MC3T3 is an osteoblast precursor cell line derived from Mus musculus (mouse) calvaria. [1]
A number of derivatives of this strain have been isolated to select for varying degrees of osteogenic potential, and have been widely used as model systems in bone biology. A standard textbook calls its MC3T3-E1 sub-line "one of the most convenient and physiologically relevant systems for study of transcriptional control in calvarial osteoblasts." [2] This is a spontaneously transformed ( immortalized ) cell line. As such, it is a very convenient research tool but caution should be used when extrapolating these results to normal cells, and even more, to normal human cells. [3] [4]
When cultured on tissue culture plastic or hydrogels without cell adhesion motifs MC3T3 cells adopt a polygonal shape without considerable polarization and focal adhesions. Beyond a critical density of cell adhesion motifs MC3T3 cells polarize and form stable focal adhesions. MC3T3 cells show higher proliferation and polarization on stiff substrates. [5] [6] [7]
The MC3T3 cell line is also used for modeling skeletal tissue regeneration because its undifferentiated state is phenotypically similar to that of an osteochondroprogenitor cell. One published research article, using MC3T3-E1 cells as a model for studying cartilage regeneration, describes some of the specific limitations of the cell line for understanding behavior in human cells. [8]
In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.
Tissue engineering is a biomedical engineering discipline that uses a combination of cells, engineering, materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biological tissues. Tissue engineering often involves the use of cells placed on tissue scaffolds in the formation of new viable tissue for a medical purpose, but is not limited to applications involving cells and tissue scaffolds. While it was once categorized as a sub-field of biomaterials, having grown in scope and importance, it can is considered as a field of its own.
Osteoblasts are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts function in groups of connected cells. Individual cells cannot make bone. A group of organized osteoblasts together with the bone made by a unit of cells is usually called the osteon.
Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing blood vessel tissue, mitogenesis, i.e. proliferation, of mesenchymal cells such as fibroblasts, osteoblasts, tenocytes, vascular smooth muscle cells and mesenchymal stem cells as well as chemotaxis, the directed migration, of mesenchymal cells. Platelet-derived growth factor is a dimeric glycoprotein that can be composed of two A subunits (PDGF-AA), two B subunits (PDGF-BB), or one of each (PDGF-AB).
Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. After cells of interest have been isolated from living tissue, they can subsequently be maintained under carefully controlled conditions. They need to be kept at body temperature (37 °C) in an incubator. These conditions vary for each cell type, but generally consist of a suitable vessel with a substrate or rich medium that supplies the essential nutrients (amino acids, carbohydrates, vitamins, minerals), growth factors, hormones, and gases (CO2, O2), and regulates the physio-chemical environment (pH buffer, osmotic pressure, temperature). Most cells require a surface or an artificial substrate to form an adherent culture as a monolayer (one single-cell thick), whereas others can be grown free floating in a medium as a suspension culture. This is typically facilitated via use of a liquid, semi-solid, or solid growth medium, such as broth or agar. Tissue culture commonly refers to the culture of animal cells and tissues, with the more specific term plant tissue culture being used for plants. The lifespan of most cells is genetically determined, but some cell-culturing cells have been 'transformed' into immortal cells which will reproduce indefinitely if the optimal conditions are provided.
Intramembranous ossification is one of the two essential processes during fetal development of the gnathostome skeletal system by which rudimentary bone tissue is created. Intramembranous ossification is also an essential process during the natural healing of bone fractures and the rudimentary formation of bones of the head.
Ossification in bone remodeling is the process of laying down new bone material by cells named osteoblasts. It is synonymous with bone tissue formation. There are two processes resulting in the formation of normal, healthy bone tissue: Intramembranous ossification is the direct laying down of bone into the primitive connective tissue (mesenchyme), while endochondral ossification involves cartilage as a precursor.
Chondroblasts, or perichondrial cells, is the name given to mesenchymal progenitor cells in situ which, from endochondral ossification, will form chondrocytes in the growing cartilage matrix. Another name for them is subchondral cortico-spongious progenitors. They have euchromatic nuclei and stain by basic dyes.
Cysteine-rich angiogenic inducer 61 (CYR61) or CCN family member 1 (CCN1), is a matricellular protein that in humans is encoded by the CYR61 gene.
Homeobox protein MSX-2 is a protein that in humans is encoded by the MSX2 gene.
Periostin is a protein that in humans is encoded by the POSTN gene. Periostin functions as a ligand for alpha-V/beta-3 and alpha-V/beta-5 integrins to support adhesion and migration of epithelial cells.
