Zhang Jing, Li Yi, Chen Jieli, Yang Maozhou, Katakowski Mark, Lu Mei, Chopp Michael
Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
Brain Res. 2004 Dec 24;1030(1):19-27. doi: 10.1016/j.brainres.2004.09.061.
Human bone marrow stromal cells (hMSCs) enhance neurological recovery after stroke in rodents, possibly via induction of growth factors. We therefore elected to test the effects of hMSC treatment on insulin-like growth factor 1 (IGF-1), which plays an important role in growth, development, neuroprotection and repair in the adult. Rats (n=57) were subjected to permanent middle cerebral artery occlusion (MCAo) and injected intravenously with 3 x 10(6) hMSCs or phosphate-buffered saline (PBS) at 1 day after MCAo. Functional outcome was measured after MCAo using a modified Neurological Severity Score (mNSS). Gene expression of IGF-1 and IGF-1 receptor (IGF-1R) in the ischemic brain tissue were measured at 2 and 7 days after MCAo using reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry was performed to measure the expression of bromodeoxyuridine (BrdU), doublecortin (DCX), IGF-1 and IGF-1R at 7, 14 and 30 days after MCAo. Treatment of MCAo with hMSCs significantly improved functional recovery from 14 to 30 days. MAB1281-labeled hMSCs entered the ischemic brain and increased time-dependently. hMSC treatment significantly increased IGF-1 mRNA and BrdU(+), DCX(+), IGF-1(+) and IGF-1R(+) cells compared to PBS-treated rats (p<0.05). The percentage of BrdU(+) or DCX(+) cells colocalized with IGF-1 increased in the hMSC-treated rats compared to the PBS-treated rats (p<0.05). IGF-1 and IGF-1R may contribute to improved functional recovery and increased neurogenesis after treatment of stroke with hMSCs.
人骨髓基质细胞（hMSCs）可促进啮齿动物中风后的神经功能恢复，可能是通过诱导生长因子实现的。因此，我们选择测试hMSC治疗对胰岛素样生长因子1（IGF-1）的影响，IGF-1在成体的生长、发育、神经保护和修复中发挥着重要作用。将57只大鼠进行永久性大脑中动脉闭塞（MCAo），并在MCAo后1天经静脉注射3×10⁶个hMSCs或磷酸盐缓冲盐水（PBS）。MCAo后使用改良神经功能缺损评分（mNSS）测量功能结局。在MCAo后2天和7天，使用逆转录聚合酶链反应（RT-PCR）测量缺血脑组织中IGF-1和IGF-1受体（IGF-1R）的基因表达。在MCAo后7天、14天和30天进行免疫组织化学检测，以测量溴脱氧尿苷（BrdU）、双皮质素（DCX）、IGF-1和IGF-1R的表达。hMSCs治疗MCAo可在14至30天显著改善功能恢复。MAB1281标记的hMSCs进入缺血脑并随时间增加。与PBS处理的大鼠相比，hMSC治疗显著增加了IGF-1 mRNA以及BrdU（+）、DCX（+）、IGF-1（+）和IGF-1R（+）细胞（p<0.05）。与PBS处理的大鼠相比，hMSC治疗的大鼠中与IGF-1共定位的BrdU（+）或DCX（+）细胞百分比增加（p<0.05）。IGF-1和IGF-1R可能有助于hMSCs治疗中风后功能恢复的改善和神经发生的增加。
