Idiopathic pulmonary fibrosis (IPF) refers to the scarring of the interstitium – the supporting framework of the lungs as well as the pulmonary tissues, with fibroblast proliferation, deposition of extracellular matrix, and progressing fibrosis of the tissues.

It is a debilitating, lethal condition which progressively worsens, leading to decreasing lung volumes and hypoxemic respiratory failures — and eventually to death if left untreated. The disease has a mean overall survival time of two to three years. From 7 to 16 cases of IPF are reported every year in the U.S. per 100,000 people.

Causes of IPF

The exact causes of IPF are unknown, but past studies have attributed many cases to excessive smoking and exposure to environmental allergens and toxins. It is referred to as “idiopathic” because there are not exact proven causes.

Pathogenesis of IPF

Past studies have traced the development of IPF as a function of repeated damage caused to the alveolar epithelium. Injury causes alveolar epithelial cells to attract fibroblasts, which induce proliferation and differentiation into myofibroblasts and production of extracellular matrix (ECM). The damage caused to the epithelia is not healed properly, and the same process is repeated again, which leads to progressive damage to the lung tissues and its surroundings. As a result, scarring, honeycombing, and fibrosis are more of the effects of improper wound healing than of immunomodulation.

There is evidence of upregulation of genes related to cytokine and chemokine synthesis, and high levels of uric acid secreted during IPF. The main therapeutic focus is to normalize wound healing and re-epithelization of the alveolar lining, along with modulation of key inflammatory pathways.

Treating IPF

Current therapies for treatment of IPF include a combination of immunosuppressants, corticosteroids, anti-oxidants, and anti-fibrotic agents. However, recent studies have shifted the focus toward regenerative medicine for the treatment of this progressive condition.

Stem cell therapy as a possible therapeutic option

Stem cell therapy has been shown to have the ability of regenerating damaged organs and tissues totally or partially, depending on their potential and source of extraction. Totipotent stem cells (TSCs), which are formed during the placental stage of development of newborns within the mother’s womb, are considered to be among the most important stem cells because they have the potential to develop into any cell found in the human body. But there are ethical issues which restrict the extraction of TSCs.

The next in terms of potential are the pleuripotent stem cells (PSCs), which have the ability to regenerate any human tissue or organ. Mesenchymal stem cells (MSCs) are multipotent stem cells which have the ability to form particular tissues (such as bones, nerves, cartilage, and fat cells).

PSCs have demonstrated the ability to develop into pulmonary epithelial and endothelial cells under laboratory conditions in pre-clinical studies and animal models, so they are considered one of the potent contenders for therapeutic intervention.

A clinical study at the Prince Charles Hospital in Brisbane, Australia, is assessing the safety and efficacy of stem cell therapy in eight patients with IPF. The study is in collaboration with the Mater Medical Research Institute, and is led by Dr. Daniel Chambers, M.D. This has led to the inception of human clinical trials with stem cell therapy as a hope for IPF therapy.

A study published several years ago also hinted at the potential of adipose-derived stem cells (ADSC), which have been shown to have an advantage over those derived from umbilical cord or bone marrow in terms of regenerative capabilities, ease of extraction, and ex-vivo expandability.

Intravenous administration of ADSC in mouse models and laboratory-induced IPF models exposed to smoke and allergens has shown that alveolar type II cells can be grown under specific conditions. The suggested protocol for ADSC extraction has been formulated which refers to fat harvesting, stem cell extraction, activation, and delivery into the patient’s system (endobronchial autologous infusion) within two hours. This would eventually increase respiratory and forced volume capacity and contribute to improved lung health.

With lung transplantation currently being the only stable treatment option with a limited success rate, IPF patients and caregivers are hoping for the success of stem cell clinical trials in order to ensure a positive regenerative therapy.