Genetically engineered adenovirus improves stem cell transplantation

Researchers have discovered that by utilizing a genetically engineered adenovirus they can temporarily stop hematopoietic stem cells from dying, which could lead to more effective transplantation therapy.

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Research lead by scientists from the University of Freiburg (Freiburg, Germany) has found that by using genetically engineered adenoviruses to temporarily inhibit apoptosis of hematopoietic stem cells (HSCs), transplantation therapy can be made more effective. The research was recently published in The Journal of Experimental Medicine.

HSCs are transplanted into patients to treat a number of diseases. The transplantation process is stressful for the HSCs, with a high number dying before they become established. This high mortality rate limits the effectiveness of HSC transplantation.

HSCs die through a process called apoptosis, which is caused by two proteins called BIM and BMF. If BIM and BMF are permanently inhibited, this can lead to further complication including autoimmune disease and lymphomas due to the HSCs not dying at the correct time.  

"Thus, inhibiting apoptosis transiently during the stressful period of transplantation could be an attractive strategy to improve transplantation outcome without increasing the risk of long-term adverse effects," commented study author Miriam Erlacher (University of Freiburg)

Researchers developed a genetically engineered adenovirus that transiently produces a human protein called BCL-XL, which inhibits BIM and BMF. When HSCs from a murine model were transfected with the genetically engineered adenovirus and then transplanted into another murine model, they showed resistance to apoptosis for 7-9 days and had greatly increased efficiency.

"Our findings suggest that transiently inhibiting apoptosis by manipulating donor HSCs increases the fitness of these cells without elevating the risk of adverse pathology," concluded Erlacher. "Transient apoptosis inhibition is therefore a promising approach to reduce the risk of graft failure and improve HSC transplantation outcomes."

Sources: Kollek M, Voigt G, Molnar C et al. Transient apoptosis inhibition in donor stem cells improves hematopoietic stem cell transplantation. J. Exp. Med. doi: 10.1084/jem.20161721.(2017) (Epub ahead of print);


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