The Differentiation Stage of Transplanted Stem Cells Modulates Nerve Regeneration

被引：31
作者：
Huang, Ching-Wen [1 ]
Huang, Wen-Chin [1 ,2 ]
Qiu, Xuefeng [1 ,3 ]
da Silva, Flavia Fernandes Ferreira [4 ]
Wang, Aijun [5 ]
Patel, Shyam [1 ]
Nesti, Leon J. [6 ,7 ,8 ]
Poo, Mu-Ming [9 ]
Li, Song [1 ,10 ,11 ]
机构：
[1] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
[2] UC Berkeley UCSF Grad Program Bioengn, Berkeley, CA 94720 USA
[3] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Cardiovasc Surg, Wuhan 430022, Hubei, Peoples R China
[4] Univ Fed Rio de Janeiro, Inst Macromol Prof Eloisa Mano, Rio De Janeiro, Brazil
[5] Univ Calif Davis, Sch Med, Dept Surg, Sacramento, CA 95817 USA
[6] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA
[7] NIAMSD, Clin & Expt Orthopaed, NIH, Bethesda, MD 20892 USA
[8] Walter Reed Natl Mil Med Ctr, Dept Orthopaed Surg, Bethesda, MD 20889 USA
[9] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA
[10] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA
[11] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA
来源：
SCIENTIFIC REPORTS | 2017年 / 7卷
关键词：
NEURAL CREST STEM; DIRECTED DIFFERENTIATION; HUMAN FIBROBLASTS; PLURIPOTENCY; INDUCTION; REPAIR; BDNF; EXPRESSION; NANOFIBERS; GENERATION;
D O I：
10.1038/s41598-017-17043-4
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
In regenerative medicine applications, the differentiation stage of implanted stem cells must be optimized to control cell fate and enhance therapeutic efficacy. We investigated the therapeutic potential of human induced pluripotent stem cell (iPSC)-derived cells at two differentiation stages on peripheral nerve regeneration. Neural crest stem cells (NCSCs) and Schwann cells (NCSC-SCs) derived from iPSCs were used to construct a tissue-engineered nerve conduit that was applied to bridge injured nerves in a rat sciatic nerve transection model. Upon nerve conduit implantation, the NCSC group showed significantly higher electrophysiological recovery at 1 month as well as better gastrocnemius muscle recovery at 5 months than the acellular group, but the NCSC-SC group didn't. Both transplanted NCSCs and NCSC-SCs interacted with newly-growing host axons, while NCSCs showed better survival rate and distribution. The transplanted NCSCs mainly differentiated into Schwann cells with no teratoma formation, and they secreted higher concentrations of brain-derived neurotrophic factor and nerve growth factor than NCSC-SCs. In conclusion, transplantation of iPSC-NCSCs accelerated functional nerve recovery with the involvement of stem cell differentiation and paracrine signaling. This study unravels the in vivo performance of stem cells during tissue regeneration, and provides a rationale of using appropriate stem cells for regenerative medicine.
引用
收藏
页数：12
相关论文
共 53 条
[1]   Neurotrophins BDNF and NT-3 promote axonal re-entry into the distal host spinal cord through Schwann cell-seeded mini-channels [J].
Bamber, NI ;
Li, HY ;
Lu, XB ;
Oudega, M ;
Aebischer, P ;
Xu, XM .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2001, 13 (02) :257-268
[2]   Peripheral nerve regeneration through guidance tubes [J].
Belkas, JS ;
Shoichett, MS ;
Midha, R .
NEUROLOGICAL RESEARCH, 2004, 26 (02) :151-160
[3]   The Role of Rab Proteins in Neuronal Cells and in the Trafficking of Neurotrophin Receptors [J].
Bucci, Cecilia ;
Alifano, Pietro ;
Cogli, Laura .
MEMBRANES, 2014, 4 (04) :642-677
[4]   Inducible Expression of Neurotrophic Factors by Mesenchymal Progenitor Cells Derived from Traumatically Injured Human Muscle [J].
Bulken-Hoover, Jamie D. ;
Jackson, Wesley M. ;
Ji, Youngmi ;
Volger, Jared A. ;
Tuan, Rocky S. ;
Nesti, Leon J. .
MOLECULAR BIOTECHNOLOGY, 2012, 51 (02) :128-136
[5]   Selective activation of NF-kappa B by nerve growth factor through the neurotrophin receptor p75 [J].
Carter, BD ;
Kaltschmidt, C ;
Kaltschmidt, B ;
Offenhauser, N ;
BohmMatthaei, R ;
Baeuerle, PA ;
Barde, YA .
SCIENCE, 1996, 272 (5261) :542-545
[6]   Polycistronic Lentiviral Vector for "Hit and Run'' Reprogramming of Adult Skin Fibroblasts to Induced Pluripotent Stem Cells [J].
Chang, Chia-Wei ;
Lai, Yi-Shin ;
Pawlik, Kevin M. ;
Liu, Kaimao ;
Sun, Chiao-Wang ;
Li, Chao ;
Schoeb, Trenton R. ;
Townes, Tim M. .
STEM CELLS, 2009, 27 (05) :1042-1049
[7]   Neural crest stem and progenitor cells [J].
Crane, Jennifer F. ;
Trainor, Paul A. .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2006, 22 :267-286
[8]   Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2 [J].
Danwei Huangfu ;
Osafune, Kenji ;
Maehr, Rene ;
Guo, Wenjun ;
Eijkelenboom, Astrid ;
Chen, Shuibing ;
Muhlestein, Whitney ;
Melton, Douglas A. .
NATURE BIOTECHNOLOGY, 2008, 26 (11) :1269-1275
[9]   The cellular and molecular basis of peripheral nerve regeneration [J].
Fu, SY ;
Gordon, T .
MOLECULAR NEUROBIOLOGY, 1997, 14 (1-2) :67-116
[10]   EARLY EVENTS IN NEUROTROPHIN SIGNALING VIA TRK AND P75 RECEPTORS [J].
GREENE, LA ;
KAPLAN, DR .
CURRENT OPINION IN NEUROBIOLOGY, 1995, 5 (05) :579-587
123456