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A stem cell line is a group of
stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
s that is cultured
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
and can be propagated indefinitely. Stem cell lines are derived from either animal or human tissues and come from one of three sources:
embryonic stem cell Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre- implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consi ...
s,
adult stem cell Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells (from Greek σωματικóς, ...
s, or
induced stem cells Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor (multipotent – iM ...
. They are commonly used in research and regenerative medicine.


Properties

By definition, stem cells possess two properties: (1) they can self-renew, which means that they can divide indefinitely while remaining in an undifferentiated state; and (2) they are
pluripotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta. According to Latin terms, Pluripotentia means the ability for many thin ...
or
multipotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta. According to Latin terms, Pluripotentia means the ability for many thin ...
, which means that they can differentiate to form specialized cell types. Due to the self-renewal capacity of stem cells, a stem cell line can be cultured ''in vitro'' indefinitely. A stem-cell line is distinctly different from an
immortalized cell line An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells ...
, such as the
HeLa HeLa (; also Hela or hela) is an immortalized cell line used in scientific research. It is the oldest and most commonly used human cell line. The line is derived from cervical cancer cells taken on February 8, 1951, named after Henrietta La ...
line. While stem cells can propagate indefinitely in culture due to their inherent properties, immortalized cells would not normally divide indefinitely but have gained this ability due to mutation. Immortalized cell lines can be generated from cells isolated from tumors, or mutations can be introduced to make the cells immortal. A stem cell line is also distinct from primary cells. Primary cells are cells that have been isolated and then used immediately. Primary cells cannot divide indefinitely and thus cannot be cultured for long periods of time in vitro.


Types and methods of derivation


Embryonic stem cell line

An
embryonic stem cell Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre- implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consi ...
line is created from cells derived from the
inner cell mass The inner cell mass (ICM) or embryoblast (known as the pluriblast in marsupials) is a structure in the early development of an embryo. It is the mass of cells inside the blastocyst that will eventually give rise to the definitive structures of ...
of a
blastocyst The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...
, an early stage, pre-implantation
embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
. In humans, the blastocyst stage occurs 4–5 days post fertilization. To create an embryonic stem cell line, the inner cell-mass is removed from the blastocyst, separated from the trophoectoderm, and cultured on a layer of supportive cells in vitro. In the derivation of human embryonic stem cell lines, embryos left over from
in vitro fertilization In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating an individual's ovulatory process, removing an ovum or ova (egg or eggs) ...
(IVF) procedures are used. The fact that the blastocyst is destroyed during the process has raised controversy and ethical concerns. Embryonic stem cells are
pluripotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta. According to Latin terms, Pluripotentia means the ability for many thin ...
, meaning they can differentiate to form all cell types in the body. In vitro, embryonic stem cells can be cultured under defined conditions to keep them in their pluripotent state, or they can be stimulated with biochemical and physical cues to differentiate them to different cell types.


Adult stem cell line

Adult stem cell Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells (from Greek σωματικóς, ...
s are found in juvenile or adult tissues. Adult stem cells are
multipotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta. According to Latin terms, Pluripotentia means the ability for many thin ...
: they can generate a limited number of differentiated cell types (unlike pluripotent embryonic stem cells). Types of adult stem cells include
hematopoietic stem cell Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within t ...
s and
mesenchymal stem cell Mesenchymal stem cells (MSCs) also known as mesenchymal stromal cells or medicinal signaling cells are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage c ...
s. Hematopoietic stem cells are found in the bone marrow and generate all cells of the immune system all blood cell types. Mesenchymal stem cells are found in umbilical cord blood, amniotic fluid, and adipose tissue and can generate a number of cell types, including
osteoblast Osteoblasts (from the Greek language, Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cell (biology), cells with a single Cell nucleus, nucleus that synthesize bone. However, in the p ...
s,
chondrocyte Chondrocytes (, from Greek χόνδρος, ''chondros'' = cartilage + κύτος, ''kytos'' = cell) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteog ...
s, and
adipocyte Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...
s. In medicine, adult stem cells are mostly commonly used in bone marrow transplants to treat many bone and blood cancers as well as some autoimmune diseases. (See
Hematopoietic stem cell transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produc ...
) Of the types of adult stem cells have successfully been isolated and identified, only mesenchymal stem cells can successfully be grown in culture for long periods of time. Other adult stem cell types, such as hematopoietic stem cells, are difficult to grow and propagate in vitro. Identifying methods for maintaining hematopoietic stem cells in vitro is an active area of research. Thus, while mesenchymal stem cell lines exist, other types of adult stem cells that are grown in vitro can better be classified as primary cells.


