Mahmood Asim, Lu Dunyue, Lu Mei, Chopp Michael
Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan 48202, USA.
Neurosurgery. 2003 Sep;53(3):697-702; discussion 702-3. doi: 10.1227/01.neu.0000079333.61863.aa.
We investigated the effect of human bone marrow stromal cells (hMSCs) administered intravenously on functional outcome after traumatic brain injury in adult rats.
hMSCs were harvested from three human donors. A controlled cortical impact was delivered to 27 adult male rats to induce traumatic brain injury, and 24 hours after injury, hMSCs were injected into the tail veins of the rats (n = 18). These rats were divided into two groups: Group 1 was administered 1 x 10(6) hMSCs, and Group 2 was administered 2 x 10(6) hMSCs. Group 3 (control) rats received saline intravenously. Neurological function was evaluated according to the rotarod test and modified neurological severity score. All rats were killed 1 month after injury, and immunohistochemical staining was performed on the brain sections to identify donor hMSCs. To study the phenotypic differentiation of hMSCs, coronal brain sections were stained for neuronal (Tuj1) and astrocytic (glial fibrillary acidic protein) markers.
Treatment with 2 x 10(6) hMSCs significantly improved the rats' functional outcomes (P < 0.05). The transplanted cells successfully migrated into injured brain and were preferentially localized around the injury site. Some of the donor cells also expressed the neuronal and astrocytic markers.
These data suggest that hMSCs may be a potential therapy for patients who have sustained traumatic brain injuries.
我们研究了静脉注射人骨髓间充质干细胞(hMSCs)对成年大鼠创伤性脑损伤后功能结局的影响。
从三名人类供体中采集hMSCs。对27只成年雄性大鼠进行控制性皮质撞击以诱导创伤性脑损伤,损伤后24小时,将hMSCs注入大鼠尾静脉(n = 18)。这些大鼠分为两组:第1组给予1×10⁶个hMSCs,第2组给予2×10⁶个hMSCs。第3组(对照组)大鼠静脉注射生理盐水。根据转棒试验和改良神经功能严重程度评分评估神经功能。所有大鼠在损伤后1个月处死,对脑切片进行免疫组织化学染色以鉴定供体hMSCs。为研究hMSCs的表型分化,对冠状脑切片进行神经元(Tuj1)和星形胶质细胞(胶质纤维酸性蛋白)标志物染色。
用2×10⁶个hMSCs治疗显著改善了大鼠的功能结局(P < 0.05)。移植的细胞成功迁移到损伤的大脑中,并优先定位在损伤部位周围。一些供体细胞还表达了神经元和星形胶质细胞标志物。
这些数据表明,hMSCs可能是创伤性脑损伤患者的一种潜在治疗方法。