HOXB4 But Not BMP4 Confers Self-Renewal Properties to ES-Derived Hematopoietic Progenitor Cells

• DOI: 10.1097/tp.0b013e31818fe741
• Publication Date: 2008-12-15T08:19:57Z
• Authors: Sabrina Bonde; Amy M. Dowden; Kun-Ming Chan; William B. Tabayo...; Nicholas Zavazava
• Keywords: Chimera (genetics)

Achieving transplantation tolerance remains an unresolved clinical challenge. Although bone marrow (BMT) induces mixed chimerism that establishes tolerance, the preconditioning regimens required for BMT to succeed are too prohibitive routine use. Recently, embryonic stem (ES) cells have emerged as a potential alternative cell source cells. However, it difficult efficiently differentiate these into hematopoietic Here, we tested whether morphogenetic protein-4 (BMP-4)-treated or HOXB4-transduced ES-derived engraft permanently inducing long-term chimerism.Initially, 129 SvJ R1 ES (H-2) were treated with BMP-4 36 hr. The phenotyped and polymerase chain reaction studies performed. robustness of was using lymphocyte cultures skin grafts. Chimeric MRL animals received grafts from 129SvJ (H-2), Balb/c class II donor mice, graft survival monitored. Additionally, shown more progenitor engrafted in allogenic syngeneic recipient mice.BMP-4 treatment induced Sca-1 expression up-regulated HOXB4, BMP-4, BMP receptor gene expressions. transient chimerism, whereas derived long term (>100 days).Although promotes hematopoiesis cells, its impact is only transient, permanent ectopic HOXB4 significantly confers self-renewal engraftment This strategy could facilitate establishment induce tolerance.