ARTEMIS: UC-MSCs After Mechanical Thrombectomy for Acute Ischemic Stroke (ARTEMIS)

- Scientific Rationale: Acute ischemic stroke results from an interruption of cerebral blood flow, causing ischemic injury and potentially persistent neurological disability. Mechanical thrombectomy restores blood flow by removing the occluding thrombus; however, successful reperfusion does not necessarily prevent secondary tissue injury or subsequent neurological impairment. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) possess immunomodulatory and tissue-repair properties that provide a scientific rationale for investigating their therapeutic potential following ischemic stroke. The safety and feasibility of intra-arterial administration after mechanical thrombectomy during the acute phase require further clinical evaluation.

- Study Overview and Procedures:

ARTEMIS (ARterial ThErapy with Mesenchymal stromal cells In Stroke) is a Phase 1 randomized, controlled clinical trial evaluating the safety and feasibility of intra-arterial administration of allogeneic UC-MSCs following mechanical thrombectomy. The study will include ten adults aged 18-70 years with imaging-confirmed acute ischemic stroke, a National Institutes of Health Stroke Scale (NIHSS) score of 6-20, and a prestroke modified Rankin Scale (mRS) score below 2. Participants must be eligible for mechanical thrombectomy within six hours of symptom onset and achieve successful reperfusion, defined as a modified Thrombolysis in Cerebral Infarction (mTICI) grade of 2b-3. Key exclusions include previous stroke, cerebellar or brainstem stroke, intracranial hemorrhage or major structural brain lesions, significant coagulation disorders, severe uncontrolled comorbidities, recent myocardial infarction, seizures, cancer, pregnancy or breastfeeding, contrast-agent allergy, and conditions that prevent informed participation or reliable follow-up. Written informed consent will be obtained from participants or their legally authorized representatives.

Participants will be randomly allocated in a 1:1 ratio to receive standard stroke care alone or standard care supplemented with cell administration. The randomization sequence will be generated using the Sealed Envelope platform, as specified in the study protocol.

In the intervention group, cell administration will take place after angiographic confirmation of successful reperfusion. The cells will be delivered through a microcatheter into the main artery supplying the infarcted territory. Repeat angiography will be performed after administration to assess for vascular occlusion or hemorrhage. Both groups will receive routine post-thrombectomy care and physical rehabilitation.

- Investigational Product:

The allogeneic UC-MSC product, called Whartocell®, is manufactured under Good Manufacturing Practice (GMP) conditions and has approval for cerebral palsy (CP) and osteoarthritis indications.

The investigational product consists of allogeneic mesenchymal stromal cells isolated from Wharton's jelly tissue obtained from donated full-term umbilical cords following the required consent procedures. Umbilical cord tissue will be collected under sterile conditions and processed to isolate the stromal cell population and will undergo product characterization and quality-control testing.

- Safety Monitoring:

Participants will undergo clinical monitoring throughout the study and follow-up period. Adverse events will be documented and evaluated for severity, duration, and potential relationship to the investigational product or study procedures. The protocol specifies the use of the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0), for safety monitoring.

Serious adverse events and suspected unexpected serious adverse reactions will be managed and reported according to the study protocol and applicable institutional requirements. Safety information will be reviewed by the clinical team and the Data and Safety Monitoring Board (DSMB), as specified in the protocol.

- Study Objectives:

This early-phase clinical investigation aims to establish preliminary evidence regarding the safety and feasibility of intra-arterial UC-MSC administration following mechanical thrombectomy during the acute phase of stroke. The findings may inform the design of subsequent clinical studies evaluating cell-based interventions for acute ischemic stroke. The study is exploratory and is not intended to establish definitive therapeutic efficacy.