Cell Therapy for Respiratory Diseases: Optimizing Cell Delivery Strategies

Abstract

Cell therapy is a new research approach being vigorously pursued for the treatment of patients who suffer from many respiratory diseases, ranging from acute respiratory distress syndrome (ARDS), emphysema to idiopathic pulmonary hypertension etc. In such studies, stem cells or progenitor cells are administered with the goal to regenerate damaged pulmonary tissues and to improve their functions. Various adult and embryo derived stem cells are being employed for such investigations. However, as the first crucial step for this approach to be successful, cell delivery methods need to be optimized such that the cells can not only reach the target organs but also can be retained in sufficient quantities.The optimal strategy for cell delivery will depend on the anatomical and functional characteristics of the target organs. For example, for solid organs such as the brain (e.g. for Parkinson's disease) or the heart (for myocardial infarction), direct injection of the cells is being employed, although for the latter, powerful myocardial contractions could cause massive mechanical cell loss from the cell implant sites. For the islet cell transplants (for diabetes), intrahepatic implantation via portal vein appears convenient and effective. As the lung is neither a solid nor an endocrine organ, cell delivery via vascular route appears mandatory.It is now well established that many marrow derived stem / progenitor cells, such as the endothelial progenitor cells (EPCs), are capable of homing in to the tissues suffering from acute injuries (e.g. the lung with ARDS). The roles of inflammatory cytokines and endothelial adhesion molecules for such homing mechanism are being elucidated. Thus for patients suffering from acute lung injuries, intravenous administration of donor cells could be an effective method of cell delivery. However, in patients with chronic conditions such as emphysema, pulmonary fibrosis or hypertension, intravascular delivery of cells results in minimal cell retention, as the donor cells will pass through the pulmonary circulation readily.In this review, we will examine a number of respiratory diseases for which stem cell therapy is being studied, then focusing on the strategies to enable the "trapping" of donor cells administered into the pulmonary circulation in lungs without acute injuries. They may include the pre-treatment of the pulmonary capillary endothelium to induce the expression of adhesion molecules, and more recently the use of innovatively engineered biodegradable microcapsules which can enhance intravascular cell retention and survival. Successful strategies to deliver donor cells to the lung will enable us to rigorously examine the efficacy of cell therapy, thus potentially benefit vast population of patients who suffer wide varieties of respiratory diseases.