Stem cells are a class of undifferentiated cells that are able to differentiate into specialized cell types.

Commonly, stem
cells come from two main sources:
Embryos formed during the blastocyst phase of embryological development (embryonic stem cells) and
Adult tissue (adult stem cells).
Both types are generally characterized by their potency, or potential to differentiate into different cell types (such as
skin, muscle, bone, etc.).
Adult stem cells
Adult or somatic stem cells exist throughout the body after embryonic
development and are found inside of different types of tissue. These stem cells
have been found in tissues such as the brain, bone marrow, blood, blood vessels,
skeletal muscles, skin, and the liver. They remain in a quiescent or non-dividing
state for years until activated by disease or tissue injury.
Adult stem cells can divide or self-renew indefinitely, enabling them to generate a
range of cell types from the originating organ or even regenerate the entire
original organ. It is generally thought that adult stem cells are limited in their ability to differentiate based on their
tissue of origin, but there is some evidence to suggest that they can differentiate to become other cell types.
Embryonic stem cells
Embryonic stem cells are derived from a four- or five-day-old human embryo that is in the blastocyst phase of
development. The embryos are usually extras that have been created in IVF (in vitro fertilization) clinics where several
eggs are fertilized in a test tube, but only one is implanted into a woman.
Sexual reproduction begins when a male's sperm fertilizes a female's ovum (egg) to form a single cell called a zygote.
The single zygote cell then begins a series of divisions, forming 2, 4, 8, 16 cells, etc. After four to six days - before
implantation in the uterus - this mass of cells is called a blastocyst. The blastocyst consists of an inner cell mass
(embryoblast) and an outer cell mass (trophoblast). The outer cell mass becomes part of the placenta, and the inner cell
mass is the group of cells that will differentiate to become all the structures of an adult organism. This latter mass is
the source of embryonic stem cells - totipotent cells (cells with total potential to develop into any cell in the body).

