Fibrosis & FibrocytesGordon CookeConway InstituteUCD

What’s a Fibrocyte?

• Fibrocytes are blood-borne cells with the ability to produce extracellular matrix (ECM)

• The cells express the hematopoietic cell surface markers CD34+, CD45+, as well as fibroblast markers such as collagen

• The fact that these cells circulate in blood, express collagen and the leukocyte cell surface marker CD 34 makes them unique among connective tissue cells

• Previous studies looking at wound injury have estimated that up to 10% of the cells that infiltrate sites of acute injury may be fibrocytes

What’s a Fibrocyte?

• The cells express CD34 cell surface marker indicating that they are derived from the bone marrow. CD45 indicates that they are from the leukocyte family.

• They can under prolonged culture acquire a myfibroblast phenotype (increase expression of ASMA)

• They traffic to the longs in response to the chemokine CXCL12 and have been thought to be involved in the pathogenesis of pulmonary fibrosis

What do they do and why are they important?• Fibrocytes are a sub-population of peripheral blood cells

that produce connective tissue proteins such as collagens and alpha smooth muscle actin

• It’s suggested that they play a pivotal role in wound healing and tissue repair by:

– serving as potent antigen presenting cells– producing important cytokines, chemokines and growth factors necessary

for wound repair– secreting essential extracellular matrix proteins involved in wound repair– serving as a contractile force in wound closure via alpha smooth muscle

actin expression (ASMA).– promoting angiogenesis (growth of new blood vessels from pre-existing

vessels)

• Fibrocytes have been identified in scar tissue and more recently in the lung tissue of IPF (Idiopathic Pulmonary Fibrosis) patients

Why are we interested in them?• Sarcoidosis, also called sarcoid (from the Greek 'sark'

and 'oid' meaning "flesh-like") is an immune system disorder that most commonly arises in young adults

• Can be hard to diagnose early• Many patients do not require treatment and recover• Difficult to identify those who’ll need treatment from those who

don’t

• Treatment is with corticosteroids

• Is it possible to predict who will develop severe sarcoidosis, and therefore will need treatment, based on their fibrocyte count?

The Plan

• Long term study (years)• Enrol patients• Isolate fibrocytes and see can we detect them via

FACS• See is it possible to detect and identify fibrocytes

directly from whole blood without culture• Determine if there are differences between mild and

severe sarcoidosis• Do circulating fibrocyte levels in blood vary over time

in sarcoid patients?• Can we predict on presentation whether a patient

needs treatment now or will recover themselves?

How are we studying them?

• Cells are then analysed by FACS for:CD34/CD45 and Collagen Ior CXCR4 Collagen I