Monitoring Inflammatory Biomarkers in Patients with Chronic Obstructive Pulmonary Disorder
Chronic obstructive pulmonary disease (COPD) is the most common respiratory disease in the world and is characterised by pulmonary and systemic inflammation. It is a progressive disorder with no effective treatments. Recently, infusions of mesenchymal stromal cells (MSC) have been successful in clinical trials of various inflammatory diseases. MSC possess anti-inflammatory properties and have been shown to enhance the function of immunosuppressive T regulatory cells (T-regs) and myeloid derived suppressor cells (MDSC). As well, MSC are capable of modulating pro-inflammatory responses, particularly monocytic and dendritic responses, which are impaired in COPD. However, the effect and mechanism of action of MSC post-infusion are poorly characterised, particularly in COPD. The challenge of this study was to determine the effect of MSC infusions on the inflammatory state of patients with COPD, by analysing biomarkers and immune cell populations.
How did the facility help?
The CTTWA facility provided access to equipment to allow the analysis of immune cell populations to be performed. Under THD NCRIS program, CTTWA was able to purchase a Flow cytometer for the fluorescent labelling and analysis of cell populations in patient and product samples. Although the Flow cytometer is primarily used for the characterisation of clinical products, the equipment is also made available to researchers, including external groups. The equipment is maintained by CTTWA, under the CTTWA Quality Management system, and its operation is compliant with TGA and NATA requirements. The CTTWA facility has trained staff to assist in the operation of the equipment. The CTTWA Flow cytometer is the only one on the Royal Perth Hospital campus which is available to researchers. Without access to the equipment, analysing the acute effect of MSC infusions in these COPD patients, participating in the clinical trial, would not have been possible.
Analysis of biomarkers showed that most (IL-6, IP-10, F2-IsoP) were significantly reduced after MSC infusion. Analysis of cell populations using the Flow cytometer analysis demonstrated that T-regs and MDSC levels increased, while proportions of monocytes and dendritic cell populations were shifted towards a more regulatory phenotype following MSC infusion. This data is novel and shows that MSC therapy in COPD patients reduces systemic inflammation within a week of infusion. The study is helping to understand the mechanism of MSC mediated immune regulation.
Cell and Tissue Therapies WA (CTTWA) has been actively involved in the translation of health discoveries since the commissioning of the manufacturing facility at Royal Perth Hospital in 2006. The core business of CTTWA is the manufacture and provision of clinical products and services for the WA Health sector. This activity basis, along with a close interface with diverse medical specialities, has placed CTTWA in a strong position to embrace and assist in the translation of the emerging biotherapies. It has extensive experience in biotherapeutic manufacturing and with regulatory requirements.
The manufacturing facility consists of five clean rooms, specified as ISO class 7, outfitted and supported with appropriate infrastructure. It operates under TGA licence and with FACT-JACIE and NATA accreditation. CTTWA is supported by WA Department of Health through an operational budget and staffing and services access. The NCRIS program has been instrumental in providing assistance for the initiation of clinical trials to evaluate emerging cell and tissue based therapies developed by CTTWA. The EIF program has enabled the implementation of infrastructure to support the development and manufacture of these emerging biotherapies, as well as providing some funding to maintain key staff. CTTWA also receives funding from various funding bodies, including the RPH Medical Research Foundation, to assist in basic research and translational activities.