Aplastic anemia (AA) is a life-threatening disease of bone marrow in which the destruction of stem cells leads to a failure to produce blood
cells including red cells, bleeding and an inability to fight
infections. In the past, the study of AA has had great impact on medical
progress; including the discovery that bone marrow is a site of blood
cell production, discovery of bone marrow stem cells and application of
bone marrow transplantation. Current treatments including bone marrow
transplantation in AA can be applied and are effective in a proportion
of patients but for many no suitable donors are available. Improvement
of the management of AA is an important goal of medical research in
hematology. In this project, we propose to provide a proof of concept
for the feasibility of clinical application of adult stem cell therapy
inAA.

Our proposal is based on progress made in adult stem cell technologies.
Recently, several laboratories have invented a new method which allows
for a successful reprogramming of mouse and human skin cells into stem
cells, also called induced pluripotent stem cells (iPS). These
genetically engineered stem cells have a potential of revolutionizing
the treatment of many otherwise incurable human diseases; the progress
made using animals and healthy human tissues suggests that the remaining
obstacles will be overcome. Consequently, it is important to identify a
suitable clinical application which could serve as a proof of concept
for the broader application of adult stem cells. We stipulate that AA is
such a model disease as decreased numbers of bone marrow stem cells
provide an opportunity for a cure via simple replacement. We propose
that AA patients in whom medical therapies are ineffective and who lack
a suitable donor could themselves serve as a source of mature cells from
unaffected organs for generation of iPS. Upon genetic reprogramming into
iPS, these autologous cells could be transformed into bone marrow stem
cells, providing the ability to perform transplantation with a patient's
own fully matched bone marrow stem cells. Ultimately, such treatment
could be applied to other patients, voiding the need for matched donors
and alleviating the risk of rejection reactions.