Induced pluripotent stem-cell (iPSC) line

Induced pluripotent stem cell Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka's lab in Kyoto, Japan, who showed in ...
(iPSC) lines are pluripotent stem cells that have been generated from adult/somatic cells. The method of generating iPSCs was developed by
Shinya Yamanaka is a Japanese stem cell researcher and a Nobel Prize laureate. He serves as the director of Center for iPS Cell (induced Pluripotent Stem Cell) Research and Application and a professor at the Institute for Frontier Medical Sciences at Kyoto ...
's lab in 2006; his group demonstrated that the introduction of four specific genes could induce somatic cells to revert to a pluripotent stem cell state. Compared to embryonic stem-cell lines, iPSC lines are also pluripotent in nature but can be derived without the use of human embryos—a process that has raised ethical concerns. Furthermore, patient-specific iPSC cell lines can be generated—that is, cell lines that are genetically matched to an individual. Patient-specific iPSC lines have been generated for the purposes of studying diseases and for developing patient-specific medical therapies.


Methods of culture

Stem-cell lines are grown and maintained at specific temperature and atmospheric conditions (37 degrees Celsius and 5% ) in incubators. Culture conditions such as the cell
growth medium A growth medium or culture medium is a solid, liquid, or semi-solid designed to support the growth of a population of microorganisms or cells via the process of cell proliferation or small plants like the moss ''Physcomitrella patens''. Differen ...
and surface on which cells are grown vary widely depending on the specific stem cell line. Different biochemical factors can be added to the medium to control the cell phenotype—for example to keep stem cells in a pluripotent state or to differentiate them to a specific cell type.


Uses

Stem-cell lines are used in research and regenerative medicine. They can be used to study stem-cell biology and early human development. In the field of regenerative medicine, it has been proposed that stem cells be used in cell-based therapies to replace injured or diseased cells and tissues. Examples of conditions that researchers are working to develop stem-cell-based treatments for include neurodegenerative diseases, diabetes, and spinal cord injuries.


Ethical issues

There is controversy associated with the derivation and use of human embryonic stem cell lines. This controversy stems from the fact that derivation of human embryonic stem cells requires the destruction of a blastocyst-stage, pre-implantation human embryo. There is a wide range of viewpoints regarding the moral consideration that blastocyst-stage human embryos should be given.


Access to human embryonic stem-cell lines


United States

In the United States, Executive Order 13505 established that federal money can be used for research in which approved human embryonic stem-cell (hESC) lines are used, but it cannot be used to derive new lines. The National Institutes of Health (NIH) Guidelines on Human Stem Cell Research, effective July 7, 2009, implemented the Executive Order 13505 by establishing criteria which hESC lines must meet to be approved for funding. The NIH Human Embryonic Stem Cell Registry can be accessed online and has updated information on cell lines eligible for NIH funding. There are 486 approved lines as of January 2022. Studies have found that approved hESC lines are not uniformly used in the US data from cell banks and surveys of researchers indicate that only a handful of the available hESC lines are routinely used in research. Access and utility are cited as the two primary factors influencing what hESC lines scientists choose to work with. A 2011 survey of stem cell scientists in the US who use hESC lines in their research found that 54% of respondents used two or fewer lines and 75% used three or fewer lines. Another study tracked cell-line requests fulfilled from the largest US repositories, the National Stem Cell Bank (NSCB) and the Harvard Stem Cell Institute (HSCI; Cambridge, MA, USA), for the periods March 1999 – December 2008 (for NSCB) and April 2004 – December 2008 (for HSCI). For NSCB, out of twenty-one approved cell lines, 77% of requests were for two of the lines (H1 and H9). For HSCI, out of the 17 lines requested more than once, 24.7% of requests were for the two most commonly requested lines.


See also

*
Stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
*
Embryonic stem cell Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre- implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consi ...
*
Induced pluripotent stem cell Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka's lab in Kyoto, Japan, who showed in ...
*
Induced stem cells Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor (multipotent – iM ...
*
Adult stem cell Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells (from Greek σωματικóς, ...
*
Cell culture Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This te ...
*
Immortalised cell line An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells ...
* Stem-cell controversy * Stem-cell treatments *
Regenerative Medicine Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by st ...


References

{{Reflist Stem cells Induced stem cells Cell culture