9-week Human Embryo from Ectopic

Pregnancy [by Ed Uthman, MD]
creative commons license
In a normal pregnancy, the blastocyst stage continues until implantation of the
embryo in the uterus, at which point the embryo is referred to as a fetus. This
usually occurs by the end of the 10th week of gestation after all major organs of
the body have been created.
However, when extracting embryonic stem cells, the blastocyst stage signals when to isolate stem cells by placing the
"inner cell mass" of the blastocyst into a culture dish containing a nutrient-rich broth. Lacking the necessary
stimulation to differentiate, they begin to divide and replicate while maintaining their ability to become any cell type
in the human body. Eventually, these undifferentiated cells can be stimulated to create specialized cells.
Stem cell cultures
Human embryonic stem cell colony
[Wikipedia]
Stem cells are either extracted from adult tissue or from a dividing zygote in a
culture dish. Once extracted, scientists place the cells in a controlled culture that
prohibits them from further specializing or differentiating but usually allows them
to divide and replicate. The process of growing large numbers of embryonic stem
cells has been easier than growing large numbers of adult stem cells, but progress
is being made for both cell types.
Stem cell lines
Once stem cells have been allowed to divide and propagate in a controlled culture, the collection of healthy, dividing,
and undifferentiated cells is called a stem cell line. These stem cell lines are subsequently managed and shared among
researchers. Once under control, the stem cells can be stimulated to specialize as directed by a researcher - a process
known as directed differentiation. Embryonic stem cells are able to differentiate into more cell types than adult stem
cells.
Potency
Stem cells are categorized by their potential to differentiate into other types of cells. Embryonic stem cells are the most
potent since they must become every type of cell in the body. The full classification includes:
Totipotent - the ability to differentiate into all possible cell types. Examples are the zygote formed at egg fertilization
and the first few cells that result from the division of the zygote.
Pluripotent - the ability to differentiate into almost all cell types. Examples include embryonic stem cells and cells that
are derived from the mesoderm, endoderm, and ectoderm germ layers that are formed in the beginning stages of
embryonic stem cell differentiation.
Multipotent - the ability to differentiate into a closely related family of cells. Examples include hematopoietic (adult)
stem cells that can become red and white blood cells or platelets.
Oligopotent - the ability to differentiate into a few cells. Examples include (adult) lymphoid or myeloid stem cells.
Unipotent - the ability to only produce cells of their own type, but have the property of self-renewal required to be
labeled a stem cell. Examples include (adult) muscle stem cells.
Embryonic stem cells are considered pluripotent instead of totipotent because they do not have the ability to become
part of the extra-embryonic membranes or the placenta.
Identification of stem cells
Although there is not complete agreement among scientists of how to identify stem cells, most tests are based on
making sure that stem cells are undifferentiated and capable of self-renewal. Tests are often conducted in the
laboratory to check for these properties.
One way to identify stem cells in a lab, and the standard procedure for testing bone marrow or hematopoietic stem
cell (HSC), is by transplanting one cell to save an individual without HSCs. If the stem cell produces new blood and
immune cells, it demonstrates its potency.
Clonogenic assays (a laboratory procedure) can also be employed in vitro to test whether single cells can differentiate
and self-renew. Researchers may also inspect cells under a microscope to see if they are healthy and undifferentiated
or they may examine chromosomes.
To test whether human embryonic stem cells are pluripotent, scientists allow the cells to differentiate spontaneously
in cell culture, manipulate the cells so they will differentiate to form specific cell types, or inject the cells into an
immunosuppressed mouse to test for the formation of a teratoma (a benign tumor containing a mixture of
differentiated cells).
Research with stem cells
Scientists and researchers are interested in stem cells for several reasons. Although stem cells do not serve any one
function, many have the capacity to serve any function after they are instructed to specialize. Every cell in the body,
