Department of Children's Neurosurgery, Institute of Pediatrics, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland.
Department of Laboratory Medicine, Andrzej Frycz-Modrzewski Cracow University, Cracow, Poland.
Cell Transplant. 2023 Jan-Dec;32:9636897231195145. doi: 10.1177/09636897231195145.
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 × 10 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.
中风仍然是全球导致长期残疾的主要原因。尽管早期再灌注、静脉溶栓和血管内血管重建等干预措施已显示出对中风患者的神经益处，但仍然缺乏有效的治疗方法，无法实现脑缺血发作后神经组织的再生。细胞疗法为有残留神经功能缺陷的中风幸存者提供了一个不断发展的机会。本研究的目的是评估多次给药包含 3×10 个 Wharton 胶间充质干细胞（WJMSCs）的医院豁免先进治疗药物产品（HE-ATMP）的安全性和潜在疗效。研究组由 6 名患者组成-3 名女性和 3 名男性。这些患者符合慢性中风的治疗条件（脑缺血发作后 2-24 个月），治疗时间为 2 年。所有患者均通过腰椎穿刺将 HE-ATMP 重复给药至脑脊液（CSF）。对照组由 6 名患者组成（2 名女性和 4 名男性），他们在同一时间经历了中风，同时采用标准治疗方法治疗（随访期：24 个月），未进行血管内治疗。为了评估治疗结果，我们同时使用了损伤量表[国立卫生研究院中风量表（NIHSS）]和功能结局量表[改良 Rankin 量表（MRS）和巴氏指数（BI）]。在至少接受了 3 次重复 HE-ATMP 治疗的 4 名患者中，我们报告了神经功能改善和功能神经缺损减少。最大的改善涉及到 2 例言语障碍的减少；3 名患者的运动技能显著改善，2 名患者的失用症减少，逻辑沟通技能改善；所有患者都变得更加独立。对照组的 2 名患者的神经状况也有显著改善。在随访期间，我们未在治疗组报告任何不良事件。在 1 年随访时，我们证明了 WJMSC 移植的安全性和有益效果，包括神经功能改善和功能神经缺损减少。我们意识到本研究的样本量相对较小。该治疗方案需要在更大的患者群体中进一步测试。
