Exciting Technologies and Ethical Applications
By David Prentice, PhD | November 09, 2017
by David Prentice, PhD
Some scientists have said one reason they don’t consult bioethicists or think about the ethical implications of their research is because ethicists usually say “no” to new technologies, or that ethics is arbitrary. But what they are really avoiding is the necessity of setting rational limits on science, thinking they can thereby avoid any limits on their work. Limits that protect all human beings, even nascent human life, are not arbitrary and actually say “yes” to some exciting—and ethical—applications of new technologies.
Adult stem cell research is one of those areas that emphatically says “yes” to new technology. While often derided as insufficient by those who promote embryo-destructive research, adult stem cells already have a proven track record of success. They can be obtained without harm to the donor (unlike embryonic stem cells or fetal tissue which rely on destruction of the donor) and are the true gold standard of stem cells when it comes to development of successful therapies for patients. Cutting-edge research that can and does lead to new treatments for previously-intractable conditions is a hallmark of adult stem cell studies.
Numerous recent publications highlight the potential of adult stem cell biotechnology for patients. Laboratory production of blood and blood products is one example. One team took mature vascular endothelial cells from mice and turned them into immature hematopoietic stem cells by transient expression of four transcription-factor genes. The new, immature cells were then grown on a layer of human umbilical vein endothelial cells, which secreted various growth factors that stimulated the maturation of the cells into large numbers of fully mature hematopoietic stem cells. When injected into mice, these mature stem cells could colonize bone marrow, proliferate and produce all of the normal blood cells and products seen with native bone marrow stem cells. The newly-formed stem cells could also serve as donor cells in bone marrow transplantations. This lab technique for production of blood stem cells holds great potential for producing new blood for transfusions, and even necessary immune cells for affected patients unable to produce sufficient immune cells of their own.
Another research group developed what they termed an “artificial thymic organoid” or “thymus in a dish” to school immature T-lymphocytes in developing the cellular pathways that enable them to respond to specific antigens in cell-based immunity. They started by creating their own mouse thymic cells by adding a human gene (delta-like canonical Notch ligand 1, DLL1), producing a protein signal that stimulates signaling pathways responsible for some of the T cell maturation in the normal thymus. Additions such as vitamin C to the culture media and co-culture with human hematopoietic stem cells resulted in a 3-dimensional organoid. This artificial thymus was able to produce mature CD8 and CD4 T cells that were virtually indistinguishable from native T cells in the body. The artificial thymic organoids were also able to produce mature T cells, whether starting with cells from umbilical cord blood, adult bone marrow, mobilized peripheral blood or unstimulated peripheral blood. This new system could be useful both in the laboratory as well as for clinical applications.
A just-released report shows precisely how saying “yes” to ethically-directed research can lead to a life-saving treatment. Dr. Michele De Luca at the University of Modena and Reggio Emilia in Italy worked for years to develop ways to grow skin from epidermal adult stem cells taken directly from patients, replacing disease-causing genes to grow healthy skin in the laboratory. Dr. De Luca and his team have now used his techniques of truly effective stem cell therapy to save the life of a young boy in Germany with the often-fatal genetic condition junctional epidermolysis bullosa. The genetic mutation in the boy’s cells caused his skin to lose integrity and fall off rather than to stick together. Dr. De Luca took a tiny patch of skin from the boy, isolated the epidermal stem cells and corrected the genetic problem in stem cell culture. Then they grew patches of genetically-corrected skin and transplanted onto the boy. Reports called the boy’s recovery “stunning” with successful replacement of skin covering more than 80 percent of his body. Within six months of taking the small skin sample, the boy was back in school and has not had even a blister since. The skin has remained healthy, as has the boy, for 21 months at this point, and he loves to show off his “new skin.” In the process, much has been learned about how to move therapies from the lab to the clinic, about the growth of skin stem cells and use of genetic tools to correct human mutations.
All done without destroying or manufacturing a single human embryo, and resulting in a life saved and the promise of more to come.
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