for example, is derived from first few stem cells formed in the early stages of embryological development. Therefore,
stem cells extracted from embryos can be induced to become any desired cell type. This property makes stem cells
powerful enough to regenerate damaged tissue under the right conditions.
Organ and tissue regeneration
Tissue regeneration is probably the most important possible application of stem cell research. Currently, organs must
be donated and transplanted, but the demand for organs far exceeds supply. Stem cells could potentially be used to
grow a particular type of tissue or organ if directed to differentiate in a certain way. Stem cells that lie just beneath the
skin, for example, have been used to engineer new skin tissue that can be grafted on to burn victims.
Cardiovascular disease treatment
A team of researchers from Massachusetts General Hospital reported in PNAS Early Edition (July 2013 issue) that they
were able to create blood vessels in laboratory mice using human stem cells.
The scientists extracted vascular precursor cells derived from human-induced pluripotent stem cells from one group
of adults with type 1 diabetes as well as from another group of “healthy” adults. They were then implanted onto the
surface of the brains of the mice.
Within two weeks of implanting the stem cells, networks of blood-perfused vessels had been formed - they lasted for
280 days. These new blood vessels were as good as the adjacent natural ones.
The authors explained that using stem cells to repair or regenerate blood vessels could eventually help treat human
patients with cardiovascular and vascular diseases.
Brain disease treatment
Additionally, replacement cells and tissues may be used to treat brain disease such as Parkinson's and Alzheimer's by
replenishing damaged tissue, bringing back the specialized brain cells that keep unneeded muscles from moving.
Embryonic stem cells have recently been directed to differentiate into these types of cells, and so treatments are
promising.
Cell deficiency therapy
Healthy heart cells developed in a laboratory may one day be transplanted into patients with heart disease,
repopulating the heart with healthy tissue. Similarly, people with type I diabetes may receive pancreatic cells to
replace the insulin-producing cells that have been lost or destroyed by the patient's own immune system. The only
current therapy is a pancreatic transplant, and it is unlikely to occur due to a small supply of pancreases available for
transplant.
Blood disease treatments
Adult hematopoietic stem cells found in blood and bone marrow have been used for years to treat diseases such as
leukemia, sickle cell anemia, and other immunodeficiencies. These cells are capable of producing all blood cell types,
such as red blood cells that carry oxygen to white blood cells that fight disease. Difficulties arise in the extraction of
these cells through the use of invasive bone marrow transplants. However hematopoietic stem cells have also been
found in the umbilical cord and placenta. This has led some scientists to call for an umbilical cord blood bank to make
these powerful cells more easily obtainable and to decrease the chances of a body's rejecting therapy.
General scientific discovery
Stem cell research is also useful for learning about human development.
Undifferentiated stem cells eventually differentiate partly because a particular
gene is turned on or off. Stem cell researchers may help to clarify the role that
genes play in determining what genetic traits or mutations we receive. Cancer and
other birth defects are also affected by abnormal cell division and differentiation.
New therapies for diseases may be developed if we better understand how these
agents attack the human body.
Another reason why stem cell research is being pursued is to develop new drugs. Scientists could measure a drug's
effect on healthy, normal tissue by testing the drug on tissue grown from stem cells rather than testing the drug on
human volunteers.
Stem cell controversy
The debates surrounding stem cell research primarily are driven by methods concerning embryonic stem cell
research. It was only in 1998 that researchers from the University of Wisconsin-Madison extracted the first human
embryonic stem cells that were able to be kept alive in the laboratory. The main critique of this research is that it
required the destruction of a human blastocyst. That is, a fertilized egg was not given the chance to develop into a
fully-developed human.
When does life begin?
The core of this debate - similar to debates about abortion, for example - centers on the question, "When does life
