Luis A Ortiz

My interest encompasses all aspects of the academic life including patient care, research, education, and University services. My NIH sponsored research focuses on mechanisms that mediate the development of fibrotic lung disease. In particular, my laboratory has contributed to this field with the development of mouse models of pulmonary fibrosis and the concept that bone marrow derived mesenchymal stem cells (MSCs) are fundamental contributors to the repair of the injured lung. Our research initiatives identified the capacity of MSCs to home to the injured lung and regulate innate immunity by producing the anti-inflammatory cytokine IL1 Receptor antagonist. We are currently exploring the clinical use of MSC derived extracellular vesicles to protect right ventricular function during pulmonary hypertension in lung fibrosis.

My patient care activities are intimately related to my basic science research and concentrate in the management (including lung transplantation) of patients afflicted with acute lung injury (ALI) and Interstitial Lung Disease (ILD). I conduct these activities at the Simmons’ Center for ILD at the Division of Pulmonary Medicine at the University of Pittsburgh. The center, which is the result of a generous gift from the Simmons Family, provides me, as a founding member, with a well-staffed infrastructure where I exert my leadership in research on lung inflammation and fibrosis, into promoting the translation of my basic science discoveries to new treatments for patients with these lung disorders. Consequently, my current clinical efforts are oriented at translating the safety and efficacy of MSCs in patients experiencing ALI or subjects afflicted by idiopathic pulmonary fibrosis (IPF) whose course is complicated by arterial hypertension and right ventricular dysfunction and for whom lung transplantation is not an option.

My research focuses on mechanisms of lung injury that lead to the development of lung fibrosis. In particular, my laboratory has contributed to this field with the development of mouse models of pulmonary fibrosis (silica and bleomycin) and most recently with the concept that bone marrow derived Mesenchymal stem cells (MSCs) are fundamental contributors to the repair of the injured lung. Similarly, my laboratory has characterized the epidemiology of environmentally induced lung disease. Since my arrival to Pittsburgh, I established alliances with grass root organizations to initiate registries and form cohort of subjects exposed to dust (mostly miners) to characterize the impact of pneumoconiosis in the communities of Western Pennsylvania. Subsequently, I contributed to the literature with studies of the prevalence and outcome of silica exposed individuals, and their response to lung transplantation.

Most recent efforts have concentrated in translating these preclinical observations. To that effect I have interacted with Dr. Michael Matthay, an eminent clinical investigator in the field of acute lung injury, to test the efficacy of MSC in subjects afflicted by Adult Respiratory Distress Syndrome (ARDS). These interactions lead Dr. Matthay to designate the University of Pittsburgh as one of the four sites for his START clinical trial, in which we conducted a phase 2a randomized clinical trial to test the safety of well characterized primary human MSCs, manufactured by Dr. David McKenna at the NHLBI-sponsored PACT program at the University of Minnesota, in subjects with ARDS requiring mechanical ventilation in whom a 40 percent mortality was expected. We reported that the administration of these cells in such population of subjects was safe (PMID:30455077).

Taking advantage of the experienced we gained during the development of the START trial and in response to the NHLBI Early Phase Clinical Trials for Therapeutics and Diagnostics we assembled a multidisciplinary team of researchers from five U.S. academic centers with expertise in MSC biology, translational research, lung disease, epidemiology, Current Good Manufacturing Practice (cGMP) regulations and manufacturing, and human clinical trial designto establish a Progenitor Cell Translational Consortium to test the safety, tolerability, and potential benefit of non-HLA-matched allogeneic bone marrow derived mesenchymal stem cells (MSCs) in subjects afflicted by IPF. The Overall hypothesis to be tested by the consortium is that the repeated intravenous administration (two doses separated by a month) of MSC can be accomplished safely in subjects afflicted by IPF. This intervention will modify the gene expression and inflammatory activity of alveolar macrophages (AM) and epithelial cells in the distal lung, and mononuclear cells in peripheral circulation slowing the rate of decline of the forced vital capacity (FVC) and preventing the development of acute exacerbation in IPF.