English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse
  1. View item / 
  2. Item Summary

Item

ITEM ACTIONSEXPORT
Add to Basket
  Local TagsRelease HistoryDetailsSummary

Released
Journal Article

Transient apoptosis inhibition in donor stem cells improves hematopoietic stem cell transplantation

MPS-Authors
There are no MPG-Authors in the publication available
External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)

jem_20161721.pdf
(Any fulltext), 2MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Kollek, M., Voigt, G., Molnar, C., Murad, F., Bertele, D., Krombholz, C. F., et al. (2017). Transient apoptosis inhibition in donor stem cells improves hematopoietic stem cell transplantation. Journal of experimental medicine: JEM, 214(10), 2967-2983. doi:10.1084/jem.20161721.


Cite as: https://hdl.handle.net/21.11116/0000-000F-1855-7
Abstract
During hematopoietic stem cell transplantation, a substantial number of donor cells are lost because of apoptotic cell death. Transplantation-associated apoptosis is mediated mainly by the proapoptotic BCL-2 family proteins BIM and BMF, and their proapoptotic function is conserved between mouse and human stem and progenitor cells. Permanent inhibition of apoptosis in donor cells caused by the loss of these BH3-only proteins improves transplantation outcome, but recipients might be exposed to increased risk of lymphomagenesis or autoimmunity. Here, we address whether transient inhibition of apoptosis can serve as a safe but efficient alternative to improve the outcome of stem cell transplantation. We show that transient apoptosis inhibition by short-term overexpression of prosurvival BCL-XL, known to block BIM and BMF, is not only sufficient to increase the viability of hematopoietic stem and progenitor cells during engraftment but also improves transplantation outcome without signs of adverse pathologies. Hence, this strategy represents a promising and novel therapeutic approach, particularly under conditions of limited donor stem cell availability.