begin?" Many assert that life begins at conception, when the egg is fertilized. It is often argued that the embryo
deserves the same status as any other full grown human. Therefore, destroying it (removing the blastocyst to extract
stem cells) is akin to murder. Others, in contrast, have identified different points in gestational development that mark
the beginning of life - after the development of certain organs or after a certain time period.
Chimeras
People also take issue with the creation of chimeras. A chimera is an organism that has both human and animal cells
or tissues. Often in stem cell research, human cells are inserted into animals (like mice or rats) and allowed to develop.
This creates the opportunity for researchers to see what happens when stem cells are implanted. Many people,
however, object to the creation of an organism that is "part human".
Legal issues
The stem cell debate has risen to the highest level of courts in several countries. Production of embryonic stem cell
lines is illegal in Austria, Denmark, France, Germany, and Ireland, but permitted in Finland, Greece, the Netherlands,
Sweden, and the UK. In the United States, it is not illegal to work with or create embryonic stem cell lines. However,
the debate in the US is about funding, and it is in fact illegal for federal funds to be used to research stem cell lines that
were created after August 2001.
Stem cell
Stem cells are biological cellsthat can differentiate into other types of
cells and can divide to produce more of the same type of stem cells.
They are found in multicellular organisms.
In mammals, there are two broad types of stem cells: embryonic stem
cells, which are isolated from the inner cell mass of blastocysts,
and adult stem cells, which are found in various tissues.
In adultorganisms, stem cells and progenitor cells act as a repair
system for the body, replenishing adult tissues. In a
developing embryo, stem cells can differentiate into all the
specialized cells—ectoderm, endoderm and mesoderm (see induced
pluripotent stem cells)—but also maintain the normal turnover of
regenerative organs, such as blood, skin, or intestinal tissues.
There are three known accessible sources of autologous adult stem
cells in humans:
Bone marrow, which requires extraction by harvesting, that is, drilling
into bone (typically the femur or iliac crest).
Adipose tissue (fat cells), which requires extraction by
liposuction.[citation needed]
Blood, which requires extraction through apheresis, wherein blood is drawn from the donor (similar to a blood
donation), and passed through a machine that extracts the stem cells and returns other portions of the blood to the
donor.
Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting
involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank his or
her own blood for elective surgical procedures.
Adult stem cells are frequently used in various medical therapies (e.g., bone marrow transplantation). Stem cells can
now be artificially grown and transformed (differentiated) into specialized cell types with characteristics consistent
with cells of various tissues such as muscles or nerves. Embryonic cell lines and autologous embryonic stem cells
generated through somatic cell nuclear transfer or dedifferentiation have also been proposed as promising candidates
for future therapies.[1] Research into stem cells grew out of findings by
Properties[edit]
The classical definition of a stem cell requires that it possesses two properties:
Self-renewal: the ability to go through numerous cycles of cell divisionwhile maintaining the undifferentiated state.
Potency: the capacity to differentiate into specialized cell types. In the strictest sense, this requires stem cells to be
either totipotent or pluripotent—to be able to give rise to any mature cell type,
although multipotent or unipotent progenitor cells are sometimes referred to as stem cells. Apart from this it is said
that stem cell function is regulated in a feed back mechanism.
Self-renewal[edit]
Two mechanisms exist to ensure that a stem cell population is maintained:
1. Obligatory asymmetric replication: a stem cell divides into one mother cell that is identical to the original stem cell,
and another daughter cell that is differentiated.
When a stem cell self-renews it divides and does not disrupt the undifferentiated state. This self-renewal demands
control of cell cycle as well as upkeep of multipotency or pluripotency, which all depends on the stem cell. [4]
2. Stochastic differentiation: when one stem cell develops into two differentiated daughter cells, another stem cell
undergoes mitosis and produces two stem cells identical to the original.
Potency meaning[edit]

