important for regulating their fate in vitro. Though stem cells can be conveniently
cultured and expanded on 2D synthetic surfaces, there is a gradual loss in their ability
to self-renew, proliferate, and differentiate into tissue specific cells. Hence, to mimic
the stem cell niches in vitro the minimum requirement is a complex microenvironment including a cell specific surface with topographical distribution of
physical cues to support cell attachment and movement such as matrigel for 3D
organoid culture or flexible surfaces for differentiation into contractile muscle cells
or even complex cell culture approaches like 3D culture, co-culture, dynamic
cultures, physical stimulation, or multiple combinations of the described approaches.
It is clear that the existing tools and strategies for culture are limited and require
improvement for the progress of our understanding about the cell functions on
different surface and strategies for controlled differentiation into clinically relevant
cell types. The key factors regulating cells fate in vitro are medium composition,
surface chemistry, and substrate surface topography. A plethora of reports have been
published describing the standardization of the above mentioned factors to effectively mimic stem cell niches in vitro (Ding et al. 2016; Schuldiner et al. 2000).
Recent development of recombinant proteins have proven to be an improvement
over the currently used mouse embryonic fibroblasts (MEF) supported cultures (e.g.,
M of human PSCs. Being sensitive, PSCs require complex medium with additional
growth factors and ECM to support their self-renewal in vitro compared to other
more differentiated cells. Although several serum free media compositions have
been developed and available commercially in conjunction with modified TCPS
with ECM or cell binding coatings but they still might not be able to maintain the
native state of these PSCs (Theunissen et al. 2014).
References
Akhavan O, Ghaderi E, Akhavan A (2012) Size-dependent genotoxicity of graphene nanoplatelets
in human stem cells. Biomaterials 33:8017–8025
Amy LS, Zhenzhen S, Michael JS, David FBM, Douglas BR, Aaron MB, Erik KF, John AM,
Kenneth PN, Matthew EB, Bruce AB (2014) Effects of the endocrine-disrupting chemical DDT
on self-renewal and differentiation of human Mesenchymal stem cells. Environ Health Perspect
123:42–48
Assoian RK (1997) Anchorage-dependent cell cycle progression. J Cell Biol 136:1–4
Badylak SF, Taylor D, Uygun K (2011) Whole-organ tissue engineering: decellularization and
recellularization of three-dimensional matrix scaffolds. Annu Rev Biomed Eng 13:27–53
Baptista PM, Siddiqui MM, Lozier G, Rodriguez SR, Atala A, Soker S (2011) The use of whole
organ decellularization for the generation of a vascularized liver organoid. Hepatology
53:604–617
Barker N, van de Wetering M, Clevers H (2008) The intestinal stem cell. Genes Dev 22:1856–1864
Batchelder CA, Martinez ML, Tarantal AF (2015) Natural scaffolds for renal differentiation of
human embryonic stem cells for kidney tissue engineering. PLoS One 10:e0143849
Bigot K, de Lange J, Archer G, Clothier R, Bremer S (1999) The relative semi-quantification of
mRNA expression as a useful toxicological endpoint for the identification of Embryotoxic/
Teratogenic substances. Toxicol In Vitro 13:619–623
Blau HM, Cosgrove BD, Ho AT (2015) The central role of muscle stem cells in regenerative failure
with aging. Nat Med 21:854–862
12 Environmental Interaction and Impact on the Life Span of Stem Cells
261
cultured and expanded on 2D synthetic surfaces, there is a gradual loss in their ability
to self-renew, proliferate, and differentiate into tissue specific cells. Hence, to mimic
the stem cell niches in vitro the minimum requirement is a complex microenvironment including a cell specific surface with topographical distribution of
physical cues to support cell attachment and movement such as matrigel for 3D
organoid culture or flexible surfaces for differentiation into contractile muscle cells
or even complex cell culture approaches like 3D culture, co-culture, dynamic
cultures, physical stimulation, or multiple combinations of the described approaches.
It is clear that the existing tools and strategies for culture are limited and require
improvement for the progress of our understanding about the cell functions on
different surface and strategies for controlled differentiation into clinically relevant
cell types. The key factors regulating cells fate in vitro are medium composition,
surface chemistry, and substrate surface topography. A plethora of reports have been
published describing the standardization of the above mentioned factors to effectively mimic stem cell niches in vitro (Ding et al. 2016; Schuldiner et al. 2000).
Recent development of recombinant proteins have proven to be an improvement
over the currently used mouse embryonic fibroblasts (MEF) supported cultures (e.g.,
M of human PSCs. Being sensitive, PSCs require complex medium with additional
growth factors and ECM to support their self-renewal in vitro compared to other
more differentiated cells. Although several serum free media compositions have
been developed and available commercially in conjunction with modified TCPS
with ECM or cell binding coatings but they still might not be able to maintain the
native state of these PSCs (Theunissen et al. 2014).
References
Akhavan O, Ghaderi E, Akhavan A (2012) Size-dependent genotoxicity of graphene nanoplatelets
in human stem cells. Biomaterials 33:8017–8025
Amy LS, Zhenzhen S, Michael JS, David FBM, Douglas BR, Aaron MB, Erik KF, John AM,
Kenneth PN, Matthew EB, Bruce AB (2014) Effects of the endocrine-disrupting chemical DDT
on self-renewal and differentiation of human Mesenchymal stem cells. Environ Health Perspect
123:42–48
Assoian RK (1997) Anchorage-dependent cell cycle progression. J Cell Biol 136:1–4
Badylak SF, Taylor D, Uygun K (2011) Whole-organ tissue engineering: decellularization and
recellularization of three-dimensional matrix scaffolds. Annu Rev Biomed Eng 13:27–53
Baptista PM, Siddiqui MM, Lozier G, Rodriguez SR, Atala A, Soker S (2011) The use of whole
organ decellularization for the generation of a vascularized liver organoid. Hepatology
53:604–617
Barker N, van de Wetering M, Clevers H (2008) The intestinal stem cell. Genes Dev 22:1856–1864
Batchelder CA, Martinez ML, Tarantal AF (2015) Natural scaffolds for renal differentiation of
human embryonic stem cells for kidney tissue engineering. PLoS One 10:e0143849
Bigot K, de Lange J, Archer G, Clothier R, Bremer S (1999) The relative semi-quantification of
mRNA expression as a useful toxicological endpoint for the identification of Embryotoxic/
Teratogenic substances. Toxicol In Vitro 13:619–623
Blau HM, Cosgrove BD, Ho AT (2015) The central role of muscle stem cells in regenerative failure
with aging. Nat Med 21:854–862
12 Environmental Interaction and Impact on the Life Span of Stem Cells
261