Cell fusion is an important cellular process in which several uninucleate cells (cells with a single

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom * Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucl ...

) combine to form a

multinucleate Multinucleate cells (also known as multinucleated or polynuclear cells) are eukaryotic cells that have more than one nucleus per cell, i.e., multiple nuclei share one common cytoplasm. Mitosis in multinucleate cells can occur either in a coord ...

cell, known as a

syncytium A syncytium (; plural syncytia; from Ancient Greek, Greek: σύν ''syn'' "together" and κύτος ''kytos'' "box, i.e. cell") or symplasm is a multinucleate cell (biology), cell which can result from multiple cell fusions of uninuclear cells (i.e ...

. Cell fusion occurs during differentiation of myoblasts,

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated ...

s and trophoblasts, during

embryogenesis 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 sperm ...

, and

morphogenesis Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of deve ...

. Cell fusion is a necessary event in the maturation of cells so that they maintain their specific functions throughout growth.

History

In 1847

Theodore Schwann Theodor Schwann (; 7 December 181011 January 1882) was a German physician and physiologist. His most significant contribution to biology is considered to be the extension of cell theory to animals. Other contributions include the discovery of ...

expanded upon the theory that all living organisms are composed of cells when he added to it that discrete cells are the basis of life. Schwann observed that in certain cells the walls and cavities of the cells coalesce together. It was this observation that provided the first hint that cells fuse. It was not until 1960 that cell biologists deliberately fused cells for the first time. To fuse the cells, biologists combined isolated mouse cells, with the same kind of tissue, and induced fusion of their outer membrane using the Sendai virus (a respiratory virus in mice). Each of the fused hybrid cells contained a single

with

chromosomes A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

from both fusion partners. Synkaryon became the name of this type of cell combined with a nucleus. In the late 1960s biologists successfully fused cells of different types and from different species. The hybrid products of these fusions,

heterokaryon A heterokaryon is a multinucleate cell that contains genetically different nuclei. Heterokaryotic and heterokaryosis are derived terms. This is a special type of syncytium. This can occur naturally, such as in the mycelium of fungi during sexual ...

, were hybrids that maintained two or more separate nuclei. This work was headed by Henry Harris at the University of Oxford and Nils Ringertz from Sweden's Karolinska Institute. These two men are responsible for reviving the interest of cell fusion. The hybrid cells interested biologists in the area of how different kinds of

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

affect different kinds of nuclei. The work conducted by Henry and Nils showed that proteins from one gene fusion affect gene expression in the other partner's nucleus, and vice versa. These hybrid cells that were created were considered forced exceptions to normal cellular integrity and it was not until 2002 that the possibility of cell fusion between cells of different types may have a real function in mammals.

Two types

There are two different types of cell fusion that can occur. These two types include homotypic and heterotypic cell fusion. Homotypic cell fusion occurs between cells of the same type. An example of this would be osteoclasts or myofibers being fusing together with their respective type of cells. Whenever the two nuclei merge a synkaryon is produced. Cell fusion normally occurs with nuclear fusion, but in the absence of nuclear fusion, the cell would be described as a binucleated

. A heterokaryon is the melding of two or more cells into one and it may reproduce itself for several generations. If two of the same type of cells fuse, but their nuclei do not fuse, then the resulting cell is called a syncytium. Heterotypic cell fusion occurs between cells of different types, making it the exact opposite of homotypic cell fusion. The result of this fusion is also a synkaryon produced by the merging of the nuclei, and a binucleated

in the absence of nuclear fusion. An example of this would be

Bone Marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoieti ...

Derived Cells (BMDCs) being fused with parenchymatous organs.

Four methods

There are four methods that cell biologists and biophysicists use to fuse cells. These four ways include electrical cell fusion,

polyethylene glycol Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular w ...

cell fusion, and sendai virus induced cell fusion and a newly developed method termed optically controlled thermoplasmonics. ECM 2001 Hybridoma System

Electrical cell fusion is an essential step in some of the most innovative methods in modern biology. This method begins when two cells are brought into contact by dielectrophoresis. Dielectrophoresis uses a high frequency alternating current, unlike

electrophoresis Electrophoresis, from Ancient Greek ἤλεκτρον (ḗlektron, "amber") and φόρησις (phórēsis, "the act of bearing"), is the motion of dispersed particles relative to a fluid under the influence of a spatially uniform electric f ...

in which a direct current is applied. Once the cells are brought together, a pulsed voltage is applied. The pulse voltage causes the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the ...

to permeate and subsequent combining of the membranes and the cells then fuse. After this, alternative voltage is applied for a brief period of time to stabilize the process. The result of this is that the

has mixed together and the cell membrane has completely fused. All that remains separate is the nuclei, which will fuse at a later time within the cell, making the result a

cell.

