In a research published in the New England Journal of Medicine, researcher expressed cautious optimism about efforts to genetically engineer hematopoietic stem cells (HSCs) to temporarily resist cell death during transplantation. While these gene therapy approaches could dramatically improve patient outcomes, their risks must be carefully studied in diverse models.

Stem cell therapies are used for patients who are critically ill or have suppressed immune systems. Derived from bone marrow, peripheral blood or umbilical cord blood, HSCs can be transplanted to treat a variety of cancers, anaemia and other conditions. As a result, developing stronger stem cells could improve care for many patients.

In the study, the researchers had engineered HSCs to transiently resist apoptosis (programmed cell death) resulting in greater engraftment. By helping HSCs manage the stresses associated with transplantation, more of these cells might survive the process, which also has implications to improve outcomes for patients undergoing other types of stem cell therapies.

Impairment of apoptosis brings potential risks. One of a cancer cell's many tricks is evading cell death by altering this same pathway. The current study developed means to allow HSCs to have only a temporary block in the pathway which could enhance the transplant process while minimizing the risks to patients.

Precision medicine is not just better targeting. It is also controlling the targeting so it is not always on or always off. Inducing a transient alteration to the stem cell may be the best approach, said Murphy, UC Davis expert, who has done extensive research on hematopoietic stem cell transplantation.

While the researchers present a promising application for gene therapy, it is important to remember earlier, heart-breaking clinical disasters in which patients died, which delayed these treatments for many years. Rather than risk repeating history, scientists and clinicians must be exceptionally diligent before transplanting engineered HSCs into patients.

The laboratory mouse model cannot provide enough precise data to completely assess potential risks to human patients. If the research would rely on the mouse model, it could underestimate adverse events, so it is needed to push the model to better reflect the human scenario.

HSCs with transiently-impaired cell death mechanisms can provide great benefits for patients, even potentially for organ transplants. The studies are promising, but they need to be more stringently assessed since that is the advantage of the mouse models and to possibly validate them in larger animals, before rushing into the clinic, Murphy concluded.