ADD references to the microcarrier section
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@ -1799,6 +1799,147 @@ CONCLUSIONS: We developed a simplified, semi-closed system for the initial selec
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publisher = {Informa {UK} Limited},
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publisher = {Informa {UK} Limited},
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}
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}
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@Article{WEZEL1967,
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author = {A. L. VAN WEZEL},
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journal = {Nature},
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title = {Growth of Cell-strains and Primary Cells on Micro-carriers in Homogeneous Culture},
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year = {1967},
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month = {oct},
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number = {5110},
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pages = {64--65},
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volume = {216},
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doi = {10.1038/216064a0},
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publisher = {Springer Science and Business Media {LLC}},
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}
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@Article{Derakhti2019,
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author = {Sorour Derakhti and Seyed Hamid Safiabadi-Tali and Ghassem Amoabediny and Mojgan Sheikhpour},
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journal = {Materials Science and Engineering: C},
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title = {Attachment and detachment strategies in microcarrier-based cell culture technology: A comprehensive review},
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year = {2019},
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month = {oct},
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pages = {109782},
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volume = {103},
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doi = {10.1016/j.msec.2019.109782},
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publisher = {Elsevier {BV}},
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}
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@Article{Chen2013,
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author = {Allen Kuan-Liang Chen and Shaul Reuveny and Steve Kah Weng Oh},
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journal = {Biotechnology Advances},
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title = {Application of human mesenchymal and pluripotent stem cell microcarrier cultures in cellular therapy: Achievements and future direction},
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year = {2013},
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month = {nov},
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number = {7},
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pages = {1032--1046},
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volume = {31},
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doi = {10.1016/j.biotechadv.2013.03.006},
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publisher = {Elsevier {BV}},
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}
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@Article{Xiao1999,
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author = {Chengzu Xiao and Zicai Huang and Wengqing Li and Xianwen Hu and Wenlu Qu and Lihua Gao and Gaoyan Liu},
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journal = {Cytotechnology},
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title = {{High} density and scale-up cultivation of recombinant {CHO} cell line and hybridomas with porous microcarrier {Cytopore}},
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year = {1999},
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number = {1/3},
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pages = {143--147},
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volume = {30},
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doi = {10.1023/a:1008038609967},
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publisher = {Springer Science and Business Media {LLC}},
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}
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@Article{Kim2011,
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author = {Beum Jun Kim and Ti Zhao and Lincoln Young and Peng Zhou and Michael L. Shuler},
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journal = {Biotechnology and Bioengineering},
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title = {Batch, fed-batch, and microcarrier cultures with {CHO} cell lines in a pressure-cycle driven miniaturized bioreactor},
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year = {2011},
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month = {oct},
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number = {1},
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pages = {137--145},
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volume = {109},
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doi = {10.1002/bit.23289},
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publisher = {Wiley},
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}
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@Article{Zhang2016,
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author = {Zhanpeng Zhang and Thomas W Eyster and Peter X Ma},
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journal = {Nanomedicine},
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title = {Nanostructured injectable cell microcarriers for tissue regeneration},
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year = {2016},
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month = {jun},
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number = {12},
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pages = {1611--1628},
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volume = {11},
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doi = {10.2217/nnm-2016-0083},
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publisher = {Future Medicine Ltd},
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}
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@Article{Saltz2016,
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author = {Adam Saltz and Umadevi Kandalam},
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journal = {Journal of Biomedical Materials Research Part A},
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title = {Mesenchymal stem cells and alginate microcarriers for craniofacial bone tissue engineering: A review},
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year = {2016},
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month = {jan},
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number = {5},
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pages = {1276--1284},
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volume = {104},
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doi = {10.1002/jbm.a.35647},
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publisher = {Wiley},
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}
