Stem cell transplantation: the potential for medicalbreakthroughs in PID treatment Nabila El-Sheikh MIU, Al-Azhar University
Topics covered • Types of SCs • The challenges of human SCs research • Potential uses of SCs in PID treatment
Introduction • There are several specific medical therapies available for patients with PID • Established therapies • Experimental type of therapy
Introduction cont’ • Stem cells come in two general types: • Embryonic stem cells (ESC) • Adult stem cells • Stem cells are characterized by two fundamental properties: • self-renewal and • differentiation capacity
Human ESCs • ESCs can be extracted from very young human embryos -- typically from surplus frozen embryos left over from in-vitro fertilization (IVF) procedures at fertility clinics
Ethical issues • Research on the human embryonicSC has generated much interest & public debate • Pluripotent stem cell lines have been isolated from human embryos that are a few days old, as well as from fetal tissue (older than 8 weeks of development).
Ethical issues • Many pro-lifers believe that human life becomes a human person at the time of fertilization. • Others disagree. They believe that an embryo has the potential to develop into a person, but is not a person itself.
Supported Research • Scientists replaced a specific stretch of DNA in hESC - homologous recombination • Advance: Scientists can now study the function of specific genes within these cells and could modify hESC-derived tissues for potential treatment in patients with PIDD.
Supported Research • Scientists observe that differentiated mESCs repaired damage when transplanted into the mouse brain or spinal cord. • Advance: May lead to development of replacement therapy for cells destroyed by injury or disease, such as stroke, Parkinson’s or Alzheimer’s disease.
Supported Research Advance: In vitro studies produced cells from hESC that might be used for blood cell transplantation therapies for patients with blood malignancies such as leukemia or myeloma.
Supported Research • Scientists identified genes that are involved in the differentiation of hESCs and genes that permit ESCs to self-renew. • Advance: Gene transfer techniques may permit scientists to coax hESCs into becoming specialized cells, eg. insulin-producing beta cells to treat insulin-dependent diabetes.
Supported Research Scientists tested the ability of human feeder cells derived from fetal or adult tissues to support the growth of hESC. Advance: This is an ideal system for identifying factors secreted by human feeder cells that maintain hESCs’ self-renewing and multipotent state.
Supported Research Scientist isolated multipotent adult progenitor cells from human bone marrow Advance: Adult SCs demonstrated the potential to differentiate beyond bone marrow SCs and into other cell types, including liver cells, neurons and blood vessel-forming cells.
Supported Research • Scientists demonstrated that umbilical cord SCs are able to repopulate the bone marrow of a small child, but only a small number of cells are obtained from each umbilical cord. • Advance: Scientists are now seeking methods to expand cells in culture to generate larger numbers for use in clinical applications.
Hematopoietic stem cell transplantion • The stem cells that give rise to the lymphocytes and other cells of the immune system, also make blood cells. They are called “Hematopoietic” stem cells (HSC). • The process of taking stem cells from one person and putting them into another is therefore called “HSCT”.
HSCT in PIDD • HSCT is most often used to treat severe combined immune deficiency (SCID) • HSCT has also been used in some patients to treat other PIDD such as the Wiskott-Aldrich syndrome, hyper-IgM syndromes, and CGD
Potential obstacles • Graft Rejection • Failure of engraftment • GvHD
Selection of the Donor • A “matched” HSCT is one that uses a donor whose transplantation antigens are very similar or identical to those of the recipient. • There are alternative methods for giving transplants to patients who do not have a matched donor in their own family
Concluding Remarks • BMT between HLA matched siblings has been successfully employed in the treatment of PID since 1968. • The chances of a successful transplant in SCID with full recovery by the recipient will be best if the transplant is done within the first month of life.
Patients with CGD, or hyper IgM syndromes who require chemotherapy before the transplant to allow engraftment of the new BM can also be cured by HSCT. • The best survival is in children transplanted under the age of five who are relatively free of infections and who do not have pre-existing lung or liver damage.