Neuroscience Research Unit, Neuroscience Rafael del Pino Chair, and Neurosurgical Service, Hospital Puerta de Hierro-Majadahonda, Autonomous University, Madrid, Spain.
Cytotherapy. 2013 Jan;15(1):33-43. doi: 10.1016/j.jcyt.2012.10.005.
Cell therapy using bone marrow stromal cells (BMSCs) has been considered a promising strategy for neurologic sequelae after intracerebral hemorrhage (ICH). However, after intracerebral administration of BMSCs, most of the cells die, partly because of the absence of extracellular matrix. Intracerebral transplantation of BMSCs, supported in a platelet-rich plasma (PRP) scaffold, optimizes this type of cell therapy.
ICH was induced by stereotactic injection of 0.5 IU of collagenase type IV in the striatum of adult Wistar rats (n = 40). Two months later, the rats were subjected to intracerebral administration of 5 × 10(6) allogeneic BMSCs embedded in a PRP scaffold (n = 10), 5 × 10(6) allogeneic BMSCs in saline (n = 10), PRP-derived scaffold only (n = 10) or saline only (n = 10). Functional improvements in each group over the next 6 months were assessed using Rotarod and Video-Tracking-Box tests. Endogenous neurogenesis and survival of transplanted BMSCs were examined at the end of follow-up.
Our study demonstrated neurologic improvement after BMSC transplantation and significantly better functional improvement for the group of animals that received BMSCs in the PRP-derived scaffold compared with the group that received BMSCs in saline. Histologic results showed that better functional outcome was associated with strong activation of endogenous neurogenesis. After intracerebral administration of BMSCs, donor cells were integrated in the injured tissue and showed phenotypic expression of glial fibrillary acidic protein and neuronal nucleus.
PRP-derived scaffolds increase the viability and biologic activity of BMSCs and optimize functional recovery when this type of cell therapy is applied after ICH.
骨髓基质细胞(BMSCs)的细胞治疗被认为是治疗脑出血(ICH)后神经后遗症的一种很有前途的策略。然而,在脑内给予 BMSCs 后,大多数细胞死亡,部分原因是缺乏细胞外基质。富含血小板的血浆(PRP)支架支持脑内 BMSCs 移植,优化了这种细胞治疗。
立体定向注射胶原酶 IV 0.5 IU 诱导成年 Wistar 大鼠 ICH(n = 40)。2 个月后,将大鼠脑内给予 5 × 10(6)异体 BMSCs 嵌入 PRP 支架(n = 10)、5 × 10(6)异体 BMSCs 生理盐水(n = 10)、PRP 衍生支架仅(n = 10)或生理盐水仅(n = 10)。在接下来的 6 个月内,使用旋转棒和视频跟踪箱测试评估每组的功能改善情况。在随访结束时检查内源性神经发生和移植 BMSCs 的存活情况。
我们的研究表明,BMSC 移植后神经功能改善,与接受生理盐水 BMSCs 的组相比,接受 PRP 衍生支架中 BMSCs 的组的功能改善更为明显。组织学结果表明,更好的功能结果与内源性神经发生的强烈激活有关。脑内给予 BMSCs 后,供体细胞整合在损伤组织中,并表现出神经胶质纤维酸性蛋白和神经元核的表型表达。
PRP 衍生支架增加了 BMSCs 的活力和生物学活性,并优化了 ICH 后应用这种细胞治疗的功能恢复。