Pluripotent, embryonic stem cells originate as inner

cell mass (ICM) cells within a blastocyst. These stem
cells can become any tissue in the body, excluding a
placenta. Only cells from an earlier stage of the
embryo, known as the morula, are totipotent, able to
become all tissues in the body and the extraembryonic
placenta.

Human embryonic stem cells

A: Stem cell colonies that are not yet differentiated.
B: Nerve cells, an example of a cell typeafter differentiation.
Potency specifies the differentiation potential (the potential to differentiate into
different cell types) of the stem cell.[5]
Totipotent (a.k.a. omnipotent) stem cells can differentiate into embryonic and
extraembryonic cell types. Such cells can construct a complete, viable
organism.[5] These cells are produced from the fusion of an egg and sperm cell.
Cells produced by the first few divisions of the fertilized egg are also totipotent. [6]
Pluripotent stem cells are the descendants of totipotent cells and can differentiate
into nearly all cells,[5] i.e. cells derived from any of the three germ layers.[7]
Multipotent stem cells can differentiate into a number of cell types, but only those of a closely related family of cells.[5]
Oligopotent stem cells can differentiate into only a few cell types, such as lymphoid or myeloid stem cells. [5]
Unipotent cells can produce only one cell type, their own,[5] but have the property of self-renewal, which distinguishes
them from non-stem cells (e.g. progenitor cells, which cannot self-renew).
Identification[edit]
In practice, stem cells are identified by whether they can regenerate tissue. For example, the defining test for bone
marrow or hematopoietic stem cells(HSCs) is the ability to transplant the cells and save an individual without HSCs.
This demonstrates that the cells can produce new blood cells over a long term. It should also be possible to isolate
stem cells from the transplanted individual, which can themselves be transplanted into another individual without
HSCs, demonstrating that the stem cell was able to self-renew.
Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, in which single cells are
assessed for their ability to differentiate and self-renew.[8][9] Stem cells can also be isolated by their possession of a
distinctive set of cell surface markers. However, in vitroculture conditions can alter the behavior of cells, making it
unclear whether the cells shall behave in a similar manner in vivo. There is considerable debate as to whether some
proposed adult cell populations are truly stem cells.[citation needed]
Embryonic[edit]
Embryonic stem (ES) cells are the cells of the inner cell mass of a blastocyst, an early-
stage embryo.[10] Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of
50–150 cells. ES cells are pluripotent and give rise during development to all derivatives of the three primary germ
layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell
types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute
to the extra-embryonic membranes or the placenta.
During embryonic development these inner cell mass cells continuously divide and become more specialized. For
example, a portion of the ectoderm in the dorsal part of the embryo specializes as 'neurectoderm', which will become
the future central nervous system.[11] Later in development, neurulation causes the neurectoderm to form the neural
tube. At the neural tube stage, the anterior portion undergoes encephalization to generate or 'pattern' the basic form of
the brain. At this stage of development, the principal cell type of the CNS is considered a neural stem cell. These
neural stem cells are pluripotent, as they can generate a large diversity of many different neuron types, each with
unique gene expression, morphological, and functional characteristics. The process of generating neurons from stem
cells is called neurogenesis. One prominent example of a neural stem cell is the radial glial cell, so named because it
has a distinctive bipolar morphology with highly elongated processes spanning the thickness of the neural tube wall,
and because historically it shared some glial characteristics, most notably the expression of glial fibrillary acidic
protein (GFAP).[12][13] The radial glial cell is the primary neural stem cell of the developing vertebrateCNS, and its cell
body resides in the ventricular zone, adjacent to the developing ventricular system. Neural stem cells are committed
to the neuronal lineages (neurons, astrocytes, and oligodendrocytes), and thus their potency is restricted.[11]
Nearly all research to date has made use of mouse embryonic stem cells (mES) or human embryonic stem cells (hES)
derived from the early inner cell mass. Both have the essential stem cell characteristics, yet they require very different
environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin as
an extracellular matrix (for support) and require the presence of leukemia inhibitory factor (LIF) in serum media. A
drug cocktail containing inhibitors to GSK3B and the MAPK/ERK pathway, called 2i, has also been shown to
maintain pluripotency in stem cell culture.[14] Human ES cells are grown on a feeder layer of mouse
embryonic fibroblasts (MEFs) and require the presence of basic fibroblast growth factor (bFGF or FGF-2).[15] Without
optimal culture conditions or genetic manipulation,[16] embryonic stem cells will rapidly differentiate.
A human embryonic stem cell is also defined by the expression of several transcription factors and cell surface
proteins. The transcription factors Oct-4, Nanog, and Sox2 form the core regulatory network that ensures the
suppression of genes that lead to differentiation and the maintenance of pluripotency. [17] The cell surface antigens
most commonly used to identify hES cells are the glycolipids stage specific embryonic antigen 3 and 4 and the keratan
sulfate antigens Tra-1-60 and Tra-1-81. By using human embryonic stem cells to produce specialized cells like nerve
cells or heart cells in the lab, scientists can gain access to adult human cells without taking tissue from patients. They
can then study these specialized adult cells in detail to try and catch complications of diseases, or to study cells
reactions to potentially new drugs. The molecular definition of a stem cell includes many more proteins and continues
to be a topic of research.[18]

