Award Abstract # 0748340
CAREER: Controlling Neural Stem Cell State and Fate by Functional Nanofiber Cues

NSF Org: DMR
Division Of Materials Research
Recipient: THE JOHNS HOPKINS UNIVERSITY
Initial Amendment Date: February 11, 2008
Latest Amendment Date: January 17, 2012
Award Number: 0748340
Award Instrument: Continuing Grant
Program Manager: Joseph A. Akkara
DMR
 Division Of Materials Research
MPS
 Directorate for Mathematical and Physical Sciences
Start Date: February 1, 2008
End Date: January 31, 2013 (Estimated)
Total Intended Award Amount: $500,000.00
Total Awarded Amount to Date: $500,000.00
Funds Obligated to Date: FY 2008 = $100,000.00
FY 2009 = $100,000.00

FY 2010 = $100,000.00

FY 2011 = $100,000.00

FY 2012 = $100,000.00
History of Investigator:
  • Hai-Quan Mao (Principal Investigator)
    hmao@jhu.edu
Recipient Sponsored Research Office: Johns Hopkins University
3400 N CHARLES ST
BALTIMORE
MD  US  21218-2608
(443)997-1898
Sponsor Congressional District: 07
Primary Place of Performance: Johns Hopkins University
3400 N CHARLES ST
BALTIMORE
MD  US  21218-2608
Primary Place of Performance
Congressional District:
07
Unique Entity Identifier (UEI): FTMTDMBR29C7
Parent UEI: GS4PNKTRNKL3
NSF Program(s): BIOMATERIALS PROGRAM
Primary Program Source: 01000809DB NSF RESEARCH & RELATED ACTIVIT
01000910DB NSF RESEARCH & RELATED ACTIVIT

01001011DB NSF RESEARCH & RELATED ACTIVIT

01001112DB NSF RESEARCH & RELATED ACTIVIT

01001213DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 1045, 7573, 9161, AMPP
Program Element Code(s): 762300
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.049

ABSTRACT

This Career award by the Biomaterials program in the Division of Materials Research to Johns Hopkins University aims to test the hypothesis that the presentation of topographical and surface tethered biochemical cues by nanofibers can potentiate neural stem cell (NSC) adhesion, contact guidance, and growth factor signaling, and thereby regulate NSC adhesion, proliferation, differentiation, and migration. To achieve this goal, polycaprolactone nanofibers are prepared by electrospinning and they are surface-conjugated with adhesion molecules (laminin and fibronectin) and fibroblast growth factor-2 with controlled concentration gradients and distributions. This platform will be used to systematically analyze the effect of nanofiber-presented topographical and biochemical cues, either independently or in combination, on NSC adhesion, proliferation, differentiation and migration. These studies are expected to demonstrate the ability to manipulate NSC behavior through the synergistic integration of the various cues. Neural stem cells offer tremendous potential for treating degenerative diseases and traumatic injuries of the central nervous system. Their clinical application, however, faces the challenges of insufficient cell number and poor control over NSC state and fate, problems due partly to our limited understanding of signaling regulation of NSCs by the extra cellular matrix microenvironment cues.

