Lecture 3: MSC-Derived Connective Tissue Flashcards
Mesenchymal stem cell
Progenitor for all resident tissue cells, differentiates from ESC
Basic components of all connective tissue
- Cells
- Fibers
- Ground substance
Extracellular matrix
Composed of all extracellular parts of connective tissue (fibers + ground substance)
Type II collagen
Primary part of hyaline cartilage. Very tight, hydrated ECM that makes cell motility impossible.
Type I collagen
Dominant large fiber of CT. Forms ropes/sheets for structural and space-filling roles as procollagen linked into fibrils. More type I = more density
Hydrogels
Bioengineered compounds that mimic CT properties
Mesenchymal stem cell
Progenitor cell for all stromal cells of CT compartments (adipocytes, fibroblasts, muscle)
Unilocular adipocytes
Also known as white fat cells occur in white adipose tissue and primarily act as energy storage. Will often undergo hypertrophy instead of dividing.
Multilocular adipocytes
Also known as brown fat cells, occurring in brown adipose tissue. Specialized for thermogenesis.
Beige fat cells
Transitional stage between from white fat to brown fat. Multilocular thermogenic cells found in white adipose tissue
Fat depots
Areas of white fat collections, e.g. the subcutaneous, visceral, and intermuscular fat.
Fibroblasts
Cells responsible for production, remodeling, and degradation of ECM fibers and ground substance
Myofibroblasts
Myosin-producing fibroblast subtype. Responsible for generating force, e.g. in wound closure
Type III collagen
Dominant small fiber of CT and in the mesenchyme (embryonic undifferentiated CT). Provides support in regions with more cells. More type III vs type I typically makes looser CT. AKA reticular fibers
Elastin
Main protein in elastic fibers, along with some fibrillins. Provide stretchiness in CT.
Type IV collagen
Forms the lamina densa of external/basement membranes
Type VII collagen
Forms anchoring filaments in lamina reticularis of external/basement membranes
Type X collagen
Supportive role necessary for deposition of type I collagen at bone growth plates
Type V collagen
Necessary for fibrillation of type I and III collagens.
Classes of fibrous CT
- Loose
- Dense irregular
- Dense sheet-like
- Dense regular
Loose connective tissue
Contains a higher proportion of type III collagen and ground substance. Fibers have irregular orientation, fills layers that allow cell motility and also loose-cell-ball organs e.g. spleen, lymph nodes
Dense irregular connective tissue
Mostly type I collagen arranged in 3 dimensions; default space-filling CT. Generally does not allow cell motility (but density is on a spectrum).
Dense sheet-like connective tissue
Mostly type I collagen arranged in 2D sheets. Compartmentalization of CT like bones, joints - forms sheaths and fascia
Dense regular connective tissue
Mostly type I collagen aligned in 1 dimension. Highly regulated development via other collagens and mostly only found in tendons/ligaments.
Matrix metalloproteases (MMPs)
Class of compounds that degrade collagens, elastins, and other CT parts. Some are specific to collagen type.
Ground substance
Occupies space between CT cells and fibers. Consists of highly hydrated proteoglycan complexes and glycoproteins
Proteoglycan
Large molecule with backbone (e.g. hyaluronic acid), proteoglycan stems, and glycosaminoglycans (GAGs) with associated water molecules
Peri-neuronal nets (PNNs)
EC proteoglycan structure that surrounds neurons. Guide/deter the growth trajectory of new axons and formation of new connections.
Examples of glycosaminoglycans
Dermatan sulfate, heparan sulfate, keratan sulfate, chondroitin sulfate
Matrisome
The entire ECM of the CT in a given location
Matrisome core components
- ECM glycoproteins (non-fibrillar proteins)
- Collagens
- Proteoglycans
- Associated proteins, regulators, secreted factors
Cellular CT disorders
Often immune-mediated; e.g. immune responses can reduce the fibrous fraction and weaken CT walls
Fibrous CT disorders
Fibroproliferative responses, e.g. cysts, loss of flexibility, keloid scars, organ LOF due to scarring. Some genetic fiber disorders e.g. Marfan
Ground substance CT disorders
Imbalance of fluid flow can lead to edema. Caused by occlusion of fluid drainage or inadequate circulation.
Uncoupling protein
UCP-1 determines if fat will be thermogenic; changes mitochondria product from ATP to heat
CT origin
Mesoderm layer. After folding, mesoderm comes to fill space between ectoderm (outside) and endoderm (gut tube)
Trans-differentiation
Conversion of one cell type to another, e.g. adipocytes <-> muscle <-> fibroblasts
De-differentiation
Process by which cells become less specialized and return to earlier state in lineage, e.g. adipocyte/fibroblast/muscle -> MSC
Adipocyte hypoxia
Adipocyte hypertrophy can outgrow oxygen supplies, leading to cell death and inflammation; may mediate many obesity-related disorders.
Highly fluid CT
Blood and lymph are examples of highly fluid and cellular CT, low in fibers
Highly fibrous CT
Tendons and ligaments are examples of highly fibrous CT, with low cells (and low cell motility) and lower ground substance
Functional classes of collagen
- Fibrillar (Type I, II, III)
- Fibrillar anchoring (Type VII)
- Meshwork (Type IV)
- Other nonfibrillar (many)
External membrane
Membrane that surrounds adipose and muscle tissue
Basement membrane
Membrane on basal side of epithelia (always have polarity). External = basement when epithelium is attached.
