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Generation of cortical neurons from human induced-pluripotent stem cells by biodegradable polymeric microspheres loaded with priming factors

Memanishvili, Tamar LU ; Kupatadze, Nino; Tugushi, David; Katsarava, Ramaz; Wattananit, Somsak LU ; Hara, Naomi LU ; Tornero, Daniel LU and Kokaia, Zaal LU (2016) In Biomedical materials (Bristol, England) 11(2).
Abstract

Ischemic stroke is often associated with loss of cortical neurons leading to various neurological deficits. A cell replacement based on stem cell transplantation to repair the damaged brain requires the generation of specific neuronal subtypes. Recently, induced pluripotent stem cells have been used to generate various subtypes of neurons in vitro for transplantation in stroke-damaged brains. However, whether these cells can be primed as neuronal precursors to become cortical projection neurons by means of biomaterials releasing differentiation factors is not known. Here, we report that microspheres of biodegradable poly(ester-amide) composed of adipic acid, L-phenyl-alanine and 1,4-butanediol, loaded with differentiation factors, can... (More)

Ischemic stroke is often associated with loss of cortical neurons leading to various neurological deficits. A cell replacement based on stem cell transplantation to repair the damaged brain requires the generation of specific neuronal subtypes. Recently, induced pluripotent stem cells have been used to generate various subtypes of neurons in vitro for transplantation in stroke-damaged brains. However, whether these cells can be primed as neuronal precursors to become cortical projection neurons by means of biomaterials releasing differentiation factors is not known. Here, we report that microspheres of biodegradable poly(ester-amide) composed of adipic acid, L-phenyl-alanine and 1,4-butanediol, loaded with differentiation factors, can be used to fate human induced pluripotent stem cell-derived long-term expandable neuroepithelial-like stem cells to cortical projection neurons. The three factors, Wnt3A, BMP4 and cyclopamine, were released from loaded microspheres over at least one month following biphasic dynamic time course, promoting cortical differentiation of the cells in vitro. Microspheres did not evoke significant inflammatory response after transplantation into intact rodent brain. Our study shows the potential of biodegradable polymer microspheres to promote neuronal differentiation by continuous release of factors, thereby creating the appropriate microenvironment. This new strategy may improve the efficacy of stem cell-based therapeutic approaches.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biomedical materials (Bristol, England)
volume
11
issue
2
publisher
IOP Publishing Ltd.
external identifiers
  • scopus:84964414022
  • wos:000375523400016
ISSN
1748-6041
DOI
10.1088/1748-6041/11/2/025011
language
English
LU publication?
yes
id
c2998ffc-bc14-475c-a0e8-27d0b98a7b8f
date added to LUP
2016-04-11 14:45:41
date last changed
2017-01-01 08:22:28
@article{c2998ffc-bc14-475c-a0e8-27d0b98a7b8f,
  abstract     = {<p>Ischemic stroke is often associated with loss of cortical neurons leading to various neurological deficits. A cell replacement based on stem cell transplantation to repair the damaged brain requires the generation of specific neuronal subtypes. Recently, induced pluripotent stem cells have been used to generate various subtypes of neurons in vitro for transplantation in stroke-damaged brains. However, whether these cells can be primed as neuronal precursors to become cortical projection neurons by means of biomaterials releasing differentiation factors is not known. Here, we report that microspheres of biodegradable poly(ester-amide) composed of adipic acid, L-phenyl-alanine and 1,4-butanediol, loaded with differentiation factors, can be used to fate human induced pluripotent stem cell-derived long-term expandable neuroepithelial-like stem cells to cortical projection neurons. The three factors, Wnt3A, BMP4 and cyclopamine, were released from loaded microspheres over at least one month following biphasic dynamic time course, promoting cortical differentiation of the cells in vitro. Microspheres did not evoke significant inflammatory response after transplantation into intact rodent brain. Our study shows the potential of biodegradable polymer microspheres to promote neuronal differentiation by continuous release of factors, thereby creating the appropriate microenvironment. This new strategy may improve the efficacy of stem cell-based therapeutic approaches.</p>},
  articleno    = {025011},
  author       = {Memanishvili, Tamar and Kupatadze, Nino and Tugushi, David and Katsarava, Ramaz and Wattananit, Somsak and Hara, Naomi and Tornero, Daniel and Kokaia, Zaal},
  issn         = {1748-6041},
  language     = {eng},
  month        = {03},
  number       = {2},
  publisher    = {IOP Publishing Ltd.},
  series       = {Biomedical materials (Bristol, England)},
  title        = {Generation of cortical neurons from human induced-pluripotent stem cells by biodegradable polymeric microspheres loaded with priming factors},
  url          = {http://dx.doi.org/10.1088/1748-6041/11/2/025011},
  volume       = {11},
  year         = {2016},
}