自体间充质干细胞脑内移植可改善慢性缺血性中风大鼠模型的功能恢复。
Intracerebral Transplantation of Autologous Mesenchymal Stem Cells Improves Functional Recovery in a Rat Model of Chronic Ischemic Stroke.
发表日期:2023 Nov 02
作者:
Max I Myers, Kevin J Hines, Andrew Gray, Gabrielle Spagnuolo, Robert Rosenwasser, Lorraine Iacovitti
来源:
Stem Cell Research & Therapy
摘要:
虽然中风急性期有治疗方法,但慢性梗塞和长期残疾患者的选择有限。同种异体间充质干细胞(alloMSCs)有望在缺血性损伤后不久治疗中风。然而,没有关于使用自体间充质干细胞(autoMSCs)在患有慢性梗塞的大鼠脑内输送的信息。在这项研究中,大鼠接受大脑中动脉闭塞(MCAO)以诱导中风,然后在封闭的生物反应器中进行骨髓抽吸和 MSC 扩增。 4 周后,获得脑部 MRI,并将 autoMSC(1 × 106、2.5 × 106 或 5 × 106;各 n = 6)立体定向注射到梗塞周围,并与对照(仅 MCAO;MCAO PBS;n = 6)进行比较。 -9)。使用改良的神经严重程度评分(mNSS)评估行为。为了进行比较,另一组 MCAO 大鼠被植入了来自健康大鼠的 2.5 × 106 个同种异体间充质干细胞。 60 天后,所有剂量的 autoMSC 的感觉运动功能均产生显着改善 (54-70%)。相比之下,alloMSC 仅改善了 31.7%,与 PBS 对照中的 30% 相似。在整个移植后期间,仅在植入部位发现了量子点标记的自体/同种异体间充质干细胞,移植的间充质干细胞的 MRI 或 Ki67 染色显示没有肿瘤形成。 MSC 治疗后观察到每搏输出量存在微小差异,而胼胝体宽度没有差异。梗死周围中风诱导的神经胶质反应性是持久的,并且自体/同种异体间充质干细胞移植不会减弱。这些研究表明,与异体间充质干细胞相比,自体间充质干细胞的脑内移植可能是慢性中风的一种有前景的治疗方法。© 2023。作者。
While treatments exist for the acute phase of stroke, there are limited options for patients with chronic infarcts and long-term disability. Allogenic mesenchymal stem cells (alloMSCs) show promise for the treatment of stroke soon after ischemic injury. There is, however, no information on the use of autologous MSCs (autoMSCs), delivered intracerebrally in rats with a chronic infarct. In this study, rats underwent middle cerebral artery occlusion (MCAO) to induce stroke followed by bone marrow aspiration and MSC expansion in a closed bioreactor. Four weeks later, brain MRI was obtained and autoMSCs (1 × 106, 2.5 × 106 or 5 × 106; n = 6 each) were stereotactically injected into the peri-infarct and compared to controls (MCAO only; MCAO + PBS; n = 6-9). Behavior was assessed using the modified neurological severity score (mNSS). For comparison, an additional cohort of MCAO rats were implanted with 2.5 × 106 alloMSCs generated from a healthy rat. All doses of autoMSCs produced significant improvement (54-70%) in sensorimotor function 60 days later. In contrast, alloMSCs improved only 31.7%, similar to that in PBS controls 30%. Quantum dot-labeled auto/alloMSCs were found exclusively at the implantation site throughout the post-transplantation period with no tumor formation on MRI or Ki67 staining of engrafted MSCs. Small differences in stroke volume and no differences in corpus callosum width were observed after MSC treatment. Stroke-induced glial reactivity in the peri-infarct was long-lasting and unabated by auto/alloMSC transplantation. These studies suggest that intracerebral transplantation of autoMSCs as compared to alloMSCs may be a promising treatment in chronic stroke.© 2023. The Author(s).