Comparative Analysis of the Results of Stroke Treatment With Multiple Administrations of Wharton's Jelly Mesenchymal Stem Cells-Derived HE-ATMP and Standard Conservative Treatment: Case Series Study.

Stroke remains still the leading cause of long-term disability worldwide. Although interventions such as early reperfusion, intravenous thrombolysis, and endovascular revascularization have shown neurological benefit in stroke patients, there is still lack of effective treatment enabling regeneration of nervous tissue after cerebral ischemic episodes. Cell therapy is an evolving opportunity for stroke survivors with residual neurological deficits. The purpose of this study was to evaluate safety and potential efficacy of multiple administration of Hospital Exemption-Advanced Therapy Medicinal Product (HE-ATMP) comprising 3 × 107 Wharton's jelly mesenchymal stem cells (WJMSCs). A study group was composed of six patients-three women and three men. The patients were qualified to the treatment with diagnosis of chronic stroke (2-24 months after cerebral ischemic episode), during 2 years. All the patients undergone repeated rounds of HE-ATMP administration to the CSF (cerebrospinal fluid) via lumbar puncture. The control group consisted of six patients (two women and four men) who experienced stroke, treated at the same time (follow-up period: 24 months) using standard treatment methods, without endovascular treatment. To evaluate the results of the therapy, we used both impairment scales [National Institutes of Health Stroke Score (NIHSS)] and functional outcomes scales [Modified Rankin Scale (MRS) and Barthel Index (BI)]. In four patients, who received at least three repeated rounds of HE-ATMP, we reported neurological improvement and reduction of functional neurodeficiency. The biggest improvement concerned the reduction of speech disorders in two cases; significant improvement in the field of motor skills in three patients and reduction of apraxia and improvement of logical communication skills in two patients were also reported. All the patients became more independent. Significant improvement of the neurological condition using the same scales was registered only in two patients from the control group. We did not report any adverse events in the treated group during follow-up. At 1-year follow-up, we demonstrate safety and beneficial effect of WJMSC transplantation including neurological improvement and reduction of functional neurodeficiency. We are aware that the samples size of this study is relatively small. The treatment regimen needs to be further tested in larger group of patients.

Use of Multiple Wharton Jelly Mesenchymal Stem Cell Transplants in Treatment of Incomplete Spinal Cord Injury: A Case Report.

Interruption of spinal cord continuity remains an incurable condition that leads to functional loss below the lesion level. Effective treatment to enable spinal cord regeneration is lacking, although cell therapy is an evolving opportunity. Therefore, the purpose of this study was to evaluate the safety and potential efficacy of multiple Wharton jelly mesenchymal stem cell transplants in a patient with a spinal cord injury. A patient with incomplete spinal cord interruption at the T11 to T12 vertebrae was enrolled in experimental therapy. The patient scored A/B on the ASIA scale (developed by the American Spinal Injury Association) with deep paraparesis and sphincter palsy. However, full ability to fix the patient's trunk upon admission was confirmed. Bilateral axonal damage of motor and sensory neural fibers of lower extremities was confirmed with electromyography and electroneurography. One year of standard therapy did not bring any positive results. The patient underwent 5 rounds of Wharton jelly mesenchymal stem cell transplants every 3 months (total treatment time of 18 months). There were no complications connected with therapy during the 18- month follow-up. Continuous neurological and quality of life improvements were seen after every transplant. The patient's ASIA score changed from A/B to C/D and from 112 to 231 points. The sensation level decreased from the T12 to L3 to L4 level. The patient regained bladder control and anal sensation. Muscle strength at the left lower extremity improved. The patient gained the ability to stand in a standing frame and walk with an orthosis. Neurophysiological examinations objectively confirmed the improvement. Magnetic resonance imaging demonstrated no changes in the spinal cord signal. The treatment demonstrated an objective improvement that could be used for patients with chronic thoracic incomplete spinal cord injury.