What is Cell Fusion?

• A cell fusion occurs when two or more cells join together to form a new cell with numerous nuclei. Some cell types, such as muscle cells and osteoclasts, go through this process naturally, and it can also be generated experimentally using chemicals or electric fields.
• Cell fusion is crucial in embryonic biology for the development of multinucleated cells and tissues like syncytia and placental syncytiotrophoblasts.
• The fusion of cells has potential medical and technological applications, such as the creation of hybrid cells with novel features and the restoration of injured tissues. On the other hand, malignant disorders including cancer and viral infections can result from aberrant cell fusion processes.
• Cell fusion is a phenomenon that has been known for many years in both plant and animal cells. In plants, it is involved in the formation of multinucleate cells, such as the coenocytic cells found in some algae and fungi.
• In animals, cell fusion is a fundamental process that occurs during embryonic development, tissue regeneration, and immune responses.
• The first experimental evidence of cell fusion in animals was reported by the German biologist Johannes Holtfreter in the early 1900s. He observed that cells from different animal species could fuse together to form hybrid cells, which he called heterokaryons.
• Holtfreter’s work laid the foundation for later studies on cell fusion, which have revealed many important aspects of this process, including the molecular mechanisms involved in cell fusion and the physiological functions of multinucleated cells.
• In the mid-20th century, researchers began to use cell fusion techniques to create hybrid cells for biomedical research. One notable example is the creation of hybridomas, which are hybrid cells formed by fusing antibody-producing cells with immortal cancer cells.
• Hybridomas are used to produce monoclonal antibodies, which are important tools in biomedical research and clinical applications.
• Today, cell fusion continues to be an active area of research, with applications in biotechnology, regenerative medicine, and disease modeling.
• Advances in cell biology and molecular genetics have greatly expanded our understanding of the mechanisms and functions of cell fusion, and new techniques are being developed to manipulate cell fusion for therapeutic purposes.

Types of Cell Fusion

Cells can fuse in one of two ways. Both homotypic and heterotypic cell fusion fall into this category.

1. Homotypic cell fusion

• Homotypic cell fusion involves cells of the same type. This would be the case when osteoclasts or myofibers fuse with their respective types of cells.
• A synkaryon is created whenever two nuclei combine. In the absence of nuclear fusion, a binucleated heterokaryon describes the cell.
• A heterokaryon is the result of the fusion of two or more cells, and it is capable of self-reproduction for numerous generations. When two cells of the same type fuse without fusing their nuclei, the resulting cell is referred to as a syncytium.

2. Heterotypic cell fusion

• Contrary to homotypic cell fusion, heterotypic cell fusion occurs between cells of different kinds. In the absence of nuclear fusion, this fusion produces a binucleated heterokaryon instead of a synkaryon.
• This is illustrated by the fusion of Bone Marrow Derived Cells (BMDCs) with parenchymal organs.

3. Other types of cell fusion

There are several different types of cell fusion that can occur in both plant and animal cells. Here are some examples:

1. Syncytial fusion: This type of fusion involves the merging of two or more cells into a single, multinucleated cell. This is a common process in muscle and placental cells.
2. Parasexual fusion: This occurs when two genetically distinct cells fuse together, but their nuclei do not mix. Instead, they undergo a process of genomic rearrangement to produce a new hybrid genome.
3. Heterokaryon fusion: This is the fusion of two cells from different species or with different genetic backgrounds to form a hybrid cell with two or more nuclei. This type of fusion is often used in research to study the regulation of gene expression and the function of specific proteins.
4. Somatic cell nuclear transfer (SCNT): This is a type of fusion that involves the transfer of a nucleus from one cell into an enucleated recipient cell. This technique has been used to create cloned animals, such as Dolly the sheep.
5. Viral fusion: This occurs when a virus fuses its envelope with the cell membrane of a host cell, allowing the virus to enter the cell and replicate.

a Cells of the same lineage combine to form a syncytium, a cell with numerous nuclei. The combined cell may have a modified phenotypic and new functions, including barrier creation.
b When cells of various lineages unite, the result is a heterokaryon, a cell with several nuclei. The joined cells may have experienced phenotypic reversal or transdifferentiation.
c Cells of different or the same lineage fuse to form a single-nucleated cell called a synkaryon. Novel functions of the merged cell may include phenotypic reversion, transdifferentiation, and cell division. If nuclear fusion occurs, the merged nucleus initially contains the total chromosomal content of both fusion partners (4N), however chromosomes are ultimately destroyed and/or re-sorted (see arrows). In the absence of nuclear fusion, a heterokaryon (or syncytium) can transform into a synkaryon by shedding its whole nucleus.

