Various Cell Populations Within the Mononuclear Fraction of Bone Marrow Contribute to the Beneficial Effects of Autologous Bone Marrow Cell Therapy in a Rodent Stroke Model.
Various Cell Populations Within the Mononuclear Fraction of Bone Marrow Contribute to the Beneficial Effects of Autologous Bone Marrow Cell Therapy in a Rodent Stroke Model.
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DOI：
10.1007/s12975-016-0462-x
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发表时间：
2016-08
影响因子：
6.9
通讯作者：
Savitz SI
中科院分区：
文献类型：
--
作者：
Yang B;Parsha K;Schaar K;Xi X;Aronowski J;Savitz SI
基于细胞的疗法，包括骨髓来源的单核细胞（MNCs），现在被广泛研究，因为它们的多效性和有希望的结果，以改善中风后的动物模型的恢复。与其他类型的细胞疗法不同，MNC是淋巴细胞、骨髓细胞、红细胞和干细胞群的混合物。哪种细胞群解释了MNC在中风恢复中的有益作用尚不清楚。在本文中，我们采用了一个小鼠中风模型与大脑中动脉闭塞（MCAo），并使用积极和消极的分选自体MNC的MAC，以确定哪些分数的MNC有助于他们的有益效果。我们在一项卒中后28天的长期观察研究中评估了MNCs内单个细胞谱系产生的神经功能恢复的益处。还比较了不同亚群之间的死亡率和炎症调节。我们进一步研究了在MNCs内存在不同细胞谱系的情况下激活的小胶质细胞所造成的神经毒性的影响。我们的结论是，髓系细胞谱系和干细胞/祖细胞似乎是MNCs内的重要组成部分，有助于改善中风后的结果。
Cell-based therapies including bone-marrow derived mononuclear cells (MNCs) are now widely being studied because of their pleotropic effects and promising results to improve recovery after stroke in animal models. Unlike other types of cell therapies, MNCs is a mixture of lymphoid, myeloid, erythroid, and stem cell populations. Which cell population(s) accounts for the beneficial effects of MNCs in stroke recovery is unclear. In this paper, we employed a mouse stroke model with middle cerebral artery occlusion (MCAo), and used positively and negatively sorted autologous MNCs by MACs to determine which fractions of the MNCs contribute to their beneficial effects. We evaluated the benefits of neurofunctional recovery produced by individual cell lineages within MNCs in a long-term observation study up to 28 days after stroke. Mortality and modulation of inflammation were also compared among different sub-populations. We further studied the impact of neurotoxicity posed by activated microglia in the presence of different cell lineages within MNCs. We concluded that myeloid cell lineage and stem cell/progenitors appear to be important components within MNCs that contribute to improved outcomes after stroke.