TY - JOUR
T1 - Correction of hemophilia as a proof of concept for treatment of monogenic diseases by fetal spleen transplantation
AU - Aronovich, Anna
AU - Tchorsh, Dalit
AU - Katchman, Helena
AU - Eventov-Friedman, Smadar
AU - Shezen, Elias
AU - Martinowitz, Uri
AU - Blazar, Bruce R.
AU - Cohen, Sivan
AU - Tal, Orna
AU - Reisner, Yair
PY - 2006/12/12
Y1 - 2006/12/12
N2 - Previous clinical attempts to correct genetic deficiencies such as hemophilia or Gaucher disease by transplantation of allogeneic spleen were associated with aggressive graft versus host disease, mediated by mature T cells derived from the donor spleen. We show that a fetal pig spleen harvested at the embryonic day 42 stage, before the appearance of T cells, exhibited optimal growth potential upon transplantation into SCID mice, and the growing tissue expressed factor VIII. Transplantation of embryonic day 42 spleen tissue into hemophilic SCID mice led to complete alleviation of hemophilia within 2-3 months after transplant, as demonstrated by tail bleeding and by assays for factor VIII blood levels. These results provide a proof of principle to the concept that transplantation of a fetal spleen, obtained from a developmental stage before the appearance of T cells, could provide a novel treatment modality for genetic deficiencies of an enzyme or a factor that can be replaced by the growing spleen tissue.
AB - Previous clinical attempts to correct genetic deficiencies such as hemophilia or Gaucher disease by transplantation of allogeneic spleen were associated with aggressive graft versus host disease, mediated by mature T cells derived from the donor spleen. We show that a fetal pig spleen harvested at the embryonic day 42 stage, before the appearance of T cells, exhibited optimal growth potential upon transplantation into SCID mice, and the growing tissue expressed factor VIII. Transplantation of embryonic day 42 spleen tissue into hemophilic SCID mice led to complete alleviation of hemophilia within 2-3 months after transplant, as demonstrated by tail bleeding and by assays for factor VIII blood levels. These results provide a proof of principle to the concept that transplantation of a fetal spleen, obtained from a developmental stage before the appearance of T cells, could provide a novel treatment modality for genetic deficiencies of an enzyme or a factor that can be replaced by the growing spleen tissue.
KW - Embryonic
KW - Factor VIII
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UR - http://www.scopus.com/inward/citedby.url?scp=34247862789&partnerID=8YFLogxK
U2 - 10.1073/pnas.0607012103
DO - 10.1073/pnas.0607012103
M3 - Article
C2 - 17148607
AN - SCOPUS:34247862789
SN - 0027-8424
VL - 103
SP - 19075
EP - 19080
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 50
ER -