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@Article{Park2013,
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author = {Jeong-Hui Park and Rom{\'{a}}n A. P{\'{e}}rez and Guang-Zhen Jin and Seung-Jun Choi and Hae-Won Kim and Ivan B. Wall},
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journal = {Tissue Engineering Part B: Reviews},
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title = {Microcarriers Designed for Cell Culture and Tissue Engineering of Bone},
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year = {2013},
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month = {apr},
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number = {2},
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pages = {172--190},
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volume = {19},
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doi = {10.1089/ten.teb.2012.0432},
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publisher = {Mary Ann Liebert Inc},
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}
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@Article{Malda2006,
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author = {Jos Malda and Carmelita G. Frondoza},
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journal = {Trends in Biotechnology},
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title = {Microcarriers in the engineering of cartilage and bone},
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year = {2006},
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month = {jul},
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number = {7},
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pages = {299--304},
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volume = {24},
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doi = {10.1016/j.tibtech.2006.04.009},
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publisher = {Elsevier {BV}},
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}
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@Article{Schop2010,
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author = {D. Schop and R. van Dijkhuizen-Radersma and E. Borgart and F. W. Janssen and H. Rozemuller and H-J. Prins and J. D. de Bruijn},
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journal = {Journal of Tissue Engineering and Regenerative Medicine},
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title = {Expansion of human mesenchymal stromal cells on microcarriers: growth and metabolism},
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year = {2010},
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month = {feb},
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number = {2},
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pages = {131--140},
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volume = {4},
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doi = {10.1002/term.224},
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publisher = {Wiley},
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}
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@Article{Rafiq2016,
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author = {Qasim A. Rafiq and Karen Coopman and Alvin W. Nienow and Christopher J. Hewitt},
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journal = {Biotechnology Journal},
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title = {Systematic microcarrier screening and agitated culture conditions improves human mesenchymal stem cell yield in bioreactors},
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year = {2016},
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month = {feb},
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number = {4},
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pages = {473--486},
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volume = {11},
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doi = {10.1002/biot.201400862},
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publisher = {Wiley},
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}
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@Comment{jabref-meta: databaseType:bibtex;}
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@Comment{jabref-meta: databaseType:bibtex;}
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@Comment{jabref-meta: grouping:
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@Comment{jabref-meta: grouping:
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@ -579,40 +579,39 @@ present our final conclusions in Chapter~\ref{conclusions}.
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Microcarriers have historically been used to grow a number of adherent cell
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Microcarriers have historically been used to grow a number of adherent cell
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types for a variety of applications. They were introduced in 1967 as a means to
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types for a variety of applications. They were introduced in 1967 as a means to
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grow adherent cells `in suspension', effectively turning a 2D flask system into
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grow adherent cells `in suspension', effectively turning a 2D flask system into
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a 3D culture system (https://www.nature.com/articles/216064a0.pdf).
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a 3D culture system\cite{WEZEL1967}. Microcarriers are generally spherical and
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Microcarriers are generally spherical and are several hundred \si{\um} in
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are several hundred \si{\um} in diameter, which means they collectively have a
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diameter, which means they collectively have a much higher surface area than a
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much higher surface area than a traditional flask when matched for volume.
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traditional flask when matched for volume. Consequently, this means that
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Consequently, this means that microcarrier-based cultures can operate with much
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microcarrier-based cultures can operate with much lower footprints than
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lower footprints than flask-like systems. Microcarriers also allow cell culture
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flask-like systems. Microcarriers also allow cell culture to operate more like a
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to operate more like a traditional chemical engineering process, wherein a
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traditional chemical engineering process, wherein a stirred tank bioreactor may
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stirred tank bioreactor may be employed to enhance oxygen transfer, maintain pH,
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be employed to enhance oxygen transfer, maintain pH, and continuously supply
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and continuously supply nutrients\cite{Derakhti2019}.
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nutrients ().
