Module 4 Multipotent Stem Cells Flashcards
What are mesenchymal stem cells?
Multipotent stem cells found in bone marrow that are important for making and repairing skeletal tissue. Also play an important role in maintaining environment of the bone marrow along with assisting in the immune response. Note that these also begin to decrease as we age.
What are adult stem cells?
Undifferentiated multipotent stem cells that reside in differentiated tissues.
Autologous vs allogenic MSC therapy?
Autologous: self donation, own MSC can be the reason for their disease, long time.
Allogeneic: Donated MSC, immediate use, cells can be selectively derived from young donors.
What are satellite cells?
They are myogenic (muscle) stem cells that help with muscle regeneration throughout the lifespan.
What is Duchenne muscular dystrophy?
X-linked disease that is most common form of MD that primarily affects boys due to absence of dystrophin, a protein involved in in the integrity of the muscle.
Signs: Swayed back, weak butt muscles, shoulder and arms held back, thin weak thighs.
What is dystrophin?
Anchor-type protein that sits just inside muscle cell membrane and tethers structural proteins inside the cell to the proteins that sit in outer surface of cell membrane.
Name the different approaches to treat DMD?
Myoblasts: Clinical trials in 1991 but other studies show mixed results in improving muscle strength. You also have to do these injections all over the body.
Satellite cells: Precursor population that can differentiate into myoblasts and repair muscle fibers or self renew and remain dormant awaiting muscle regeneration. Problem: small number of satellite cells can be extracted from biopsies and not easy to expand in culture.
MSC’s: Works but is limited in muscle regeneration
ES and IPs: Powerful as it can make any cells but ethical concerns and fear of tumor.
Stem cell scaffold will be vital for all these approaches to rebuild muscle
Chondrocytes come from which germ layer and form what 3 types of cartilage?
The mesodermal origin.
1. Hyaline (articular) cartilage: Found in joints, rib cartilage, nose, and trachea.
2. Elastic cartilage: Found in ear, epiglottis, and larynx.
3. Fibrous: Found in intervertebral discs.
Describe the components and composition of articular cartilage
Majority is a matrix made up of water with remaining solid materials:
Collagen: Resist shear stress and give structure and tensile strength
Proteoglycans and proteins: Shock absorbers
Chondrocytes: Cells that produce ECM for development and maintenance.
Define osteophyte
bony outgrowth associated with the degeneration of cartilage at joints
Describe the composition of bone
60% weight of bone is mineral (calcium and phosphate) and the rest is water and matrix, with the matrix proteins being collagen to provide strength.
Describe the bone remodeling cycle
Osteoclasts perform bone resorption (removing bone to be replaced)> reversal stage> osteoblasts perform bone formation (ossification) > osteocytes and mineralization. It’s believed that osteoporosis has an uneven relationship with osteoblasts and osteoclasts.
Describe phase of bone’s natural healing process
Reactive phase: Blood cells migrate to tissue surrounding fracture and constrict to stop bleeding.
Reparative phase: Periosteal cells close to fracture develop into chondroblasts to form hyaline cartilage while periosteal cells furthest from fracture turn into osteoblasts to form bone. The 2 tissues grow unite and is replaced with lamellar bone and finally with trabecular bone.
Remodeling Phase: Trabecular bone undergoes bone remodeling phase and becomes compact bone.
All around can take 3-5 years.
Properties of bone grafting
Graft osteogenesis: Cellular events within a donor graft which survive transplantation and synthesize new bone at recipient site.
Graft osteoinduction: New bone formation through active recruitment of host MSC from surrounding tissue. Facilitated by growth factor Bone Morphogenetic Proteins (BMPs).
Graft osteoconduction: Facilitation of blood-vessel incursion and new bone formation into graft structure.
Properties of ideal bone-graft
Biocompatible, bioresorbable, osteoconductive, osteoinductive, structurally similar, and cost-effective
Describe the bone marrow microenvironment
Niches: Local tissue microenvironments that maintain and regulate stem cells.
Hematopoiesis: Formation of blood and cellular components provides a model for understanding mammalian stem cells and their niches.
What are HSCs and why are they important?
Hematopoietic stems cells are multipotent stem cells that give rise to cells of both the blood and immune cell lineage. As these HSCs are found mostly in the bone marrow, understanding the HSC niche helps in improving regeneration following injury or transplantation.
Describe the composition of blood
55% is plasma (water with proteins that help with electrolyte balance and infection resistance)
45% is erythrocytes (RBC)
1% is leukocytes (WBC) and platelets (thrombocytes)