The concept of cellular reprogramming was developed to generate induced neural precursor cells (iNPCs)/dopaminergic (iDA) neurons using diverse approaches. Here, we investigated the effects of various nanoscale scaffolds (fiber, dot, and line) on iNPC/iDA differentiation by direct reprogramming. The generation and maturation of iDA neurons (microtubule-associated protein 2-positive and tyrosine hydroxylase-positive) and iNPCs (NESTIN-positive and SOX2-positive) increased on fiber and dot scaffolds as compared to that of the flat (control) scaffold. This study demonstrates that nanotopographical environments are suitable for direct differentiation methods and may improve the differentiation efficiency.
1. Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M. Direct conversion of fibroblasts to functional neurons by defined factors. Nature 2010;463:1035- 1041
2. Kim J, Efe JA, Zhu S, Talantova M, Yuan X, Wang S, Lipton SA, Zhang K, Ding S. Direct reprogramming of mouse fibroblasts to neural progenitors. Proc Natl Acad Sci U S A 2011;108:7838-7843
4. Lim MS, Chang MY, Kim SM, Yi SH, Suh-Kim H, Jung SJ, Kim MJ, Kim JH, Lee YS, Lee SY, Kim DW, Lee SH, Park CH. Generation of dopamine neurons from rodent fibroblasts through the expandable neural precursor cell stage. J Biol Chem 2015;290:17401-17414
5. Lim MS, Lee SY, Park CH. FGF8 is essential for functionality of induced neural precursor cell-derived dopaminergic neurons. Int J Stem Cells 2015;8:228-234
6. Kim SM, Kim JW, Kwak TH, Park SW, Kim KP, Park H, Lim KT, Kang K, Kim J, Yang JH, Han H, Lee I, Hyun JK, Bae YM, Schöler HR, Lee HT, Han DW. Generation of integration-free induced neural stem cells from mouse fibroblasts. J Biol Chem 2016;291:14199-14212
7. Kim J, Kim KP, Lim KT, Lee SC, Yoon J, Song G, Hwang SI, Schöler HR, Cantz T, Han DW. Generation of integration-free induced hepatocyte-like cells from mouse fibroblasts. Sci Rep 2015;5:15706
8. Li X, Zuo X, Jing J, Ma Y, Wang J, Liu D, Zhu J, Du X, Xiong L, Du Y, Xu J, Xiao X, Wang J, Chai Z, Zhao Y, Deng H. Small-molecule-driven direct reprogramming of mouse fibroblasts into functional neurons. Cell Stem Cell 2015;17:195-203
9. Zheng J, Choi KA, Kang PJ, Hyeon S, Kwon S, Moon JH, Hwang I, Kim YI, Kim YS, Yoon BS, Park G, Lee J, Hong S, You S. A combination of small molecules directly reprograms mouse fibroblasts into neural stem cells. Biochem Biophys Res Commun 2016;476:42-48
10. Lim MS, Kim SM, Lee EH, Park CH. Efficient induction of neural precursor cells from fibroblasts using stromal cell-derived inducing activity. Tissue Eng Regen Med 2016;13:554-559
12. McMurray RJ, Gadegaard N, Tsimbouri PM, Burgess KV, McNamara LE, Tare R, Murawski K, Kingham E, Oreffo RO, Dalby MJ. Nanoscale surfaces for the long-term maintenance of mesenchymal stem cell phenotype and multipotency. Nat Mater 2011;10:637-644
13. Kulangara K, Adler AF, Wang H, Chellappan M, Hammett E, Yasuda R, Leong KW. The effect of substrate topography on direct reprogramming of fibroblasts to induced neurons. Biomaterials 2014;35:5327-5336
14. Yoo J, Noh M, Kim H, Jeon NL, Kim BS, Kim J. Nanogrooved substrate promotes direct lineage reprogramming of fibroblasts to functional induced dopaminergic neurons. Biomaterials 2015;45:36-45
17. Anderson JM, Kushwaha M, Tambralli A, Bellis SL, Camata RP, Jun HW. Osteogenic differentiation of human mesenchymal stem cells directed by extracellular matrix-mimicking ligands in a biomimetic self-assembled peptide amphiphile nanomatrix. Biomacromolecules 2009;10: 2935-2944
19. O'Cearbhaill ED, Punchard MA, Murphy M, Barry FP, McHugh PE, Barron V. Response of mesenchymal stem cells to the biomechanical environment of the endothelium on a flexible tubular silicone substrate. Biomaterials 2008; 29:1610-1619
22. Park J, Cho CH, Parashurama N, Li Y, Berthiaume F, Toner M, Tilles AW, Yarmush ML. Microfabrication-based modulation of embryonic stem cell differentiation. Lab Chip 2007;7:1018-1028
23. Dalby MJ, Gadegaard N, Tare R, Andar A, Riehle MO, Herzyk P, Wilkinson CD, Oreffo RO. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat Mater 2007;6:997-1003
24. Oh S, Brammer KS, Li YS, Teng D, Engler AJ, Chien S, Jin S. Stem cell fate dictated solely by altered nanotube dimension. Proc Natl Acad Sci U S A 2009;106:2130-2135
25. Lee MR, Kwon KW, Jung H, Kim HN, Suh KY, Kim K, Kim KS. Direct differentiation of human embryonic stem cells into selective neurons on nanoscale ridge/groove pattern arrays. Biomaterials 2010;31:4360-4366
27. Li H, Wen F, Chen H, Pal M, Lai Y, Zhao AZ, Tan LP. Micropatterning extracellular matrix proteins on electrospun fibrous substrate promote human mesenchymal stem cell differentiation toward neurogenic lineage. ACS Appl Mater Interfaces 2016;8:563-573
28. You MH, Kwak MK, Kim DH, Kim K, Levchenko A, Kim DY, Suh KY. Synergistically enhanced osteogenic differentiation of human mesenchymal stem cells by culture on nanostructured surfaces with induction media. Biomacromolecules 2010;11:1856-1862
29. Roberts JN, Sahoo JK, McNamara LE, Burgess KV, Yang J, Alakpa EV, Anderson HJ, Hay J, Turner LA, Yarwood SJ, Zelzer M, Oreffo RO, Ulijn RV, Dalby MJ. Dynamic surfaces for the study of mesenchymal stem cell growth through adhesion regulation. ACS Nano 2016;10:6667-6679
30. Ventre M, Netti PA. Engineering cell instructive materials to control cell fate and functions through material cues and surface patterning. ACS Appl Mater Interfaces 2016;8: 14896-14908
more
references