1 Histopathologist, AB Diagnostics, New Delhi, India
Corresponding author details:
Copyright: © 2019 Anubha B. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 international License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Embryonic stem cells; Embryonal carcinoma cellS; Induced pleuripotent stem cells;
Adult stem cells
Emergence of cancer is contemplated as a genetic phenomenon wherein genetic
evolution of malignant cells modifies the progression of individual tumour. Genetic
mutations are a conjectural phenomenon and unsynchronized mutational configurations
can appear. Accumulations of cancer cells articulate a dynamic environment comprised of
multiple, heterogeneous tumour cell territories and distinctive molecular signatures
pertaining to diverse malignancies with cogent genomic mutations. Fundamental biological
processes as designated with committed cancer stem cell lineage, definitive genetic
evolution, signalling cascades with explicit oncogenes, modes of neo vascularization and
interactions pertaining to tumour cell microenvironment are analysed [1,2]. Stem cell as a
terminology was initially adopted by a German biologist “Ernst Haeckel” in 1868. Currently,
five principal categories of stem cells are cogitated for therapeutic purposes and defined as
embryonic stem cells (ESCs), embryonal carcinoma cells (ECCs), induced pleuripotent stem
cells (iPSCs), germinal stem cells and adult stem cells (ASCs). Morphological enunciation of
a stem cell is designated as a spherical cell with minimal cytoplasm and an enlarged nucleus
with elevated nucleus/ cytoplasmic ratio. Several lineage specific biomarkers are available
to distinguish the stem cell, however, alkaline phosphatase is discernible in a majority of
stem cell categories [1,2]. Embryonic stem cells (ESC) are particular cells which are
engendered from inmost cellular aggregates of blastocyst stage of embryonal development.
Embryonic stem cells are self- replicating cells and demonstrate a pleuripotent capacity
with an ability to differentiate into three pertinent germ cell layers. The diverse cell types
can be adopted into contemporary methodologies of stem cell therapies. Embryonic stem
cells can be supplanted with induced pleuripotent stem cells (iPSCs) which are essentially
reprogrammed cells engendered from adult somatic cells or cutaneous fibroblasts. Induced
pleuripotent stem cells recapitulate embryonic stem cells and are devoid of immunogenic
features or ethical considerations cogent for stem cell transplantation [2,3]. Foetal stem
cells can be harvested from placenta, amniotic membranes, amniotic fluid or foetal tissues
and display an enhanced capability of maturation and differentiation, in contrast to stem
cells obtained from adult tissues. Somatic stem cells (SSCs) or adult stem cells (ASCs) can
further differentiate into neural stem cells (NSCs), mesenchymal stem cells (MSCs),
haematopoietic stem cells (HSCs), endothelial progenitor stem cells (EPCs) and adjunctive
cells. Adult stem cells are beneficial for adequate regeneration and replacement of soft
tissues and are considered a preferential therapeutic modality for the discipline of
regenerative medicine [2,3] [Table 1]. Cancer stem cells are tumour propagating cells which
delineate varying characteristics including self-renewal. Cancer stem cells (CSCs) contribute
as a miniature proportion of malignant tumours. Cancer stem cells can enunciate potential
and impending differentiation towards heterogeneous tumour cell colonies and account for
tumour reoccurrences and inferior response to therapy with eventual evolution of
therapeutic resistance. Cancer stem cells are situated in and harvested from diverse tumour
tissues as associated with carcinoma breast, colorectal carcinomaor carcinoma pancreas.
Aforesaid stem cells demonstrate distinct biophysical properties and response to diverse
treatment methodologies, in contrast to accompanying terminally differentiated cancer
(TDC) cells [3,4]. Avant-Garde Approach Cancer stem cells commonly depict an immortal
phenotype and can initiate a tumour reoccurrence. Categorical varieties of cancer and
relapses can be engendered following administered chemotherapy and/or radiotherapy.
