animal Animals are multicellular, eukaryotic organisms in the Biology, biological Kingdom (biology), kingdom Animalia (). With few exceptions, animals heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, ...

and Human biology, a tendon cell is a cell that makes up

tendon A tendon or sinew is a tough band of fibrous connective tissue, dense fibrous connective tissue that connects skeletal muscle, muscle to bone. It sends the mechanical forces of muscle contraction to the skeletal system, while withstanding tensi ...

s, the bands of connective tissue that connects muscles to bones. Tendon cells, also known as tenocytes or tendon fibroblasts, are specialized cells that contribute to the structure, function, and repair of tendons in the body. Tendons are fibrous tissues that connect muscles to bones, and tendon cells play a vital role in maintaining tendon homeostasis and facilitating healing following injury.

Function

Tendon cells are primarily responsible for the production and maintenance of the tendon extracellular matrix (ECM), which consists mainly of collagen fibers. These cells are involved in synthesizing collagen and other ECM components that provide tendons with tensile strength. Tendon cells also participate in remodeling the ECM in response to mechanical stress and injury.

Structure

Tendon cells are typically elongated, spindle-shaped cells that align along the axis of tendon fibers. They contain large amounts of rough endoplasmic reticulum to support the production of collagen. The unique structure of tendon cells allows them to withstand mechanical stress and contribute to tendon strength and flexibility.

Types

* Tenocytes: The mature tendon cells responsible for maintaining tendon structure and function. * Tendon Progenitor Cells (TPCs): These cells are involved in tendon repair and regeneration, particularly after injury. * Fibroblasts: A more general type of connective tissue cell, fibroblasts in tendons also contribute to the synthesis of ECM components.

Development and Differentiation

Tendon cells originate during fetal development from mesenchymal stem cells, which differentiate into tenocytes and fibroblasts. In adults, tendon cells maintain the integrity of the tendon through continuous remodeling. The regeneration capacity of tendon cells is limited, which can make healing after injury slower compared to other tissues. Research has identified several molecular players that govern tendon cell differentiation and development. These include transcription factors (e.g., Scleraxis (Scx), Sox9) and signaling pathways (e.g., BMPs, Wnt, Fgf), which regulate tendon precursor cells and their transition into mature tenocytes. However, the full spectrum of molecular regulators remains largely unknown, and understanding these molecular networks is a key goal for future research.

Vertebrates

Tendon cells, or tenocytes, are elongated fibroblast type cells. The cytoplasm is stretched between the

collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

fibres of the tendon. They have a central

cell nucleus The cell nucleus (; : nuclei) is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have #Anucleated_cells, ...

with a prominent

nucleolus The nucleolus (; : nucleoli ) is the largest structure in the cell nucleus, nucleus of eukaryote, eukaryotic cell (biology), cells. It is best known as the site of ribosome biogenesis. The nucleolus also participates in the formation of signa ...

. Tendon cells have a well-developed rough endoplasmic reticulum and they are responsible for synthesis and turnover of tendon fibres and ground substance.

Invertebrates

Tendon cells form a connecting epithelial layer between the

muscle Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...

and shell in

molluscs Mollusca is a phylum of protostome, protostomic invertebrate animals, whose members are known as molluscs or mollusks (). Around 76,000 extant taxon, extant species of molluscs are recognized, making it the second-largest animal phylum ...

. In

gastropods Gastropods (), commonly known as slugs and snails, belong to a large taxonomic class of invertebrates within the phylum Mollusca called Gastropoda (). This class comprises snails and slugs from saltwater, freshwater, and from the land. Ther ...

, for example, the retractor muscles connect to the shell via tendon cells. Muscle cells are attached to the collagenous myo-tendon space via hemidesmosomes. The myo-tendon space is then attached to the base of the tendon cells via basal hemidesmosomes, while apical hemidesmosomes, which sit atop microvilli, attach the tendon cells to a thin layer of

. This is in turn attached to the shell via organic fibres which insert into the shell. Molluscan tendon cells appear columnar and contain a large basal

. The

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 ...

is filled with granular

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

and sparse golgi. Dense bundles of

microfilaments Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other p ...

run the length of the cell connecting the basal to the apical hemidesmosomes.

Injury and Repair

When tendons are injured, tendon cells are activated to promote repair, but this process can be slow. Recent research has focused on improving tendon healing through therapies such as stem cell injections, growth factors, and tissue-engineered approaches to enhance tendon cell activity and regeneration.

Tendonopathy

Tendinopathy refers to a spectrum of tendon disorders, including tendinitis and tendinosis, characterized by pain, swelling, and impaired function of the tendon. Tendon rupture involves the partial or complete tear of the tendon, which can occur acutely or as a result of chronic degeneration. Both conditions are common in athletes and the aging population, but effective treatments and therapies remain limited due to an incomplete understanding of the underlying biology.

Challenges in Tendon Cell Research

Despite their importance in tendon function and repair, expanding tenocytes in vitro for therapeutic purposes remains a significant challenge. The main hurdle in this area is the phenotypic drift that occurs during the in vitro culture of tenocytes. These cells tend to lose their characteristic elongated morphology and tenogenic properties when grown in culture for extended periods. This drift complicates their use in regenerative medicine and tendon tissue engineering, as it limits the cells' ability to maintain their functional and structural roles in tendon repair. One of the primary reasons for the phenotypic drift of tenocytes in culture is the loss of their characteristic elongated shape. Under normal conditions, tenocytes are elongated to facilitate the interaction with surrounding collagen fibers. This morphology is important for maintaining their function in the tendon tissue. However, when cultured in conventional conditions, tenocytes often undergo a morphological shift, adopting a more rounded shape and losing their specialized functionality. This drift in phenotype can be detrimental to their ability to effectively regenerate tendon tissue. Given the challenges associated with in vitro tenocyte expansion and autologous tenocyte availability, alternative strategies need to be explored. Some of the promising approaches include: # Stem cell-based therapies: Mesenchymal stem cells or induced pluripotent stem cells (iPSCs) can be differentiated into tenocytes in vitro. These cells offer an almost unlimited source for expanding tendon-like cells, which could be used for tendon repair and regeneration. However, their differentiation protocols still require optimization to achieve functional tenocytes that closely mimic the native tendon environment. # Tendon tissue engineering: Combining tenocytes (or stem cells) with biomaterials, such as scaffolds, that mimic the natural tendon extracellular matrix is a promising avenue for tendon repair. These scaffolds can provide structural support and guide the differentiation and organization of tendon cells. # Gene editing: Techniques like CRISPR-Cas9 could be used to enhance the tenogenic properties of stem cells or to correct defects in autologous tenocytes derived from the patient’s own tissue. This approach could allow for more controlled and efficient tendon regeneration.

References

Human cells Connective tissue cells GAG secreting cells {{Cell-biology-stub