人诱导多能干细胞可改善中风损伤老龄大鼠的恢复情况。

Human induced pluripotent stem cells improve recovery in stroke-injured aged rats.

作者信息

Tatarishvili Jemal, Oki Koichi, Monni Emanuela, Koch Philipp, Memanishvili Tamar, Buga Ana-Maria, Verma Vivek, Popa-Wagner Aurel, Brüstle Oliver, Lindvall Olle, Kokaia Zaal

机构信息

Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, Lund, Sweden.

Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn and Hertie Fundation, Bonn, Germany.

出版信息

Restor Neurol Neurosci. 2014;32(4):547-58. doi: 10.3233/RNN-140404.

DOI:10.3233/RNN-140404

PMID:24916776

Abstract

PURPOSE

Induced pluripotent stem cells (iPSCs) improve behavior and form neurons after implantation into the stroke-injured adult rodent brain. How the aged brain responds to grafted iPSCs is unknown. We determined survival and differentiation of grafted human fibroblast-derived iPSCs and their ability to improve recovery in aged rats after stroke.

METHODS

Twenty-four months old rats were subjected to 30 min distal middle cerebral artery occlusion causing neocortical damage. After 48 h, animals were transplanted intracortically with human iPSC-derived long-term neuroepithelial-like stem (hiPSC-lt-NES) cells. Controls were subjected to stroke and were vehicle-injected.

RESULTS

Cell-grafted animals performed better than vehicle-injected recipients in cylinder test at 4 and 7 weeks. At 8 weeks, cell proliferation was low (0.7 %) and number of hiPSC-lt-NES cells corresponded to 49.2% of that of implanted cells. Transplanted cells expressed markers of neuroblasts and mature and GABAergic neurons. Cell-grafted rats exhibited less activated microglia/macrophages in injured cortex and neuronal loss was mitigated.

CONCLUSIONS

Our study provides the first evidence that grafted human iPSCs survive, differentiate to neurons and ameliorate functional deficits in stroke-injured aged brain.

摘要

目的

诱导多能干细胞（iPSC）植入成年中风损伤啮齿动物脑内后可改善行为并形成神经元。老年大脑对移植的iPSC如何反应尚不清楚。我们确定了移植的人成纤维细胞来源的iPSC的存活和分化情况，以及它们改善老年中风大鼠恢复的能力。

方法

对24个月大的大鼠进行30分钟的大脑中动脉远端闭塞，造成新皮质损伤。48小时后，将人iPSC来源的长期神经上皮样干细胞（hiPSC-lt-NES）细胞皮质内移植到动物体内。对照组进行中风手术并注射赋形剂。

结果

在4周和7周的圆柱体试验中，细胞移植动物的表现优于注射赋形剂的受体。在8周时，细胞增殖率较低（0.7%），hiPSC-lt-NES细胞数量相当于植入细胞数量的49.2%。移植细胞表达神经母细胞、成熟神经元和GABA能神经元的标志物。细胞移植大鼠损伤皮质中活化的小胶质细胞/巨噬细胞较少，神经元损失减轻。