Regenerative Medicine and Idiopathic Pulmonary Fibrosis

There are hundreds of discrete lines of research within the broad field of regenerative medicine; projects that can be divided up by tissue type, organ, and approach to building therapies. The open access paper quoted below can be taken as an example of the complexity of ongoing work on just one age-related disease in one organ. The large scale funding devoted to stem cell medicine starts to look less large when you multiply the amount of work required to make progress here by all of the varied organs and tissues in the body:

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible disease of the lung that has no lasting option for therapy other than transplantation. It is characterized by replacement of the normal lung tissue by fibrotic scarring, honeycombing, and increased levels of myofibroblasts. The underlying causes of IPF are still largely unknown, but this disease preferentially affects adults older than 60 years. The focus of the current review is the possible use of stem cell therapy, specifically mesenchymal stem cells (MSCs), a multipotent stromal cell population, which have demonstrated promising data in multiple animal models of pulmonary fibrosis (PF). The most studied source of MSCs is the bone marrow, although they can be found also in the adipose tissue and umbilical cord, as well as in the placenta. MSCs have immunomodulatory and tissue-protective properties that allow them to manipulate the local environment of the injured tissue, ameliorating the inflammation and promoting repair.

Animal models have shown the success of MSC therapy in mitigating the fibrotic effects of bleomycin-induced PF. However, bleomycin, the most commonly used model for PF, is imperfect in mimicking IPF as it presents in humans, as the duration of the illness is not parallel or reversible, and honeycombing is not produced. Furthermore, the time of MSC dosage has proven to be critical in determining whether the cells will ultimately have a positive or negative effect on disease progression, since it has been demonstrated that the maximal beneficial effect of MSCs occurs during the early inflammatory phase of the disease and that there is no or negative effect during the late fibrotic phase. Therefore, all the current clinical trials of MSCs and IPF, though promising, should proceed with caution as we move toward true stem cell therapy for this disease.

Because IPF primarily affects older patients, the issue of aging is intrinsically linked to many aspects of the disease, including the age of the stem cells. In our opinion, an important weakness in the study of IPF is the lack of knowledge of lung aging, which is a main risk factor in IPF. Until now, most of the mouse models have included young animals (less than 3 months), and it is clear that in humans IPF is a pathology of the elderly, and as the association between aging, IPF, and stem cells is well developed, this variable must be taken into account in evaluating preclinical results and in translation to human applications.


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