1Institute of Advanced Biomedical Engineering and Science and.
2Department of Neurosurgery, Tokyo Women's Medical University; and.
J Neurosurg. 2019 Feb 22;132(2):442-455. doi: 10.3171/2018.11.JNS182331. Print 2020 Feb 1.
Stem cell therapy is a promising strategy for the treatment of severe cerebral ischemia. However, targeting sufficient grafted cells to the affected area remains challenging. Choosing an adequate transplantation method for the CNS appears crucial for this therapy to become a clinical reality. The authors used a scaffold-free cell sheet as a translational intervention. This method involves the use of cell sheet layers and allows the transplantation of a large number of cells, locally and noninvasively. The authors evaluated the effectiveness of allogeneic adipose tissue-derived mesenchymal stem cell sheets in a rat model of stroke.
The animals, subjected to middle cerebral artery occlusion, were randomly divided in two groups: one in which a cell sheet was transplanted and the other in which a vehicle was used (n = 10/group). Over a period of 14 days after transplantation, the animals' behavior was evaluated, after which brain tissue samples were removed and fixed, and the extent of angiogenesis and infarct areas was evaluated histologically.
Compared to the vehicle group, in the cell sheet group functional angiogenesis and neurogenesis were significantly increased, which resulted in behavioral improvement. Transplanted cells were identified within newly formed perivascular walls as pericytes, a proportion of which were functional. Newly formed blood vessels were found within the cell sheet that had anastomosed to the cerebral blood vessels in the host.
The transplantation approach described here is expected to provide not only a paracrine effect but also a direct cell effect resulting in cell replacement that protects the damaged neurovascular unit. The behavioral improvement seen with this transplantation approach provides the basis for further research on cell sheet-based regenerative treatment as a translational treatment for patients with stroke.
干细胞疗法是治疗严重脑缺血的一种很有前途的策略。然而，将足够数量的移植细胞靶向到受影响的区域仍然具有挑战性。选择一种合适的中枢神经系统移植方法对于使该疗法成为临床现实至关重要。作者使用无支架细胞片作为转化干预措施。该方法涉及使用细胞片层，并允许局部和非侵入性地移植大量细胞。作者在大鼠中风模型中评估了同种异体脂肪组织来源间充质干细胞片的有效性。
动物接受大脑中动脉闭塞后，随机分为两组：一组移植细胞片，另一组使用载体（每组 n = 10）。在移植后 14 天内，评估动物的行为，然后取出脑组织样本并固定，评估血管生成和梗塞面积的组织学程度。
与载体组相比，细胞片组的功能性血管生成和神经发生明显增加，导致行为改善。在新形成的血管周围壁内鉴定出移植细胞作为周细胞，其中一部分具有功能性。在与宿主脑血管吻合的细胞片中发现了新形成的血管。
这里描述的移植方法预计不仅提供旁分泌作用，而且提供直接的细胞作用，从而进行细胞替代，保护受损的神经血管单元。这种移植方法所观察到的行为改善为基于细胞片的再生治疗作为中风患者的转化治疗的进一步研究提供了基础。