Polyethylene glycol Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular w ...

cell fusion is the simplest, but most toxic, way to fuse cells. In this type of cell fusion polyethylene glycol, PEG, acts as a dehydrating agent and fuses not only plasma membranes but also

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

membranes. This leads to cell fusion since PEG induces cell agglutination and cell-to-cell contact. Though this type of cell fusion is the most widely used, it still has downfalls. Oftentimes PEG can cause uncontrollable fusion of multiple cells, leading to the appearance of giant polykaryons. Also, standard PEG cell fusion is poorly reproducible and different types of cells have various fusion susceptibilities. This type of cell fusion is widely used for the production of

somatic cell A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells co ...

hybrids and for nuclear transfer in mammalian cloning. Sendai virus induced cell fusion occurs in four different temperature stages. During the first stage, which lasts no longer than 10 minutes, viral adsorption takes place and the adsorbed virus can be inhibited by viral antibodies. The second stage, which is 20 minutes, is pH dependent and an addition of viral antiserum can still inhibit ultimate fusion. In the third, antibody-refractory stage, viral envelope constituents remain detectable on the surface of cells. During the fourth stage, cell fusion becomes evident and HA neuraminidase and fusion factor begin to disappear. The first and second stages are the only two that are pH dependent. Thermoplasmonics induced cell fusion Thermoplasmonics is based on a near infrared (NIR) laser and a plasmonic nanoparticle. The laser which typically acts as an optical trap, is used to heat the nanoscopic plasmonic particle to very high and extremely locally elevated temperatures. Optical trapping of such a nanoheater at the interface between two membrane vesicles, or two cells, leads to immediate fusion of the two verified by both content and lipid mixing. Advantages include full flexibility of which cells to fuse and fusion can be performed in any buffer condition unlike electroformation which is affected by salt.

In human therapy

Alternative forms of restoring organ function and replacing damaged cells are needed with donor organs and tissue for transplantation being so scarce. It is because of the scarcity that biologists have begun considering the potential for

therapeutic A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis. As a rule, each therapy has indications and contraindications. There are many differe ...

cell fusion. Biologists have been discussing implications of the observation that cell fusion can occur with restorative effects following tissue damage or cell transplantation. Though using cell fusion for this is being talked about and worked on, there are still many challenges those who wish to implement cell fusion as a therapeutic tool face. These challenges include choosing the best cells to use for the reparative fusion, determining the best way to introduce the chosen cells into the desired tissue, discovering methods to increase the incidence in cell fusion, and ensuring that the resulting fusion products will function properly. If these challenges can be overcome then cell fusion may have therapeutic potential.

Microorganisms

Fungi

Plasmogamy is the stage of the sexual cycle of fungi in which two cells fuse together to share a common cytoplasm while bringing haploid nuclei from both partners together in the same cell.

''Amoebozoa''

Cell fusion ( plasmogamy or syngamy) is a stage in the ''

Amoebozoa Amoebozoa is a major taxonomic group containing about 2,400 described species of amoeboid protists, often possessing blunt, fingerlike, lobose pseudopods and tubular mitochondrial cristae. In traditional and currently no longer supported c ...

'' sexual cycle.

Bacteria

In ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

'' spontaneous zygogenesis ( Z-mating) involves cell fusion, and appears to be a form of true sexuality in

prokaryote A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Con ...

s. Bacteria that perform Z-mating are called Szp⁺.

Other uses

* To study the control of

cell division Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ar ...

and

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. ...

. * To Investigate malignant transformations. * To obtain

viral replication Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome a ...

. * For

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

and

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...

mapping. * For production of

monoclonal Monoclonality refers to the state of a line of cells that have been derived from a single clonal origin. Thus "monoclonal cells" can be said to form a single clone. The term ''monoclonal'' comes from the Ancient Greek ''monos'', meaning "alone" o ...

antibodies by producing hybridoma. * For production of Induced stem cells. * To assess protein shuttling in what is known as a ''

fusion assay''.