12.4.2 Somatic Stem Cell Toxicology
Apart from embryonic stem cell testing, adult stem cells also called somatic stem
cells are utilized in the toxicological studies in vitro. Somatic cells represent the
entire cell pool of an organism excluding the germline cells, while somatic stem cells
(SSCs) are the stem cells located in the adult tissues. In the adult tissue niches, these
SSCs tend to remain quiescent and maintain homeostasis at very low turnover rate.
After tissue injury these cells get triggered to repair damaged tissues through
multiple fold turnover of self-renewal and differentiation (Blau et al. 2015; Engstrom
et al. 2015; Wang et al. 2011). With physiological aging of the body, there is a
progressive disruption in the tissue homeostasis and gradual loss of the ability of
SSCs to repair the damaged differentiated cells (Blau et al. 2015). With reduced
repair potential of the SSCs the environmental pollutants can either cause an
irreversible damage to the tissues which cannot be repaired sufficiently by proliferation and differentiation of SSCs or they can target SSCs directly, causing their
exhaustion resulting their premature aging/or pathological state, including cancer
and eventually death (Wilhelm Engström et al. 2015). Due to the limited differentiation potential of SSCs in comparison to ESCs, they are not utilized in embryotoxicity
studies and teratogenic experiments. However, SSCs have the ability differentiate
and self-renew into somatic stem cells during the periods of infancy and adolescence, thus finding their use in evaluating the detrimental effects of environmental
toxins and pollutants during post-natal development of an adult organism. It was
during 1980 that Robert M. Pratt and his colleagues for the first time demonstrated
the application of SSCs in toxicological testing by using human embryonic palate
derived for prescreening of environmental teratogens (Pratt et al. 1982). Further, Cao
and colleagues first time evaluated the use of hMSCs for in vitro screening of
cytotoxic chemicals for assessing the LD50 (Lethal Dose, 50%) values and in
categorizing the hazardous status of the tested chemicals in accordance to the
globally harmonized system of classification (GHS) (Scanu et al. 2011). Findings
from these studies demonstrated that hMSCs could serve as precise model for
mimicking the in vivo conditions in comparison to the previously established tests
such as Normal Human Keratinocyte/Neutral Red Uptake methods and validated
3T3 cell test. Thus, primary tissue-derived or PSC-derived (ESC or iPSC) SSCs can
be utilized in vitro for assessing the harmful effects of pollutants on the development
of infants and adolescents into adults. SSC-based injury or disease models can also
be used in specific applications where the toxic effects of chemical during tissue
repair following injury or degenerative diseases are to be assessed. They can also be
used in determining the effects of pollutants on stem cell aging and exhaustion.
Akhavan and group (Akhavan et al. 2012) evaluated the toxicity of graphene
based materials on SSCs. They demonstrated that reduced graphene oxide
nanoplatelets at low concentrations (0.1 mg/mL) exerted genotoxic effects on
hMSCs as a result of chromosomal aberrations and DNA fragmentation. Later,
Strong and colleagues studied the toxic effect of endocrine-disrupting chemical
dichlorodiphenyltrichloroethane (DDT) on SSCs. The groups treated hMSCs with
DDT and revealed significant modifications in the stem cell properties including
12 Environmental Interaction and Impact on the Life Span of Stem Cells
257
Apart from embryonic stem cell testing, adult stem cells also called somatic stem
cells are utilized in the toxicological studies in vitro. Somatic cells represent the
entire cell pool of an organism excluding the germline cells, while somatic stem cells
(SSCs) are the stem cells located in the adult tissues. In the adult tissue niches, these
SSCs tend to remain quiescent and maintain homeostasis at very low turnover rate.
After tissue injury these cells get triggered to repair damaged tissues through
multiple fold turnover of self-renewal and differentiation (Blau et al. 2015; Engstrom
et al. 2015; Wang et al. 2011). With physiological aging of the body, there is a
progressive disruption in the tissue homeostasis and gradual loss of the ability of
SSCs to repair the damaged differentiated cells (Blau et al. 2015). With reduced
repair potential of the SSCs the environmental pollutants can either cause an
irreversible damage to the tissues which cannot be repaired sufficiently by proliferation and differentiation of SSCs or they can target SSCs directly, causing their
exhaustion resulting their premature aging/or pathological state, including cancer
and eventually death (Wilhelm Engström et al. 2015). Due to the limited differentiation potential of SSCs in comparison to ESCs, they are not utilized in embryotoxicity
studies and teratogenic experiments. However, SSCs have the ability differentiate
and self-renew into somatic stem cells during the periods of infancy and adolescence, thus finding their use in evaluating the detrimental effects of environmental
toxins and pollutants during post-natal development of an adult organism. It was
during 1980 that Robert M. Pratt and his colleagues for the first time demonstrated
the application of SSCs in toxicological testing by using human embryonic palate
derived for prescreening of environmental teratogens (Pratt et al. 1982). Further, Cao
and colleagues first time evaluated the use of hMSCs for in vitro screening of
cytotoxic chemicals for assessing the LD50 (Lethal Dose, 50%) values and in
categorizing the hazardous status of the tested chemicals in accordance to the
globally harmonized system of classification (GHS) (Scanu et al. 2011). Findings
from these studies demonstrated that hMSCs could serve as precise model for
mimicking the in vivo conditions in comparison to the previously established tests
such as Normal Human Keratinocyte/Neutral Red Uptake methods and validated
3T3 cell test. Thus, primary tissue-derived or PSC-derived (ESC or iPSC) SSCs can
be utilized in vitro for assessing the harmful effects of pollutants on the development
of infants and adolescents into adults. SSC-based injury or disease models can also
be used in specific applications where the toxic effects of chemical during tissue
repair following injury or degenerative diseases are to be assessed. They can also be
used in determining the effects of pollutants on stem cell aging and exhaustion.
Akhavan and group (Akhavan et al. 2012) evaluated the toxicity of graphene
based materials on SSCs. They demonstrated that reduced graphene oxide
nanoplatelets at low concentrations (0.1 mg/mL) exerted genotoxic effects on
hMSCs as a result of chromosomal aberrations and DNA fragmentation. Later,
Strong and colleagues studied the toxic effect of endocrine-disrupting chemical
dichlorodiphenyltrichloroethane (DDT) on SSCs. The groups treated hMSCs with
DDT and revealed significant modifications in the stem cell properties including
12 Environmental Interaction and Impact on the Life Span of Stem Cells
257