Scientific impact of the proposal is in the field of regenerative medicine by providing improvement in health care and quality of life. The education and outreach components of the proposal include a number of novel ideas and applications, and are well integrated with the projects research plans. Active participation with Women in Science and Engineering program to attract high-school female students to science and bio/engineering interface, association with clinical partners, and introduction of undergraduates to patenting and intellectual property development are other parts of this project. In addition, a new bioengineering course will be developed at the University.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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Christopherson, GT; Song, H; Mao, HQ "The influence of fiber diameter of electrospun substrates on neural stem cell differentiation and proliferation" BIOMATERIALS , v.30 , 2009 , p.556 View record at Web of Science 10.1016/j.biomaterials.2008.10.00
Fischer SE, Mi L, Mao HQ, Harden JL. "Biofunctional coatings via targeted covalent cross-linking of associating triblock proteins" Biomacromolecules , v.10 , 2009 , p.2408
Krick, K; Tammia, M; Martin, R; Hoke, A; Mao, HQ "Signaling cue presentation and cell delivery to promote nerve regeneration" CURRENT OPINION IN BIOTECHNOLOGY , v.22 , 2011 , p.741 View record at Web of Science 10.1016/j.copbio.2011.04.00
Lim SH, and Mao HQ. "Electrospun scaffolds for stem cell engineering" Adv. Drug Deliv. Rev. , v.61 , 2009 , p.1084
Lim SH, Liu XY, Song H, Yarema KJ, Mao HQ. "The effect of nanofiber-guided cell alignment on the preferential differentiation of neural stem cells" Biomaterials , v.31 , 2010 , p.9031 10.1016/j.biomaterials.2010.08.021
Mahairaki, V; Lim, SH; Christopherson, GT; Xu, LY; Nasonkin, I; Yu, C; Mao, HQ; Koliatsos, VE "Nanofiber Matrices Promote the Neuronal Differentiation of Human Embryonic Stem Cell-Derived Neural Precursors In Vitro" TISSUE ENGINEERING PART A , v.17 , 2011 , p.855 View record at Web of Science 10.1089/ten.tea.2010.037
Ren YJ, Zhang S, Mi R, Liu Q, Zeng X, Rao M, Hoke A, Mao HQ "Enhanced differentiation of human neural crest stem cells towards the Schwann cell lineage by aligned electrospun fiber matrix" Acta Biomaterialia , v.9 , 2013 , p.1-10 http://dx.doi.org/10.1016/j.actbio.2013.04.034
Wall, BD; Diegelmann, SR; Zhang, SM; Dawidczyk, TJ; Wilson, WL; Katz, HE; Mao, HQ; Tovar, JD "Aligned Macroscopic Domains of Optoelectronic Nanostructures Prepared via Shear-Flow Assembly of Peptide Hydrogels" ADVANCED MATERIALS , v.23 , 2011 , p.5009 View record at Web of Science 10.1002/adma.20110296

PROJECT OUTCOMES REPORT

Disclaimer

This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.

The goal of the research project is to understand the local regulation of the proliferation and differentiation of neural stem cells by nanofiber-presented topographical and biochemical cues.  Major research outcomes include (1) development of a functional electrospun fiber matrix platform with precise control over their diameters, alignment, and surface functionalities tailored for adult neural stem cells (NSCs) and ESC-derived NSCs and neural crest stem cells (NCSCs), (2) demonstration of nanofiber diameter and alignment as important parameters influencing NSC-differentiation, and neural crest stem cell differentiation, (3) understanding the role of nanofiber cue in regulating beta-catenin level and influencing the fate specification and differentiation, (4) the synergistic effect between the topographical cue (nanofiber matrix) and the biochemical cue (insulin like growth factor 1, IGF-1, and noggin) in promoting Schwann cell differentiation, (5) identification of optimal nanofiber-culture protocols for oligodendrocyte and Schwann cell differentiation, (6) development of degradable nanofiber matrix for ex vivo neural stem cell differentiation culture, and (7) demonstration of the aligned nanofiber matrix as a guidance cue for peripheral nerve regeneration.  Major education and outreach achievements include (1) development of the “Biomaterials Lab” curriculum and a teaching lab for the course, which has enrolled more than 56 students over the past five years; (2) promotion of diversity and participation of undergraduate students (total of 22) and high school students (total of 9) from underrepresented minority groups (total of 14 female, Hispanic, and African American), (3) enhancing undergraduate student research opportunities by serving as the co-PI of NSF Johns Hopkins University REU-Site Program in Nanotechnology for Biology and Medicine, (4) mentoring several student design teams for bioengineering innovation—two of the teams won national awards and one team won the Coulter Development Award, and (5) creating opportunities for students and postdoctoral fellows to work with biotech corporate partners—this experience provided a valuable and unique training to students on engineering at work in biotech industry.  Four primary papers (leading role), six secondary papers (minor role) and three review papers have been published and three more in preparation.  Four graduate students and two postdoctoral fellows have been partially supported by this grant. 


Last Modified: 05/02/2013
Modified by: Hai-Quan Mao

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