Mouse embryonic stem cells with fluorescent marker

Human embryonic stem cell colony on mouse embryonic fibroblast feeder layer
Fetal
The primitive stem cells located in the organs of fetuses are referred to as fetal stem
cells.[23] There are two types of fetal stem cells:
Fetal proper stem cells come from the tissue of the fetus proper, and are generally obtained after an abortion. These
stem cells are not immortal but have a high level of division and are multipotent.
Extraembryonic fetal stem cells come from extraembryonic membranes, and are generally not distinguished from
adult stem cells. These stem cells are acquired after birth, they are not immortal but have a high
level of cell division, and are pluripotent.[24]
Adult
Stem cell division and differentiation. A: stem cell; B: progenitor cell; C: differentiated cell; 1:
symmetric stem cell division; 2: asymmetric stem cell division; 3: progenitor division; 4: terminal
differentiation
Adult stem cells, also called somatic(from Greek σωματικóς, "of the body") stem cells, are
stem cells which maintain and repair the tissue in which they are found. [25] They can be
found in children, as well as adults.[26]
Pluripotent adult stem cells are rare and generally small in number, but they can be found in
umbilical cord blood and other tissues.[27] Bone marrow is a rich source of adult stem
cells,[28] which have been used in treating several conditions including liver
cirrhosis,[29] chronic limb ischemia [30] and endstage heart failure.[31] The quantity of bone
marrow stem cells declines with age and is greater in males than females during reproductive
years.[32] Much adult stem cell research to date has aimed to characterize their potency and
self- renewal capabilities.[33]DNA damage accumulates with age in both stem cells and the
cells that comprise the stem cell environment. This accumulation is considered to be
responsible, at least in part, for increasing stem cell dysfunction with aging
(see DNA damage theory of aging).[34]
Most adult stem cells are lineage-restricted (multipotent) and are generally
referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem
cell, endothelial stem cell, dental pulp stem cell, etc.).[35][36] Muse cells(multi-
lineage differentiating stress enduring cells) are a recently discovered pluripotent
stem cell type found in multiple adult tissues, including adipose, dermal
fibroblasts, and bone marrow. While rare, muse cells are identifiable by their
expression of SSEA-3, a marker for undifferentiated stem cells, and general
mesenchymal stem cells markers such as CD105. When subjected to single cell suspension culture, the cells will
generate clusters that are similar to embryoid bodies in morphology as well as gene expression, including canonical
pluripotency markers Oct4, Sox2, and Nanog.[37]
Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood
cancers through bone marrow transplants.[38] Adult stem cells are also used in veterinary medicine to treat tendon and
ligament injuries in horses.[39]
The use of adult stem cells in research and therapy is not as controversial as the use of embryonic stem cells, because
the production of adult stem cells does not require the destruction of an embryo. Additionally, in instances where
adult stem cells are obtained from the intended recipient (an autograft), the risk of rejection is essentially non-existent.
Consequently, more US government funding is being provided for adult stem cell research. [40]
Amniotic[edit]
Multipotent stem cells are also found in amniotic fluid. These stem cells are very active, expand extensively without
feeders and are not tumorigenic. Amniotic stem cells are multipotent and can differentiate in cells of adipogenic,
osteogenic, myogenic, endothelial, hepatic and also neuronal lines. [41] Amniotic stem cells are a topic of active
research.
Use of stem cells from amniotic fluid overcomes the ethical objections to using human embryos as a source of
cells. Roman Catholic teaching forbids the use of embryonic stem cells in experimentation; accordingly,
the Vaticannewspaper "Osservatore Romano" called amniotic stem cells "the future of medicine".[42]
It is possible to collect amniotic stem cells for donors or for autologuous use: the first US amniotic stem cells
bank [43][44] was opened in 2009 in Medford, MA, by Biocell Center Corporation[45][46][47] and collaborates with various
hospitals and universities all over the world.[48]
Treatments[edit]
Stem cell therapy is the use of stem cells to treat or prevent a disease or condition. Bone marrow transplant is a form
of stem cell therapy that has been used for many years without controversy.[62][63]
Advantages[edit]
Stem cell treatments may lower symptoms of the disease or condition that is being treated. The lowering of symptoms
may allow patients to reduce the drug intake of the disease or condition. Stem cell treatment may also provide
knowledge for society to further stem cell understanding and future treatments. [64]
Disadvantages[edit]
Stem cell treatments may require immunosuppression because of a requirement for radiation before the transplant to
remove the person's previous cells, or because the patient's immune system may target the stem cells. One approach
to avoid the second possibility is to use stem cells from the same patient who is being treated.
Pluripotency in certain stem cells could also make it difficult to obtain a specific cell type. It is also difficult to obtain
the exact cell type needed, because not all cells in a population differentiate uniformly. Undifferentiated cells can
create tissues other than desired types.[65]
Some stem cells form tumors after transplantation;[66] pluripotency is linked to tumor formation especially in
embryonic stem cells, fetal proper stem cells, induced pluripotent stem cells. Fetal proper stem cells form tumors
despite multipotency.[67]
Treatment[edit]

Diseases and conditions where stem cell treatment is being

investigated.
Diseases and conditions where stem cell treatment is being
investigated include:
Diabetes Rheumatoid arthritis Parkinson's Alzheimer's
Osteoarthritis[76]
Stroke and traumatic brain injury repair[77]
Learning disability due to congenital disorder [78]
Spinal cord injury repair [79]
Heart infarction [80]
Anti-cancer treatments [81]
Baldness reversal[82]
Replace missing teeth [83]
Repair hearing [84]
Restore vision [85] and repair damage to the cornea[86]
Amyotrophic lateral sclerosis [87]
Crohn's disease [88]
Wound healing [89]
Male infertility due to absence of spermatogonial stem cells [90]
Research is underway to develop various sources for stem cells, and to apply stem cell treatments
for neurodegenerative diseases and conditions, diabetes, heart disease, and other conditions.[91] Research is also
underway in generating organoids using stem cells, which would allow for further understanding of human
development, organogenesis, and modeling of human diseases.[92]
In more recent years, with the ability of scientists to isolate and culture embryonic stem cells, and with scientists'
growing ability to create stem cells using somatic cell nuclear transfer and techniques to create induced pluripotent
stem cells, controversy has crept in, both related to abortion politics and to human cloning.
Hepatotoxicity and drug-induced liver injury account for a substantial number of failures of new drugs in
development and market withdrawal, highlighting the need for screening assays such as stem cell-derived
hepatocyte-like cells, that are capable of detecting toxicity early in the drug developmentprocess.[93]