Maintaining haematopoietic stem cell (HSC) functionality and efficacy outside the human body is a challenge. So much of a challenge, that Professor Elisa Laurenti of the Cambridge Stem Cell Institute calls it “a major roadblock in guaranteeing HSC gene therapy safety and outcomes.”
Professor Laurenti has been working on a European Research Council (ERC) funded project for the past 18 months, aimed at addressing this roadblock holding back HSC-based gene therapies from their full potential.
Understanding why HSCs lose their function and engraftment potential during in vitro culture could help develop new methodologies to enhance and maintain HSC identity during laboratory manipulation. Ultimately, this could help these kind of cell therapies produce better outcomes for patients.
In August this year, early results from Laurenti’s work were published in the journal Blood, showing that the loss of HSC function in vitro is surprisingly not dependent on the cell cycle, and that targeting the first 24 hours of HSC culture outside the body may be the key to maintaining a therapeutic phenotype. Laurenti’s team identified one early target – JAK/STAT signalling – and showed that JAK inhibitor ruxolitinib could improve HSC function during these crucial first hours.
Now, Laurenti’s team have partnered with Anthony Nolan: Cell Therapy and Laboratory Services to provide them with a steady supply of CD34+ HSCs from mobilised adult peripheral blood in order to continue this project.
Laurenti hopes to find more targets to improve HSC function in vitro during this early adaptation phase, using methods including single cell sequencing to fully characterise the mechanisms of HSC adaption to in vitro culture.
“We're thrilled to be partnering with Anthony Nolan’s Cell Therapy and Laboratory Services on the next phase of this project. Thanks to their expertise and high-quality cellular starting material we can now work with stem cells from mobilized peripheral blood, the same source that is used for current gene therapies. This collaboration opens new doors for us to research how we can enhance stem cell function in clinical protocols and ultimately deliver the highest quality stem cells to patients in greater numbers.”
Professor Elisa Laurenti
Working with our Cell Therapy & Lab Services team not only provides you with access to a range of cellular starting materials, but a whole suite of services including our expert advice and consultancy in product development, regulatory adherence, and genetic sequencing.
We are the only UK stem cell register to liaise directly with transplant centres, meaning that we have unparalleled clinical understanding of the current application of haematopoietic cell therapies.