STEM CELL THERAPY Dr. OlisaelokaEbeogu
Outline • Definition of Terms • Characteristics of Stem Cells • Categories of Stem Cells • Origin of SCT • Strategies for SCT • Application of SCT in medicine • Concerns • Conclusion
Definition of Terms • Definition: A cell with a unique ability to produce unaltered daughter cells ( self renewal) and to generate specialized cell types(potency). • Self renewal can be asymetric or symmetric • Stem cells can be resident stem cells, isolated stem cells or cultured stem cells.
Embryonic stem cells: • Derived from human blastocysts • Somatic cell nuclear transfer (aka therapeutic cloning) can be used to create ES stem lines identical to that of the patient. • Can replicate infinitely without aging or mutation • Can differentiate into many cell types invitro e.g. neurons, blood cells and cardiac cell • The “stem cell” of stem cells.
Embryonic germ cells are derived from primodial germ layers. Capable of forming 3 germ layers. Fate is limited compared to ES cells. Human adult stem cells: • Responsible for growth and repair of tissues. • Certain tissues that have rapid cell turnover have more of it than those with low turnover – neural tissue vshemapoetic cell. • Usually unipotent, bipotent, tripotent, or multipotent
Each has unique profile of CD markers. • Comprises bone marrow and mesenchymal cells. • Induced pluripotent stem cells are adult somatic cells that have been reprogrammed into pluripotent cells by over expression of four transcription factors normally expressed in in pluripotent cells. • Umbilical cord/progenitor cells are widely used and are associated with less incidence of GVHD. Methods for differentiating it into non-hematopoietic cells are lacking.
Mesenchymal stem cells: • No single definitive marker • Have spindle shaped morphology • Possess capacity to differentiate • Ability to repair tissues
Stem cell therapy implies an attempt to restore diseased tissue function by the implantation of stem cells • Cloning is the process of making genetically identical copies of biologic matter. These may include cells, tissues, or entire organism. It is one of the tools used in SCT. Not synonymous with SCT. • Tissue engineering entails seeding of appropriate cells into a 3-D scaffold and culturing in a bioreactor under conditions optimal for cell growth.
History of SCT • In 1968, the first bone marrow transplant was successfully used in treatment of SCID • Since the 1970’s, bone marrow transplants have been used for treatment of immunodeficiencies and leukemias • 1954 – John Enders received a Nobel prize in Medicine for growing polio virus in human embryonic kidney cells
In 1998, James Thomson (University of Wisconsin-Madison) isolated cells from the inner cell mass of the early embryo, and developed the first human embryonic stem cell lines. • In 1998, John Gearhart (Johns Hopkins University) derived human embryonic germ cells from cells in fetal gonadal tissue (primordial germ cells). • Pluripotent stem cell “lines” were developed from both sources
MODALITIES for SCT • Direct administration of stem cells: This may involve either direct injection into diseased tissue or systemically • Transplantation of differentiated cells derived from stem cells. • Stimulation of endogenous stem cells to facilitate repair. • Stem cells are also excellent candidates as vehicles for gene therapy.
Application of SCT • Replaceable tissues/organs • Repair of defective cell types • Delivery of genetic therapies • Delivery chemotherapeutic agents
Disease Specific Application of SCT • Type 1 diabetes mellitus. • Neurological disease e.gParkinsonsdxs, Alzheimers, stroke, MS, trauma • Immune deficiencies – SCID, Wiskott-Aldrich syndrome, SLE, AIDS. • Skeletal disorders – Osteogenesisimperfecta, chondrodysplasia.
Concerns • Ethical/ religious issues • When does human life begin? • Dr. Alfred Bongioanni (University of Pennsylvania): “I have learned from my earliest medical education that human life begins at the time of conception.” • Dr. Jerome LeJeune (University of Descartes): “after fertilization has taken place a new human being has come into being.”
Concerns • Zygotes are the only source of stem cells • Does life begins from the zygote? • Embryo possesses the full human genome. • Is capable of developing into a complete human being • Is sentient • Possesses cognitive abilities • It therefore has full human right equivalent to that of a child
Some proponents of SCR argue that • Tissues lack “natural potentiality” ( even though they may differentiate into adults). • Newborns lack the ability to perform personal functions – in fact, newborn humans are less capable physically and mentally than virtually all other mammals • Therefore, on the basis of functionally-defined personhood, newborns fail the test could be killed on the basis of “non-personhood.
Other concerns • Funding? • Tumorigenesis? Some ESC have been found to develop into teratomas when they have not differentiated terminally prior to transfer into tissues.
CONCLUSION • Stem cell therapy is an evolving branch of molecular medicine that holds some prospects for ameliorating the effects of terminal illnesses. Research is currently ongoing to perfect the rather less-than-satisfactory results and the greatest hindrance to its this are concerns bothering on ethics and funding.