Transcription factor Sp7, also called osterix (Osx), is a protein that in humans is encoded by the SP7 gene. It is a member of the Sp family of zinc-finger transcription factors It is highly conserved among bone-forming vertebrate species It plays a major role, along with Runx2 and Dlx5 in driving the differentiation of mesenchymal precursor cells into osteoblasts and eventually osteocytes. Sp7 also plays a regulatory role by inhibiting chondrocyte differentiation maintaining the balance between differentiation of mesenchymal precursor cells into ossified bone or cartilage. Mutations of this gene have been associated with multiple dysfunctional bone phenotypes in vertebrates. During development, a mouse embryo model with Sp7 expression knocked out had no formation of bone tissue. Through the use of GWAS studies, the Sp7 locus in humans has been strongly associated with bone mass density. In addition there is significant genetic evidence for its role in diseases such as Osteogenesis imperfecta (OI).
Saos-2 is a cell line derived from the primary osteosarcoma of an 11-year-old Caucasian girl in 1973 by Fogh et al. The cell line is commonly used in bone cancer research as a model for testing novel therapies.
Dental pulp stem cells (DPSCs) are stem cells present in the dental pulp, which is the soft living tissue within teeth. DPSCs can be collected from dental pulp by means of a non-invasive practice. It can be performed with an adult after simple extraction or to the young after surgical extraction of wisdom teeth. They are pluripotent, as they can form embryoid body-like structures (EBs) in vitro and teratoma-like structures that contained tissues derived from all three embryonic germ layers when injected in nude mice. DPSCs can differentiate in vitro into tissues that have similar characteristics to mesoderm, endoderm and ectoderm layers. They can differentiate into many cell types, such as odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. DPSCs were found to be able to differentiate into adipocytes and neural-like cells. DPSC differentiation into osteogenic lines is enhanced in 3D condition and hypoxia. These cells can be obtained from postnatal teeth, wisdom teeth, and deciduous teeth, providing researchers with a non-invasive method of extracting stem cells. The different cell populations, however, differ in certain aspects of their growth rate in culture, marker gene expression and cell differentiation, although the extent to which these differences can be attributed to tissue of origin, function or culture conditions remains unclear. As a result, DPSCs have been thought of as an extremely promising source of cells used in endogenous tissue engineering.
A fibrin scaffold is a network of protein that holds together and supports a variety of living tissues. It is produced naturally by the body after injury, but also can be engineered as a tissue substitute to speed healing. The scaffold consists of naturally occurring biomaterials composed of a cross-linked fibrin network and has a broad use in biomedical applications.
Arginylglycylaspartic acid (RGD) is the most common peptide motif responsible for cell adhesion to the extracellular matrix (ECM), found in species ranging from Drosophila to humans. Cell adhesion proteins called integrins recognize and bind to this sequence, which is found within many matrix proteins, including fibronectin, fibrinogen, vitronectin, osteopontin, and several other adhesive extracellular matrix proteins. The discovery of RGD and elucidation of how RGD binds to integrins has led to the development of a number of drugs and diagnostics, while the peptide itself is used ubiquitously in bioengineering. Depending on the application and the integrin targeted, RGD can be chemically modified or replaced by a similar peptide which promotes cell adhesion.
C2C12 is an immortalized mouse myoblast cell line. The C2C12 cell line is a subclone of myoblasts that were originally obtained by Yaffe and Saxel at the Weizmann Institute of Science in Israel in 1977. Developed for in vitro studies of myoblasts isolated from the complex interactions of in vivo conditions, C2C12 cells are useful in biomedical research. These cells are capable of rapid proliferation under high serum conditions and differentiation into myotubes under low serum conditions. Mononucleated myoblasts can later fuse to form multinucleated myotubes under low serum conditions or starvation, leading to the precursors of contractile skeletal muscle cells in the process of myogenesis. C2C12 cells are used to study the differentiation of myoblasts, osteoblasts, and myogenesis, to express various target proteins, and to explore mechanistic biochemical pathways.
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, chondrocytes, myocytes and adipocytes.
Craniofacial regeneration refers to the biological process by which the skull and face regrow to heal an injury. This page covers birth defects and injuries related to the craniofacial region, the mechanisms behind the regeneration, the medical application of these processes, and the scientific research conducted on this specific regeneration. This regeneration is not to be confused with tooth regeneration. Craniofacial regrowth is broadly related to the mechanisms of general bone healing.
Mohamadreza Baghaban Eslaminejad is the director of the Adult Stem Cell Lab and histology/embryology Professor at the Royan Institute where he held a multi-departmental professorship in bioengineering, tissue engineering, regenerative medicine, and stem cell therapy. Eslaminejad studies have been cited over 4000 times. He is best known for Hard Tissue Engineering and utilizing Mesenchymal stem cells for treatment of orthopedic diseases.