Abstract
Critical Challenges: Stem cell therapies are based on a simplistic idea of harvesting stem cells from bone marrow, adipose tissue, or induced pluripotent stem cells and injecting them into tissue that requires regeneration. Such ideas are logical and appealing. The only problem is they do not work very well. Effects of stem cell therapy are modest at best and often neither effective nor long lasting. This is because injected stem cells do not survive long. These cells are taken from their comfortable niches and forced to enter a hostile environment of low oxygen, poor nutrients, attacks by immune cells, and the apoptotic agents of death. Current Research Directions: To reach past this impasse, the emerging trend is genetic modification of stem cells for protection and facilitation. Stem cells can be modified to withstand apoptosis and inflammation and even be activated by low oxygen to switch on protective genes to make them survive longer as grafts. Stem cells can be genetically modified to deliver hormones, growth factors, and homing factors. There are multiple methods for modification from gene signaling, antisense inhibition, microRNAs, and inserting transgene switches. Discussion of Specific Examples: Here we discuss examples of gene modification of stem cells for survival after transplantation, turning cells into insulin-producing cells, cells that could reduce plaque in Alzheimer’s and at the same time repair lost neural tissue. Genetically modified stem cells could be a new step forward in stem cell therapy when designed to improve their utility in treating myocardial ischemia and heart failure, hemophilia, stroke, diabetes type 1, spinal cord injury, Alzheimer’s and Parkinson’s diseases, bone defects, and cancer.
Published Version
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