Lack of self-renewal capacity in Fancc-/- stem cells after ex vivo expansion

¹ Laval University, Québec, Canada
² CHUQ-Hôpital Saint-François d'Assise, Québec, Canada
³ Laval University, CHUQ-Hôpital Saint-François d'Assise, Québec, Canada

^* To whom correspondence should be addressed. E-mail: madeleine.carreau{at}crsfa.ulaval.ca.

	Abstract

Treatments of the hematological manifestation in Fanconi anemia (FA) is first supportive with attempts to stimulate hematopoiesis with androgens or hematopoietic growth factors. However, the long-term curative treatment of the hematological manifestation in Fanconi anemia patients is bone marrow (BM) or cord blood stem cell transplantation. The success rate for BM transplantation is fairly high with HLA-matched sibling donors but is, unfortunately, low with HLA-matched unrelated donors. An alternative curative treatment for those patients with no sibling donors might be gene transfer into hematopoietic stem cells. Since FA patients have reduced numbers of stem/progenitor cells, ex vivo expansion of hematopoietic stem cells would be a crucial step in gene transfer protocols. Using the Fanconi anemia mouse model, Fancc^-/-, we tested the ability of CD34^- hematopoietic stem cells to support ex vivo expansion. We determined that Fancc^-/- CD34^- stem cells have reduced reconstitution ability and markedly reduced self-renewal ability following culture as shown by secondary transplants. These results indicate that FA stem cells may not be well suited for ex vivo expansion prior to gene transfer or transplantation protocols.