These are just a few examples of the different types of cell fusion that can occur. Each type of fusion has unique molecular and cellular mechanisms, and can have different biological and physiological effects. Understanding the mechanisms and functions of these different types of fusion can help us develop new therapies and treatments for a variety of diseases and conditions.

Methods of Cell Fusion

Cell biologists and biophysicists utilize four strategies to fuse cells. These four methods consist of electrical cell fusion, polyethylene glycol cell fusion, Sendai virus-induced cell fusion, and a recently developed technique known as optically controlled thermoplasmonics.

1. Electrical cell fusion

• Electrical cell fusion is a crucial step in some of the most cutting-edge techniques in contemporary biology. Dielectrophoresis is used to bring two cells into touch to initiate this process.
• Dielectrophoresis employs a high frequency alternating current, in contrast to electrophoresis, which employs a direct current.
• After bringing the cells together, a pulsed voltage is delivered. The voltage pulse causes the cell membrane to permeate, and subsequent membrane fusion leads the cells to merge.
• After this, a brief period of alternate voltage is applied to stabilize the process. As a result, the cytoplasm has merged and the cell membrane has fused in its whole.
• All that remains distinct are the nuclei, which will eventually combine within the cell to form a heterokaryon cell.

2. Polyethylene glycol cell fusion

• Cell fusion using polyethylene glycol is the simplest but most hazardous method. PEG works as a dehydrating agent and fuses not only plasma membranes but also intracellular membranes in this kind of cell fusion.
• As PEG stimulates cell agglutination and cell-to-cell contact, this results in cell fusion. Although this is the most common type of cell fusion, it is not without flaws.
• Frequently, PEG can trigger the uncontrolled fusing of several cells, resulting in the formation of enormous polykaryons.
• In addition, typical PEG cell fusion is difficult to reproduce, and the susceptibility of various cell types to fuse varies. This sort of cell fusion is commonly utilized to create somatic cell hybrids and for nuclear transfer in mammalian cloning.

3. Sendai virus induced cell fusion

• Cell fusion mediated by the Sendai virus happens in four distinct temperature stages. During the first stage, which lasts no longer than 10 minutes, viral adsorption occurs, and viral antibodies can block the adsorbed virus.
• The 20-minute second stage is pH-dependent, and the presence of viral antiserum can still block final fusion. At the third, antibody-resistant stage, viral envelope components are still identifiable on the cell surface.
• During the fourth stage, cell fusion becomes apparent and HA neuraminidase and fusion factor begin to degrade. The only pH-dependent stages are the first and second stages.

4. Thermoplasmonics induced cell fusion

• Thermoplasmonics stimulated cellular fusion Near infrared (NIR) lasers and plasmonic nanoparticles are the basis of thermoplasmonics.
• The laser, which normally functions as an optical trap, is utilized to heat the nanoscopic plasmonic particle to temperatures that are incredibly high and significantly increased locally.
• Trapping such a nanoheater optically at the interface of two membrane vesicles or two cells results in the immediate fusion of the two, which is confirmed by the mixing of their contents and lipids.
• In contrast to electroformation, which is impacted by salt, fusion can be accomplished under any buffer environment.

Significance of Cell Fusion

• Development: During embryonic development, cell fusion plays a critical role in the formation of syncytia, which are multinucleated cells that perform specialized functions, such as the formation of skeletal muscle fibers and the syncytiotrophoblast layer in the placenta.
• Tissue regeneration: Cell fusion is essential for tissue regeneration and repair, particularly in the skeletal muscle and bone marrow. The fusion of myoblasts (muscle precursor cells) results in the formation of mature multinucleated muscle fibers, while osteoclasts (bone-resorbing cells) are formed by the fusion of monocytes.
• Cancer: In cancer, cell fusion has been implicated in tumor progression and metastasis. Tumor cells can fuse with non-transformed cells, such as immune cells and stromal cells, resulting in hybrid cells that exhibit altered properties, such as increased invasiveness and drug resistance.
• Reproduction: Cell fusion is essential for fertilization, as it involves the fusion of the sperm and egg cells to form a zygote.
• Research: Cell fusion is also a valuable tool in biological research, particularly in cell biology, immunology, and genetics. Researchers use cell fusion to create hybrid cells with unique properties, such as the fusion of cancer cells with normal cells to study cancer progression or the fusion of somatic cells with embryonic stem cells to create induced pluripotent stem cells (iPSCs).

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