In subacute and chronic phases of the stroke, there are no therapeutics available at present to promote functional recovery. Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) are one of the candidate cell types for treating subacute-phase stroke. The benefits of cell-based therapy largely depend on the migratory capacity of products administered, as well as their potential for engraftment in targeted tissues and paracrine activities. Timing and delivery modes may also influence the outcomes of stem-cell therapy. Still, the functional recuperative effects of differing hUC-MSC delivery modes, about cell replacement and cell-to-cell paracrine activity levels, have yet to be clarified in subacute phases of stroke.This study was conducted to compare the therapeutic effects of various delivery routes when administering Good Manufacturing Practice (GMP)-grade hUC-MSCs in a rodent model of subacute-phase stroke. Cell aliquots (1 × 10⁶) were given to rats as intravenous (IV) injections or intracerebral (IC) transplants 1 week after middle cerebral artery occlusion (MCAo). Transplanted rats were examined up to 7 weeks later using various behavioral tests and immunohistochemical analyses. Most IC-transplanted cells survived for short periods (i.e., <4 weeks after receipt) and gradually disappeared, whereas IV-injected cells were undetectable in the brain at the same time points (i.e., 3 days, 4 weeks, or 7 weeks after injection). Although short-lived, IC-transplanted cells effectively improved behavioral deficits, serving to reduce infarct volumes and glial scar formation, increase subventricular counts of proliferating neuroblasts, and promote cerebrovascular ingrowth in ischemic penumbra regions. IV injection, however, failed to improve behavioral function or histologic parameters during the same 7-week time frame. These findings overall suggest that IC transplantation is preferable to IV injection for delivery of hUC-MSCs during subacute phases of stroke.

在中风的亚急性和慢性阶段，目前没有可用于促进功能恢复的疗法。人脐带间充质基质细胞（hUC-MSC）是治疗亚急性期中风的候选细胞类型之一。基于细胞的疗法的优势在很大程度上取决于所施用产品的迁移能力，以及它们植入目标组织和旁分泌活动的潜力。时间安排和分娩方式也可能影响干细胞治疗的结果。尽管如此，在卒中的亚急性阶段，关于细胞置换和细胞间旁分泌活性水平的不同hUC-MSC传递方式的功能性调理作用尚未阐明。进行这项研究的目的是在亚急性期中风的啮齿动物模型中比较在“良好生产规范”（GMP）级hUC-MSCs给药后各种给药途径的治疗效果。细胞等分试样（1×10⁶）在大脑中动脉闭塞（MCAo）后1周以静脉注射（IV）或脑内（IC）移植的形式给予大鼠。使用各种行为测试和免疫组化分析，对移植的大鼠进行长达7周的检查。大多数植入IC的细胞在短时间内（即接收后<4周）存活并逐渐消失，而在同一时间点（即3天，4周或7周后）在大脑中未检测到静脉注射的细胞注射）。尽管IC移植的细胞寿命短，但可以有效地改善行为缺陷，从而减少梗塞体积和神经胶质瘢痕形成，增加正在增殖的成神经细胞的脑室下计数，并促进缺血半影区域的脑血管向内生长。但是，静脉注射 在相同的7周时间内未能改善行为功能或组织学参数。这些发现总体上表明，在中风的亚急性期中，IC移植优于静脉注射，以递送hUC-MSC。