Olstorn Havard, Moe Morten C, Røste Geir K, Bueters Tjerk, Langmoen Iver A
Vilhelm Magnus Center, Institute for Surgical Research, and Department of Neurosurgery, Ullevål University Hospital and Rikshospitalet, University of Oslo, Norway.
Neurosurgery. 2007 Jun;60(6):1089-98; discussion 1098-9. doi: 10.1227/01.NEU.0000255461.91892.0D.
To investigate the migration, proliferation, and differentiation of stem cells and neural progenitor cells (NPCs) from the adult human brain after transplantation into adult rodent brains.
Adult human NPCs were obtained from temporal lobe specimens removed because of medical intractable epilepsy. The cells were transplanted into the posterior periventricular region above the hippocampus in the brains of either healthy adult rats (control) or rats with selective injury of the hippocampal CA1 region (global ischemia).
In the control animals, grafted cells were mainly distributed from the site of transplantation toward the midline along white matter tracts. The density of transplanted cells elsewhere, including the hippocampus, was low and apparently random. In animals with CA1 damage, NPCs showed targeted migration into the injured area. Cell survival at 10 weeks was 4.7 +/- 0.3% (control, n = 3) and 3.7 +/- 1.1% (ischemia, n = 3); at 16 weeks, cell survival was 3.4 +/- 0.6% (control, n = 2) and 7.2 +/- 1.5% (ischemia, n = 2), i.e., comparable to what has been observed earlier when transplanting embryonic tissue into the human brain or progenitor cells between inbred rats. The number of dividing cells decreased with time. Sixteen weeks after transplantation, 4 +/- 1% (n = 4) of the cells showed proliferative activity. We did not observe signs of tumor formation or aberrant cell morphology. Neuronal differentiation was much slower than what has been observed earlier in vitro or after transplantation to the developing nervous system, and 16 weeks after transplantation many surviving cells were still in maturation.
The present study shows that adult human NPCs survive, show targeted migration, proliferate, and differentiate after grafting into the adult rat brain.
研究成人脑中的干细胞和神经祖细胞（NPCs）移植到成年啮齿动物脑内后的迁移、增殖和分化情况。
成人NPCs取自因药物难治性癫痫而切除的颞叶标本。将这些细胞移植到健康成年大鼠（对照组）或海马CA1区有选择性损伤（全脑缺血）的大鼠脑内海马上方的脑室后区。
在对照动物中，移植细胞主要沿着白质束从移植部位向中线分布。包括海马在内的其他部位移植细胞密度较低且分布明显随机。在CA1区受损的动物中，NPCs表现出向损伤区域的靶向迁移。10周时细胞存活率为4.7±0.3%（对照组，n = 3）和3.7±1.1%（缺血组，n = 3）；16周时，细胞存活率为3.4±0.6%（对照组，n = 2）和7.2±1.5%（缺血组，n = 2），即与之前将胚胎组织移植到人类脑内或近交系大鼠之间移植祖细胞时观察到的情况相当。分裂细胞数量随时间减少。移植16周后，4±1%（n = 4）的细胞表现出增殖活性。我们未观察到肿瘤形成迹象或异常细胞形态。神经元分化比之前在体外或移植到发育中的神经系统后观察到的要慢得多，移植16周后许多存活细胞仍处于成熟过程中。
本研究表明，成人NPCs移植到成年大鼠脑内后能够存活、表现出靶向迁移、增殖和分化。