Apart from self renewal and differentiation, stem cells demonstrate unique attributes such
as migration towards cancer cells, anti-tumour activity, secretion of bioactive molecules and
immune suppression. Aforesaid properties promote the isolation and targeting of tumour
cells and circumvent impediments to effective and contemporary gene therapy [4,5]. Cancer
cells originating from progenitor cells or preliminary stem cells can induce a precipitous
metastasis and tumour cell deposits with extensive genetic heterogeneity. Metastasis generated from late- appearing stages of stem cells are homogenous
and exhibit limited potential for tumour dissemination. Tumour
heterogeneity and a penchant for distant metastasis is contingent to
differentiation and/ or dedifferentiation of cancer stem cells. A
significantly advantageous therapeutic prototype can be obtained
with the process of targeting cancer stem cells rather than terminally
differentiated stem cells for the purpose of tumour attenuation and
shrivelling. Satisfactory cancer treatment mandates comprehensive
elimination of a cellular tumour. Thus, a combination treatment
modality with the potential to target cancer stem cells and abutting
or distant tumour mass can be contemplated as an efficacious and
cogent clinical and therapeutic strategy [3,5]. Stem cells enunciate
growth factors and cytokines which regulate innate and cellular
immune pathways of the host. Stem cells can be distinctly manipulated
in order to circumvent the immune response mounted by the host
and can function as a cellular agents for therapeutic deliverance.
Stem cells exemplify intrinsic, tumour- tropic attributes on account of
incumbent chemokine- cancer cell interaction. Neural stem cells and
mesenchymal stem cells can actively secrete enzymes which
metamorphose non- toxic prodrugs into cytotoxic compounds.
Modifications encountered within the stem cells can assist their
localization into specialized tumour tissue where exogenously
secreted enzymes transform the prodrug into cytotoxic molecules
which culminates into deterioration of tumour cells. The
quantification, timing and site of cytotoxic drug delivery can be
regulated with accuracy. Employment of aforementioned enzyme/
prodrug treatment is also termed as “suicide gene therapy” [2,3].
Stem cells can fulfil the objective of in-situ drug repositories with the
elucidation of anti-tumour agents for prolonged duration, a feature
which surmounts the limitations of varied cancer therapy regimens
such as increasing systemic toxicity and a reduced half life of
administered drugs. TNFα- related apoptosis- inducing ligand
(TRAIL) appears to be a predominantly applicable, secreted agent
which induces apoptosis of cancer cells. Stem cells can be suitably
altered to transport growth inhibitory proteins such a interferon β
which creates a tissue microenvironment essentially non-conducive
for tumour progression. Oncolytic viruses can subjectively propagate
tumour cells. Neural stem cells transduced with oncolytic viruses can
competently adhere to malignant cells. Thus, neural stem cell
delivered tumour oncolytic viruses delineate superior anti- tumour
consequences, in contrast to singular therapeutic adoption of
oncolytic viruses [2,3]. Stem cells can be utilized as delivery agents
for nano-particles which are beneficial in instances of failure to
localize micro-metastatic lesions orin individuals with ineffective
dissemination of solid tumours or managing associated therapeutic
restrictions. Carriers of essential nano- particles are frequently
constituted of elevated concentration of insoluble chemotherapeutic
agents and can prevent therapeutic degradation. Evolving diagnostic
methodologies such as next generation genetic sequencing and
cancer genomic analysis can ensure an accurate and efficacious
therapeutic targeting with the employment of cancer stem cells.
Sequencing technologies employing singular cells and adoption of
spatial transcriptomics are cogent for precision based profiling of
individual tumour cells exemplifying specific genetic and epigenetic
cellular hierarchy [6,7]. Contemporary and versatile gene editing
techniques as adapted with CRISPR /Cas9 mechanisms can be
employed. Cancer stem cells and cancer stem cell initiated tumour
cell lineage specific potent and particular molecular signatures, as
cogitated with particular genetic mutations, genomic and protein
expression, regulation of micro-RNA, DNA methylation and pertinent
modification of histones, can be suitably discerned and edited with
an appropriate interpretation in order to configure targeted and
immune based cancer therapies [1,2] (Figures 1-4).
NSC; Neural stem cell, MSC; Mesenchymal stem cell, HSC; Haematopoietic stem cell, iPSC; induced pleuripotent stem cells
Table 1: Stem Cell Applicability in Cancer Therapy .
Figure 1: Mechanics of stem cell therapy to prevent chemoresistance and augment extinction of malignant clones .
Figure 2: Inter-relation of cytotoxic chemotherapy, cancer stem cell therapy and combination therapy to decimate malignant cells .
Figure 3: Variants of stem cells and mechanics of cancer cell and cancer stem cell interaction .
Figure 4: Comparison of conventional therapy and cancer stem cell therapy in managing tumour reoccurrence .
Transplanted stem cells can undergo a malignant transformation.
While engaging into tumour-specific microenvironment,
categorical stem cells can develop into cancer supporting cells and
correspondingly amalgamate and enhance malignant cells. The stem cell therapies can encounter immunological rejection.
Therefore, recipients of essential stem cell therapy necessitate the
administration of efficacious immune suppressive regimen with a
consequent emergence of secondary, opportunistic infections [6,7].
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