Adult stem cells

ASC

hematopoietic, mesenchymal, cardiac, intestinal, muscle, neural, retinal, skin, adipose-derived

Haematopoiesis (HSCS)

Product of haematopoietic blood cells

All blood cells in body are descended from rare population of cells - HSCs - self renew and differentiate

where do Haematopoietic come from

Predominately occur in red bone marrow (medullary)

Clos to bv (sinusoids) = niche HSC transplantation (BMwT)

Autologous

From the patient

Allogenic

Dependent on indication

Myeloablative conditioning

wipe out patients existing haematopoietic system and infuse into donor to repopulate niche and new blood cells

Rejection

Issues if HLA does not match

Pre treatment with GCSF

Graft v host disease

Non self attack

How to limit graft v host disease

decrease Tc that come from graft

enrich cells with CD34 antigen tag

Tc w/o CD34 will be washed out

Engineered HSCs

Gene editing can cure diseases that are caused by mutations in blood cells

Mesenchymal stem cells

found in BMw

take BMw biopsy

density gradient centrifugation

cell culture flask to grow

MSC niche

bmw wrapped around bv

perivascular niche

heterogenic around the body

What does ageing affect

properties

Different properties in..

Bmw

adipose

umbilical cord

Role of MSC

Tissue homeostasis and repair

provide d.c that differentiate and partake in repair

homing to distant sites of injury

secretion of factors that support wound repair by recruiting other cells types

modulate immune response

What is the response of MSC mediated by

soluble factors

ECM molecules

cell surface receptors

Therapeutic application of MSC

Hypoimmunogenic

t/prevent GvHD by dampening immune system

potential therapy following stroke, heart attack and injuries

potential delivery of therapeutic proteins

Tissue engineering

Issues with MSC

low number of donors

slow to grow

can spontaneously differentiate

Cancer

home to a cancer and can reduce angioenesis and produce miRNA - support T growth

engineered to secrete anti-tumour properties

Cell based muscular dystrophy treatment

Satellite cells cover myofibril

damage to muscle - satellite cells perfuse back to underlying muscle to repair

Dystrophin mutation

Muscle weakness and wasting

damage = no integrity and satellite cells constantly try to repair = age rapidly and stop repairing

Transfect cell therapy

mini or micro dystrophin

Issue with cell based muscular dystrophy treatment

no practical satellite cells

require IM injection to get to niche