Treatment Evaluation of Acute Stroke for Using in Regenerative Cell Elements

Inclusion Criteria:

• Japanese male or female patients 20 years of age or older;
• Clinical diagnosis of cerebral cortical ischemic stroke;
• Occurrence of an ischemic stroke with clear motor or speech deficit documented byNational Institutes of Health Stroke Scale (NIHSS) score of 8 to 20 (at the baselineassessment) that did not change by ≥4 points from the screening to the baselineassessment;
• Onset of ischemic stroke must have occurred within 18 to 36 hours prior to the startof administration of the investigational product;
• Confirmation of hemispheric cortical infarct with brain magnetic resonance imaging (MRI) including diffusion-weighted imaging with b-value of 1,000 demonstrating anacute lesion measuring ≥ 2.0 cm of longest diameter;
• A modified Rankin Scale (mRS) of 0 or 1, by either self-report or family report, priorto the onset of ischemic stroke;
• Female patients who meet either:
• Not pregnant, not breastfeeding/ interrupting breastfeeding, and not planning onbecoming pregnant during the trial;
• Not of childbearing potential, defined as one who has been postmenopausal for atleast 1 year, or has been surgically sterilized, or has had a hysterectomy atleast 3 months prior to the start of this trial; or
• If of childbearing potential, one who has agreed to follow investigator's adviceand use an effective contraceptive method up to the end of the trial. Effectivecontraceptive methods include contraceptive methods used consistently andcorrectly (oral contraceptives, intrauterine devices, diaphragm, or male orfemale condoms), abstinence, and a sterile sexual partner;
• Male patients with female partners of childbearing potential must agree to followinvestigator's advice and use adequate contraceptive methods (a combination of acondom and another form of contraception) up to the end of the trial if engaging insexual intercourse;
• Patients or legal representatives must freely sign the informed consent form after thenature of the trial and the disclosure of his/her data have been explained;
• Willing and able to comply with all aspects of the treatment and testing schedule; and
• Willing and able to return to the trial site for the post-treatment evaluations.

Exclusion Criteria:

• Presence of a lacunar, a lesion of ≤ 2.0 cm of longest diameter, or a brainsteminfarct on MRI as the etiology of symptoms of ischemic stroke;
• Reduced level of consciousness (score of 3 for item 1a of NIHSS);
• Occurrence of a hemorrhagic transformation as evidenced by computerized tomography (CT) or brain MRI scan that is clinically significant in the opinion of theinvestigator;
• Ipsilateral focal neurological deficits from prior lesions in the brain that wouldcomplicate evaluation;
• Experienced seizures since the onset of ischemic stroke;
• History of a neurological event such as stroke or clinically significant head traumawithin 6 months prior to the start of screening;
• Patients who both received tPA treatment and underwent mechanical reperfusion (patients are eligible for the trial if they had only one of them, tPA treatment ormechanical reperfusion);
• Uncontrolled hypertension, defined as persistent systolic blood pressure >220 mmHg ordiastolic blood pressure >120 mmHg, despite antihypertensive therapy;
• Blood glucose level <50 mg/dL or >350 mg/dL at baseline;
• Patients who have a significant comorbid medical condition(s), including, but notlimited to:
• Severe kidney disease requiring hemodialysis or peritoneal dialysis;
• Advanced liver disease such as hepatitis or liver cirrhosis;
• Severe congestive heart failure or history of ejection fraction <30%;
• Severe lung disease requiring home oxygen; or
• Active unstable angina requiring daily treatment with nitrates or othermedications;
• Known human immunodeficiency virus infection, ongoing systemic infection, severe localinfection or who are immunocompromised;
• Alzheimer's disease or other dementias, Parkinson's disease, or any other neurologicaldisorder that in the opinion of the trial doctor would affect their ability toparticipate in the trial or confound study assessments;
• History of malignant tumor(s) within 2 years of the onset of ischemic stroke, with theexception of adequately treated basal or squamous cell carcinoma of the skin;
• Contraindication for MRI such as implanted pacemakers or other metallic prosthesisincompatible with MRI, body weight, or claustrophobia;
• Thrombocytopenia (platelet count <100,000/mm3) or heparin-induced thrombocytopenia;
• Known allergy to human tissue or bovine or porcine products, or religious objectionsto biological products;
• Prior participation in another clinical trial involving investigationalpharmacological agents or devices within 30 days prior to providing consent to receivethe investigational product, or participation in investigational pharmacologicalagents, devices, or rehabilitation stroke recovery program is planned during thetrial;
• Other serious medical or psychiatric illness that is not adequately controlled and, inthe investigator's opinion, would not permit the subject to be managed according tothe protocol;
• Previous surgical removal of the spleen;
• Major fluctuation in neurological status since the onset of ischemic stroke indicatingprogression or expansion of ischemic stroke, or possible transient ischemic attack;
• Plan to have a neurovascular procedure (e.g., carotid endarterectomy, stent placement,etc.) within the first year following ischemic stroke; or
• Abnormal laboratory test results which investigators consider clinically significantand inappropriate for the trial.