Stem Cells - Cell Therapy and Regenerative Medicine

Stem Cells

Stem cell research is advancing at a rapid pace and is the subject of significant scientific, ethical, and political discussion (Ho and Gibaldi, 2003). A timely, informative discussion of totipotent and pluripotent stem cells, and their potential for repair of tissues and organs is well beyond the scope of this chapter. For general information about stem cells, the reader is encouraged to research the topic in any biology textbook and a plethora of websites. Specialized stem cell topics can be studied using readily available online databases (journal and abstract) and website search engines. The U.S. National Institutes of Health (NIH) has a valuable resource on stem cells that can be found at www.nih.gov/news/stemcell/index.htm. A brief introduction follows solely to provide the reader with insights into the unproven potential of pluripotent stem cell research in advancing tissue engineering capabilities.

During normal human development, a single cell is produced from the joining of a sperm cell and an egg cell (please see source for this introduction at NIH StemCell Primer, www.nih.gov/news/stemcell/primer.htm).This single cell, capable of forming an entire human, initially undergoes division into two identical daughter cells. These are totipotent cells. Each totipotent cell has the capability to differentiate into the embryo, extra-embryonic membranes and tissues, and all postembryo-nic tissues and organs. Placing one of the identical cells (or both for identical twins) in a woman’s uterus has the potential to develop into a fetus. Several cycles of cell division cause the beginning of cell specialization and the formation of a blastocyst, a hollow sphere of cells. The placenta and other supporting tissues needed for fetal development in the uterus is formed from the outer layer of cells of the blastocyst while the inner cell layer can become virtually every cell type found in the human body; “virtually” every cell type. The inner cell mass is pluripotent, that is, they are capable of giving rise to many types of cells, but not all cells and not an embryo. Their potential is not total (totipotent). Further cell divisions and specializations result in cells that are committed to give rise to cells that perform specialized functions. These multipotent stem cells are extremely important to the process of cell proliferation and differentiation occurring during early human develop-ment. Types are also found in children and adults. They may be multipotent or pluripotent.

Stem cells are cells that possess the ability to divide into daughter cells and multiply for infiniteperiods in culture giving rise to daughter cells with identical developmental potential and/or a cell with less potential. A totipotent stem cell can give rise to daughter totipotent stem cells and/or pluripotent stem cells. Likewise, a pluripotent stem cell can give rise to daughter pluripotent stem cells and/or multi-potent stem cells, etc. For example, hematopoietic stem cells are multi-potent stem cells that give rise to multipotent hematopoietic stem cells and/or white blood cells, red blood cells and platelets. Cord (blood) stem cells are found in umbilical cords (multipotent mesenchymal stem cells) at birth. Adult stem cells are present in some fully formed organs (such as bone marrow, brain, and skin) in which they produce new cells that are damaged and/ or destroyed. Therefore, pluripotent stem cells are of real potential value to tissue engineering and regen-erative medicine because of their pluripotent capabilities.

Fundamental discoveries remain to be made before this bench top research can be translated into bedside clinical medicine. Results from the first controlled human cell therapy trials for heart disease are now in (Chien, 2006; Shaw, 2006). The Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute myocardial Infarction (REPAIR-AMI) trial studied direct intracoronary infusion of bone marrow progenitor cells in patients who had successful acute MI therapy. Small, but statistically significant im-provement to left ventricular ejection fraction (5.5% vs. 3% LVEF) was observed in a double-blinded trial in those patients who received bone marrow stem cells. However, results have been mixed. Another trial attempted to repopulate injured myocardium with autologous skeletal muscle myoblasts to achieve cardiac muscle regeneration. The trial was terminated due to a lack of sufficient therapeutic effect. Spinal cord injury, stroke, diabetes, depression, autism, sickle cell anemia, Parkinson’s, muscular dystrophy, ALS, and aging are all potential targets for cell therapy (Enserink, 2006; Madsen and Serup, 2006; Everts, 2007). Predicting what the future of cell therapy and stem cell research will hold is fraught with risk. However, biotechnology has experienced exponential advances in capabilities since the first edition of this text was written. If the natural requisite growth factors and appropriate differentiation/proliferation conditions can be identified and mimicked reprodu-cibly, tissue engineering with pluripotent stem cells may give rise to repairing virtually all cells, tissues and organs including bone marrow, nerve cells, heart muscle, breast replacements, pancreatic islet cells, skin, a liver, etc. Researchers are also attempting to determine if there are conditions in which multipotent stem cells that are already more differentiated and committed to particular cell types can be converted to pluripotent capabilities.