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A variety of microcarriers have been designed, primarily differing in their
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A variety of microcarriers have been designed, primarily differing in their
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choice of material and macroporous structure. Key concerns have been cell
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choice of material and macroporous structure. Key concerns have been cell
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attachment at the beginning of culture and cell detachment at the harvesting
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attachment at the beginning of culture and cell detachment at the harvesting
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step; these have largely driven the nature of the material and structures
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step; these have largely driven the nature of the material and structures
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employed. Many microcarriers simply use polystyrene (the material used for
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employed\cite{Derakhti2019}. Many microcarriers simply use polystyrene (the
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tissue culture flasks and dishes in general) with no modification (SoloHill
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material used for tissue culture flasks and dishes in general) with no
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Plastic, Nunc Biosilon), with a cationic surface charge (SoloHill Hillex) or
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modification (SoloHill Plastic, Nunc Biosilon), with a cationic surface charge
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coated with an \gls{ecm} protein such as collagen (SoloHill Fact III). Other
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(SoloHill Hillex) or coated with an \gls{ecm} protein such as collagen (SoloHill
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base materials have been used such as dextran (GE Healthcare Cytodex), cellulose
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Fact III). Other base materials have been used such as dextran (GE Healthcare
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(GE Healthcare Cytopore), and glass (Sigma Aldrich G2767), all with none or
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Cytodex), cellulose (GE Healthcare Cytopore), and glass (Sigma Aldrich G2767),
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similar surface modifications. Additionally, some microcarriers such as
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all with none or similar surface modifications. Additionally, some microcarriers
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\gls{cus} and \gls{cug} are composed entirely out of protein (in these cases,
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such as \gls{cus} and \gls{cug} are composed entirely out of protein (in these
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porcine collagen) which also allows the microcarriers to be enzymatically
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cases, porcine collagen) which also allows the microcarriers to be enzymatically
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degraded. In the case of non-protein materials, cells may still be detached
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degraded. In the case of non-protein materials, cells may still be detached
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using enzymes but these require similar methods to those currently used in
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using enzymes but these require similar methods to those currently used in
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flasks such as trypsin which target the cellular \gls{ecm} directly. Since
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flasks such as trypsin which target the cellular \gls{ecm} directly. Since
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trypsin and related enzymes tends to be harsh on cells, an advantage of using
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trypsin and related enzymes tends to be harsh on cells, an advantage of using
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entirely protein-based microcarriers is that they can be degraded using a much
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entirely protein-based microcarriers is that they can be degraded using a much
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safer enzyme such as collagenase, at the cost of being more expensive and also
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safer enzyme such as collagenase, at the cost of being more expensive and also
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being harder to make \gls{gmp}-compliant. Going one step further, some
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being harder to make \gls{gmp}-compliant\cite{Derakhti2019}. Going one step
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microcarriers are composed of a naturally degrading scaffold such as alginate,
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further, some microcarriers are composed of a naturally degrading scaffold such
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which do not need an enzyme for degradation but are limited in that the
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as alginate, which do not need an enzyme for degradation but are limited in that
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degradation process is less controllable. Finally, microcarriers can differ in
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the degradation process is less controllable. Finally, microcarriers can differ
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their overall structure. \gls{cug} and \gls{cus} microcarriers as well as the
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in their overall structure. \gls{cug} and \gls{cus} microcarriers as well as the
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Cytopore microcarriers are macroporous, meaning they have a porous network in
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Cytopore microcarriers are macroporous, meaning they have a porous network in
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which cells can attach throughout their interior. This drastically increases the
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which cells can attach throughout their interior. This drastically increases the
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effective surface area and consequently the number of cells which may be grown
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effective surface area and consequently the number of cells which may be grown
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@ -620,18 +619,16 @@ per unit volume. Other microcarriers are microporous (eg only to small
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molecules) or not porous at all (eg polystyrene) in which case the cells can
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molecules) or not porous at all (eg polystyrene) in which case the cells can
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only grow on the surface.
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only grow on the surface.
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% https://www.sciencedirect.com/science/article/pii/S0734975013000657
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% https://link.springer.com/article/10.1023/A:1008038609967
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% https://onlinelibrary.wiley.com/doi/full/10.1002/bit.23289
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Microcarriers have seen the most use in growing \gls{cho} cells and hybridomas
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Microcarriers have seen the most use in growing \gls{cho} cells and hybridomas
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in the case of protein manufacturing (eg \gls{igg} production) as well as
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in the case of protein manufacturing (eg \gls{igg} production)\cite{Xiao1999,
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pluripotent stem cells and mesenchymal stromal cells more recently in the case
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Kim2011} as well as pluripotent stem cells and mesenchymal stromal cells more
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of cell manufacturing\cite{Heathman2015, Sart2011}. Interestingly, some groups
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recently in the case of cell manufacturing\cite{Heathman2015, Sart2011,
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have even explored using biodegradable microcarriers \invivo{} as a delivery
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Chen2013, Schop2010, Rafiq2016}. Interestingly, some groups have even explored
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vehicle for stem cell therapies in the context of regenerative medicine.
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using biodegradable microcarriers \invivo{} as a delivery vehicle for stem cell
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However, the characteristic shared by all the cell types in this application is
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therapies in the context of regenerative medicine\cite{Zhang2016, Saltz2016,
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the fact that they are adherent. In this work, we explore the use of
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Park2013, Malda2006}. However, the characteristic shared by all the cell types
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microcarrier for T cells, which are naturally non-adherent.
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in this application is the fact that they are adherent. In this work, we explore
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the use of microcarrier for T cells, which are naturally non-adherent.
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\subsection{overview of T cells in immunotherapies}
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\subsection{overview of T cells in immunotherapies}
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