title: Enhancing bone marrow regeneration by SALL4 protein.
abstract: Hematopoietic stem cells (HSCs) are widely used in transplantation therapy to treat a variety of blood diseases. The success of hematopoietic recovery is of high importance and closely related to the patient's morbidity and mortality after Hematopoietic stem cell transplantation (HSCT). We have previously shown that SALL4 is a potent stimulator for the expansion of human hematopoietic stem/progenitor cells in vitro. In these studies, we demonstrated that systemic administration with TAT-SALL4B resulted in expediting auto-reconstitution and inducing a 30-fold expansion of endogenous HSCs/HPCs in mice exposed to a high dose of irradiation. Most importantly, TAT-SALL4B treatment markedly prevented death in mice receiving lethal irradiation. Our studies also showed that TAT-SALL4B treatment was able to enhance both the short-term and long-term engraftment of human cord blood (CB) cells in NOD/SCID mice and the mechanism was likely related to the in vivo expansion of donor cells in a recipient. This robust expansion was required for the association of SALL4B with DNA methyltransferase complex, an epigenetic regulator critical in maintaining HSC pools and in normal lineage progression. Our results may provide a useful strategy to enhance hematopoietic recovery and reconstitution in cord blood transplantation with a recombinant TAT-SALL4B fusion protein.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liao
authors.forename: Jerell R
authors.initials: JR
authors.lastname: Aguila
authors.forename: Yixin
authors.initials: Y
authors.lastname: Yao
authors.forename: Jianchang
authors.initials: J
authors.lastname: Yang
authors.forename: Gary
authors.initials: G
authors.lastname: Zieve
authors.forename: Yongping
authors.initials: Y
authors.lastname: Jiang
authors.forename: Cecilia
authors.initials: C
authors.lastname: Avila
authors.forename: Lisa
authors.initials: L
authors.lastname: Senzel
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
authors.forename: Dazhong
authors.initials: D
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.forename: Yupo
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012038:Regeneration / Q000187:drug effects; D061987:Sf9 Cells; D014157:Transcription Factors / Q000494:pharmacology*
chemical_list: C472575:SALL4 protein, human; D014157:Transcription Factors