Acute Lung Injury is a serious complication of several clinical disorders including severe pneumonia and other infections. The mechanism for development of this syndrome includes damage to the lung air and blood barriers resulting in accumulation of fluid within the lungs – so called “drowning on the ground”. Patients cannot absorb sufficient oxygen from air, which can lead to respiratory failure and death.
There is a major pressing medical need for a new treatment of patients with Acute Lung Injury, a syndrome that has a high mortality rate (40%) and affects 200,000 patients annually in the US. Currently, the only treatment is supportive care with lung protective mechanical ventilation. There is compelling experimental and preclinical evidence that adult human mesenchymal stem cells and their secreted products have a high likelihood of being effective in the treatment of Acute Lung Injury in humans.
The studies that we propose in this application will advance the field of intensive care medicine and treatment of severely ill patients. The objective of the proposed research is to develop a Target Product for Therapy of Acute Lung Injury based upon the concept that the human stem cells produce large quantities of biologically active substances with therapeutic potential. Balanced array of biologically active substances from stem cells facilitates regeneration of injured tissue. Compared to adult human stem cells from the bone marrow which are mostly used currently, human placental cells possess higher therapeutic potential for treatment because of their more primitive nature, higher activity, better growth characteristics, cost and availability.
We will demonstrate the potential of placental stem cells and their products to facilitate repair of injured lung. We will characterize the composition of biologically active substances in products of placental stem cells. First, we will investigate importance of multiple major growth factors and anti-inflammatory proteins in the mechanisms of action by gene silencing. Second, we will determine the effects of specific or non-specific cell stimulation on release of biologically active substances by cells to determine ways to facilitate these effects.
We will develop a therapeutic product and demonstrate its effectiveness when delivered to the lungs as an aerosol. Use of cell products instead of live stem cells allows easier production and delivery, standard development, excludes tumor development and adverse immune reactions. The Target Product will be tested in animals and human lungs.
Stem cell-based therapies are the promising future of medicine. The application of this treatment is limited because of the restricted supply of effective and appropriate stem cell lines, as it is necessary to match certain characteristics of the donor’s and host’s immune systems.
Acute Lung Injury affects approximately 20,000-30,000 California residents, and 40% of these patients do not survive. Our pioneering studies demonstrated that human placenta may be used as a source of mesenchymal stem cell lines for the treatment of ALI. These cell lines derived from human placenta will contribute to clinical applications. Our hypothesis is that the tissue of human term placenta is a high capacity source of primitive stem cells capable of improving outcomes in patients with ALI. Other diseases that can potentially be cured by the use of stem cell treatment afflict significant number of individuals in California.
These stem cell lines will be used in regenerative medicine research and cell replacement therapies as well as the development of new treatment approaches. The enhanced and extended lives of the individuals will represent an evident benefit; the savings to the health care system as a consequence of their cure will straightforwardly benefit all California taxpayers. Ultimately the knowledge and experience produced by the work proposed will contribute to the goal of making stem cell transplantation and new medical approaches available to a much broader group of patients, thus greatly extending the benefits to the affected individuals and to the taxpayers of California.