Cell fusion is an important cellular process in which several uninucleate cells (cells with a single nucleus) combine to form a multinucleate cell, known as a syncytium. 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 bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...

s and

trophoblast The trophoblast (from Greek language, Greek : to feed; and : germinator) is the outer layer of cells of the blastocyst. Trophoblasts are present four days after Human fertilization, fertilization in humans. They provide nutrients to the embryo an ...

s, during

embryogenesis An embryo ( ) is the initial stage of development for 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 ...

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

History

In 1839,

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

, in his '' Microscopical Researches,'' expanded upon the theory that all living organisms are composed of cells when he added that discrete cells are the basis of life. Schwann observed that in certain cells the walls and cavities of the cells coalesce ('' verschmelzen'') together. This observation 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 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 nucleus with chromosomes 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, 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 The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

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.

Types of cell fusion

Homotypic cell fusion occurs between cells of the same type. An example of this would be

osteoclasts 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 ...

or myofibers fusing together with their respective type of cells. When the two nuclei merge a synkaryon is produced. Cell fusion normally occurs with nuclear fusion, however in the absence of nuclear fusion, the cell would be described as a binucleated heterokaryon. 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. The result of this fusion is also a synkaryon produced by the merging of the nuclei, and a binucleated heterokaryon in the absence of nuclear fusion. An example of this would be

Bone Marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, 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 i ...

Derived Cells (BMDCs) being fused with parenchymatous organs.

Methods of cell fusion

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 wei ...

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 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 or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

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 heterokaryon 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 wei ...

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 In cellular biology, a somatic cell (), 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. Somatic cells compose the body of an organism ...

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 An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

. 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 Exo-α-sialidase (, sialidase, neuraminidase; systematic name acetylneuraminyl hydrolase) is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids: : Hydrolysis of α-(2→3)-, α-(2→6)-, α-(2→8)- glycosidic linkag ...

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 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 of 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.

Role in plant cells

In plants, cell fusion happens far less frequently compared to eukaryotic cells, however it does occur in some situations. Plant cells have evolved unique methods to fuse cells, largely in part due to the cell wall that surrounds plant cells. The cell wall in a plant cell will become altered prior to fusion, usually becoming thinner or even forming a bridge between cells that are about to fuse. Gamete fusion can also occur in plants.

Role in cancer progression

Cell fusion has become an area of focus for research in cancer progression in humans. When multiple types of differentiated cells fuse, the resulting cell could potentially be polyploid. Polyploid cells can be unstable due to their different genetic combinations which can often result in the cell becoming diseased. Polyploid cells can also result in unscheduled endoreplication, a process when DNA is replicated within the cell without the cell dividing, which has been linked to cancer development because of the increase in genetic instability within the cell. Metastasis, the spreading of cancer cells to different areas of the body and one of the leading causes of cancer related death, is a process that is linked to cell fusion. Cells derived from bone marrow fuse with malignant tumor cells, creating cells that have traits of each parent cell. These fused, cancerous cells have migration capabilities inherited from the bone marrow derived cell (BMDC) that allow it to travel throughout the body.

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 Taxonomy (biology), taxonomic group containing about 2,400 described species of Amoeba, amoeboid protists, often possessing blunt, fingerlike, Pseudopod#Morphology, lobose pseudopods and tubular mitochondrial cristae. In trad ...

'' sexual cycle.

Bacteria

In ''

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

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

prokaryote A prokaryote (; less commonly spelled procaryote) is a unicellular organism, single-celled organism whose cell (biology), cell lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Gree ...

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 (biology), 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 eukar ...

and

gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...

. * 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 ...

. * For

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

and

chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...

mapping. * For production of monoclonal

by producing hybridoma. * For production of induced stem cells. * To assess protein shuttling in what is known as a '' heterokaryon fusion assay''.