Potential of Umbilical Cord Blood Stem Cells in Regenerative Medicine
27 Jun, 2007 06:08 pm
Stem cells have the potential to become all the cells and tissues in the human body. These cells have been described as embryonic stem cells (ESCs) and adult stem cells. ESCs are derived from a very early stage of embryonic development and have proven an invaluable source of knowledge and insight into how primitive progenitor cells can grow in an unrestricted manner and maintain the ability to differentiate into any cell in the body. Adult stem cells arise from many sources such as bone marrow and umbilical cord blood as well as within a wide variety of tissues and organs. These cells typically have less ability to grow indefinitely without differentiating. These adult stem cells are postulated to participate in normal maintenance and repair of adult organisms and perhaps underlie the responses to injuries or diseases that constantly threaten a body during life. When the insult is beyond the ability of the body?s stem cells to thwart the problem, sickness and disease emerge.
We recently reported in the journal Cell Proliferation that a small population of cells from the umbilical cord blood lacked all the typical lineage markers and expressed many markers considered to define the most primitive cells with the greatest potential, ESCs. This observation stimulated us to think that our cord blood stem cells might have the functional potential to become the three developmental lineages (mesoderm, ectoderm, and endoderm) that give rise to all the cells, tissues, and organs in the entire body. Indeed, we showed this potential did exist in our stem cells. We next considered whether these cells had the potential to be engineered into insulin-producing cells, the first step toward production of functional equivalents of beta cells. Our more recent publication in Cell Proliferation describes our studies toward this goal. We showed that several primitive lineages of cord blood-derived stem cells could be engineered to produce insulin. Demonstration of this potential convinced us that the cells contained the requisite program to become beta cell-like. This discovery, although years away from real-life clinical application, was a major step forward towards a cure for type 1 diabetes.
In response to this discovery, we have now turned our attention to another key step in the overall process: growing large numbers of these cells. This is a substantial challenge because most, if not all, adult stem cells have undergone some amount of pre-programming or differentiation that limits their potential to divide by a process of self-renewal without differentiating. Large-scale expansion requires stimulation of growth while suppressing differentiation. Toward this end, we are now studying the molecular mechanisms of growth control in primitive umbilical cord blood stem cells. If we can determine how to grow large numbers of these cells, we already know how to differentiate them so we will be poised to make a huge next step.
Denner L., et al, Directed engineering of umbilical cord blood stem cells to produce C-peptide and insulin, Cell Proliferation 40 (3), June 2007.