Long-Distance Growth and Connectivity of Neural Stem Cells after Severe Spinal Cord Injury

被引：743

作者：

Lu, Paul ^{[1
,3
]}

Wang, Yaozhi ^{[1
]}

Graham, Lori ^{[1
]}

McHale, Karla ^{[1
]}

Gao, Mingyong ^{[1
]}

Wu, Di ^{[1
]}

Brock, John ^{[1
]}

Blesch, Armin ^{[1
,6
]}

Rosenzweig, Ephron S. ^{[1
]}

Havton, Leif A. ^{[4
,5
]}

Zheng, Binhai ^{[1
]}

Conner, James M. ^{[1
]}

Marsala, Martin ^{[2
]}

Tuszynski, Mark H. ^{[1
,3
]}

机构：

[1] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Anesthesiol, La Jolla, CA 92093 USA

[3] Vet Adm Med Ctr, San Diego, CA 92161 USA

[4] Univ Calif Irvine, Dept Anesthesiol & Perioperat Care, Reeve Irvine Res Ctr, Irvine, CA 92697 USA

[5] Univ Calif Irvine, Dept Anat & Neurobiol, Reeve Irvine Res Ctr, Irvine, CA 92697 USA

[6] Univ Heidelberg Hosp, Spinal Cord Injury Ctr, D-69120 Heidelberg, Germany

来源：

CELL | 2012年 / 150卷 / 06期

关键词：

CENTRAL-NERVOUS-SYSTEM; PROMOTE AXONAL REGENERATION; ADULT-RAT; NEUROTROPHIC FACTORS; FUNCTIONAL RECOVERY; WHITE-MATTER; NEURONS; FETAL; NOGO; DIFFERENTIATION;

D O I：

10.1016/j.cell.2012.08.020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Neural stem cells (NSCs) expressing GFP were embedded into fibrin matrices containing growth factor cocktails and grafted to sites of severe spinal cord injury. Grafted cells differentiated into multiple cellular phenotypes, including neurons, which extended large numbers of axons over remarkable distances. Extending axons formed abundant synapses with host cells. Axonal growth was partially dependent on mammalian target of rapamycin (mTOR), but not Nogo signaling. Grafted neurons supported formation of electrophysiological relays across sites of complete spinal transection, resulting in functional recovery. Two human stem cell lines (566RSC and HUES7) embedded in growth-factor-containing fibrin exhibited similar growth, and 566RSC cells supported functional recovery. Thus, properties intrinsic to early-stage neurons can overcome the inhibitory milieu of the injured adult spinal cord to mount remarkable axonal growth, resulting in formation of new relay circuits that significantly improve function. These therapeutic properties extend across stem cell sources and species.

引用

页码：1264 / 1273

页数：10

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