Lecture 13 - Stem Cellsand Tissue Engineering Flashcards
What is a stem cell?
Undifferentiated cell capable of self-renewal. Can differentiate into multiple cell types.
Function of stem cells
Maintain tissue and organ integrity by maintaining life-long production of mature, functional cells in steady state, and in response to stress
Classic stem cell properties 1) 2) 3) 4) 5) 6)
1) Renewal
2) High proliferative potential
3) Clonal repopulation
4) Multi-lineage differentiation
5) Present in low numbers
6) Quiescent in niche
Clonal repopulation example
A single haematopoietic stem cell can regenerate bone marrow
Can haematopoietic stem cells be morphologically recognised?
No
Type of cells between undifferentiated stem cells and differentiated tissue cells
Transit amplifying progenitors
What decreases a stem cell’s proliferative ability?
Lineage restriction
What determines stem cell behaviour?
Factors secreted by stromal cells, progenitor cells, soluble factors.
ECM composition
A way to study how stem cells differnetiate
Ontogeny, development
What is tissue engineering?
Process of growing new tissues and organs for the replacement, repair, improvement of damaged, diseased, poorly-functioning organs.
Epicel
A layer of keratinocytes.
For wound healing
Apligraf
A collagen matrix with dermal fibroblasts in it.
For wound healing.
Dermal regeneration template
Collagen and chondroitin layer, for healing of large wounds.
Tissue-engineering skin wound-healing technologies
Epicel
Apligraf
Dermal regeneration template
What is carticel?
For repairing cartilage defects.
Periosteal patch sewn over damaged cartilage. Injected with cultured chondrocytes.
Tissues that are easiest to engineer
Flat tissue structures, such as skin or cornea
Tissues in ascending order of complexity to engineer
Flat tissues
Hollow structures
Hollow, viscous structures (EG: bladder)
Solid organs
Major limiting factor in engineering of larger organs
Vasculature
Why have attempts to engineer skin and cartilage been more successful than other tissues?
They are less dependent on blood supply.
Cartilage is avascular.
Skin is thin enough for diffusion
Potential therapy for repairing damaged cartilage
Carticel
How thick must a tissue be in order to require vascularisation?
400 micrometers
Tissue thickness that oxygen can diffuse across
150-200 micrometers
Way around vascularisation challenge for engineered tissues
Provide biochemical signals to stimulate endogenous angiogenesis in grafted tissue
Where can cells to be engineered come from?
Autologous - From own body
Allogeneic - From another member of the same species
Pros and cons of autologous cells
No immune rejection
Need a lot of cells to make a large organ (invasive)
Slower process than using banked allogeneic cells (mightn’t be as useful for emergencies)
Pros and cons of allogeneic cells
Can use banked cells from a healthy individual
Might be rejected by the immune system
Could transmit diseases
Usual growth factors that affect stem cell differentiation
BMPs, FGF-2, VEGF, TGFb1
Necessary properties for engineered ECM 1) 2) 3) 4)
1) Biocompatible to person receiving ECM
2) Biodegradable (will slowly degrade/be remodelled in body)
3) Support transplanted or endogenous cells
4) Mimic, promote growth of endogenous ECM
What make up ECM?
Normally polypeptides, polysaccharides
Factors that give ECM different properties 1) 2) 3) 4) 5)
1) Permeability
2) Cell adhesion, biorecognition
3) Water content
4) Mechanical properties
5) Reabsorption, degradation rate
Decellularised tissues
Remove cells from an organ via a series of mechanical, enzymatic and chemical treatments.
Pros of decellularised tissues
1) Provides an acellular, 3D protein scaffold of an organ.
2) Topology and ECM profile most closely support recapitulation of organ, revascularisation, integration with surrounding tissues.
3) Can be seeded with stem cells from host. Transplantation.
4) ECM is highly conserved between species
Cons of decellularised tissues
1)
2)
1) Need an intact organ to decellularise
2) Need endothelialisation to avoid thrombosis of ECM
Where could organs for decellularisation be obtained?
1)
2)
1) Xenogenic
2) Allogenic organ donation. Perfect organs used for transplant, rest used for scaffolds
Possible method for constructing biological tissues
3D printing
Advantages of 3D printing of biological tissues 1) 2) 3) 4)
1) Precise control of architecture
2) Control density, functionality, shape to mimic organs
3) Controlled gradients in mechanical properties
4) Controlled gradients of biologically-active factors
Stem cell therapies for metabolic syndrome complications currently being investigated 1) 2) 3) 4) 5) 6) 7)
1) Diabetic neuropathy
2) Diabetic nephropathy
3) Diabetic retinopathy
4) Peripheral vascular disease
5) Ischaemic heart disease
6) Stroke
7) Arthritis
