Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain

Xiaowei Li; Stephany Y Tzeng; Xiaoyan Liu; Markus Tammia; Yu-Hao Cheng; Andrew Rolfe; Dong Sun; Ning Zhang; Jordan J Green; Xuejun Wen; Hai-Quan Mao

doi:10.1016/j.biomaterials.2016.01.037

Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain

Biomaterials. 2016 Apr:84:157-166. doi: 10.1016/j.biomaterials.2016.01.037. Epub 2016 Jan 20.

Authors

Xiaowei Li¹, Stephany Y Tzeng², Xiaoyan Liu³, Markus Tammia¹, Yu-Hao Cheng⁴, Andrew Rolfe⁵, Dong Sun⁵, Ning Zhang³, Jordan J Green⁶, Xuejun Wen⁷, Hai-Quan Mao⁸

Affiliations

¹ Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA; Department of Materials Science & Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
² Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
³ Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA.
⁴ Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
⁵ Department of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
⁶ Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA; Department of Materials Science & Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁷ Department of Chemical and Life Science Engineering, School of Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA. Electronic address: xwen@vcu.edu.
⁸ Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA; Department of Materials Science & Engineering, Johns Hopkins University, Baltimore, MD 21218, USA. Electronic address: hmao@jhu.edu.

Abstract

Strategies to enhance survival and direct the differentiation of stem cells in vivo following transplantation in tissue repair site are critical to realizing the potential of stem cell-based therapies. Here we demonstrated an effective approach to promote neuronal differentiation and maturation of human fetal tissue-derived neural stem cells (hNSCs) in a brain lesion site of a rat traumatic brain injury model using biodegradable nanoparticle-mediated transfection method to deliver key transcriptional factor neurogenin-2 to hNSCs when transplanted with a tailored hyaluronic acid (HA) hydrogel, generating larger number of more mature neurons engrafted to the host brain tissue than non-transfected cells. The nanoparticle-mediated transcription activation method together with an HA hydrogel delivery matrix provides a translatable approach for stem cell-based regenerative therapy.

Keywords: Nanoparticles; Neurogenin-2; Neuronal differentiation; Transfection; Traumatic brain injury.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Brain / pathology*
Cell Differentiation* / genetics
Cell Survival
Humans
Nanoparticles / chemistry*
Neural Stem Cells / cytology*
Neural Stem Cells / transplantation*
Neurons / cytology*
Polymers / chemical synthesis
Polymers / chemistry
Rats, Nude
Stem Cell Transplantation*
Transcription, Genetic*
Transfection

Substances

Polymers
poly(beta-amino ester)

Abstract

Publication types

MeSH terms

Substances

Grants and funding