the therapeutic potency of transplanted mesenchymal stem cells (MSCs) for SAH. Therefore, our aim was to investigate whether MSC transplantation therapy may cause stem cell activation and improve neurologic functional recovery after induction of SAH. Female rats were divided into 2 groups of SAH plus phosphate-buffered saline (PBS; control) and SAH plus MSCs (experimental). Both control and experimental groups received PBS or injection of 3 × 10(6) male rat MSCs labeled with bromodeoxyuridine (BrdU) into the tail vein 24 hours after SAH. All animals were killed 14 days after SAH. A behavioral test (Neurological Severity Score) was performed at 1, 7, and 14 days after SAH. Immunohistochemistry was used to identify MSCs and the cells derived from MSCs in brains with SAH. Terminal deoxynucleotidyltransferase mediated dUTP-biotin nick-end labeling was used to identify apoptotic cells. Significant functional recovery (P < .05) was found in SAH animals infused with MSCs compared with other rats. Significantly more BrdU-positive cells were located in the parietal lobe of MSC-treated than in PBS-treated animals. MSCs were also seen to differentiate into glial cells (GFAP), neurons (Neu-N), and endothelial cells (vWF), thereby enhancing neuroplastic effects in the injured brain. Significantly fewer apoptotic cells were found in insulted cerebral tissue in SAH plus MSC rats when compared with other groups. Intravenously transplanted MSCs improve functional recovery, reduce apoptosis, and enhance neuroplastic effects after SAH in animal models. This is a promising novel procedure to repair central nervous system damage after SAH, and may provide a new way to induce plasticity in the injured brain cells.

Khalili MA ，Anvari M ，Hekmati-Moghadam SH ，Sadeghian-Nodoushan F ，Fesahat F ，Miresmaeili SM ... -  《-》

Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat.

The present study investigates the induction of neurogenesis, reduction of apoptosis, and promotion of basic fibroblast growth factor (bFGF) expression as possible mechanisms by which treatment of stroke with bone marrow stromal cells (MSCs) improves neurological functional recovery. Additionally, for the first time, we treated cerebral ischemia in female rats with intraveneous administration of MSCs. Female rats were subjected to 2 hr of middle cerebral artery occlusion (MCAo), followed by an injection of 3 x 10(6) male (for Y chromosome labeling) rat MSCs or phosphate-buffered saline (PBS) into the tail vein 24 hr after MCAo. All animals received daily injection of bromodeoxyuridine (BrdU; 50 mg/kg, i.p.) for 13 days after treatment for identification of newly synthesized DNA. Animals were sacrificed at 14 days after MCAo. Behavioral tests (rotarod and adhesive-removal tests) were performed. In situ hybridization, immunohistochemistry, and terminal deoxynucleotidyltransferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) were performed to identify transplanted MSCs (Y chromosome), BrdU, bFGF, and apoptotic cells in the brain. Significant recovery of behavior was found in MSC-treated rats at 7 days in the somatosensory test and at 14 days in the motor test after MCAo compared with control, PBS-treated animals (P<.05). MSCs were found to survive and preferentially localize to the ipsilateral ischemic hemisphere. Significantly more BrdU-positive cells were located in the subventricular zone (P<.05), and significantly fewer apoptotic cells and more bFGF immunoreactive cell were found in the ischemic boundary area (P<.05) of MSC-treated rats than in PBS-treated animals. Here we demonstrate that intravenously administered male MSCs increase bFGF expression, reduce apoptosis, promote endogenous cellular proliferation, and improve functional recovery after stroke in female rats.

Chen J ，Li Y ，Katakowski M ，Chen X ，Wang L ，Lu D ，Lu M ，Gautam SC ，Chopp M ... -  《JOURNAL OF NEUROSCIENCE RESEARCH》

Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats.

Bao X ，Wei J ，Feng M ，Lu S ，Li G ，Dou W ，Ma W ，Ma S ，An Y ，Qin C ，Zhao RC ，Wang R ... -  《-》

Therapeutic effect of mesenchymal stem cells in rats with intracerebral hemorrhage: reduced apoptosis and enhanced neuroprotection.

Wang SP ，Wang ZH ，Peng DY ，Li SM ，Wang H ，Wang XH ... -  《-》

Therapeutic effect of human umbilical tissue-derived cell treatment in rats with experimental intracerebral hemorrhage.

The present study examines whether human umbilical tissue-derived cells (hUTC) have a neuro-restorative effect and improve functional recovery after intracerebral hemorrhage (ICH) in rats. Primary ICH was induced in male Wistar rats by stereotactic injection of 100μL of autologous blood into the striatal region adjacent to the subventricular zone. Briefly, the rats were randomly divided into six groups, each group was intravenously injected either with 2mL phosphate-buffered saline (PBS) or 3million hUTC in PBS at 1, 3 or 7days after ICH (n=8/group). To evaluate neurological functional outcome, each animal was subjected to the modified neurological severity score (mNSS) and corner turn tests at different time points after ICH. At four weeks post treatment, each group was anesthetized intraperitoneally, sacrificed, and brain tissues were processed histologically. Immunohistochemistry was employed to measure vascularity (vWF), neurogenesis (BrdU TUJ1, DCX and NeuN), synaptogenesis (synaptophysin) and apoptosis (TUNEL). The hUTC-treated animals showed significantly improved neurological functional outcomes as assessed by mNSS and corner turn tests at 14, 21 and 28days post-injection in each treatment group (P<0.05) as compared to the PBS controls. Animals treated with hUTC were seen to have significantly increased cell proliferation, vascularity and synaptogenesis, as well as reduced apoptosis in the hematoma rim compared to the corresponding control group (P<0.05). Intravenously infused hUTC have a beneficial effect after experimental ICH by functional and histochemical measurements of neural cell proliferation and synaptogenesis in the ICH border zone. This brain region also shows correlative evidence of neuronal recovery with increased vascularity.

Yang D ，Han Y ，Zhang J ，Seyda A ，Chopp M ，Seyfried DM ... -  《-》