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 ... -  《-》

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 ... -  《-》

Lipoaspirate-derived adult mesenchymal stem cells improve functional outcome during intracerebral hemorrhage by proliferation of endogenous progenitor cells stem cells in intracerebral hemorrhages.

Fatar M ，Stroick M ，Griebe M ，Marwedel I ，Kern S ，Bieback K ，Giesel FL ，Zechmann C ，Kreisel S ，Vollmar F ，Alonso A ，Back W ，Meairs S ，Hennerici MG ... -  《-》

Lithium fails to enhance neurogenesis in subventricular zone and dentate subgranular zone after intracerebral hemorrhage in rats.

Kang K ，Kim YJ ，Lee SH ，Yoon BW ... -  《-》