Scientists to develop stem cell therapies to treat blood disorders

Scientists and transplant clinicians at the Ansary Stem Cell Institute at Weill Cornell Medical College and the Center for Cell Engineering at Memorial Sloan Kettering Cancer Center have been awarded a $15.7 million, four-year research grant from the New York State Stem Cell Science Program (NYSTEM).

The scientists will translate their approach to manipulate haematopoietic stem cells to cure acquired and inherited blood disorders.

For many patients with such blood diseases, including sickle cell disease, the only hope for a cure requires transplanting normal blood stem cells.

But in many instances suitable blood stem cells cannot be found or there are too few cells for transplantation. The consortium of scientists seeks to expand production of stem cells outside the body using specialised blood vessel cells – known as a vascular niche – to nurture the stem cells.

The scientists will conduct two clinical trials using this platform to expand hematopoietic stem cells.

The first trial uses the vascular niche to expand umbilical cord blood stem cells for transplantation in patients with blood cancers who cannot be cured by chemotherapy or donors.

The second trial aims to correct the genetic abnormality in blood stem cells from patients with sickle cell anemia and return these healthy, functioning stem cells to patients. If successful, the techniques may provide safer, broadly available stem cell transplants to thousands of patients.

''This innovative approach marries Weill Cornell Medical College's stem cell expansion capabilities with Memorial Sloan Kettering's robust cell engineering and gene-transfer techniques,'' says Dr. Shahin Rafii, principal investigator, director of the Ansary Stem Cell Institute and a Weill Cornell professor of medicine, genetic medicine and reproductive medicine.

''We are indebted to our NYSTEM partners for their support, because this award offers the opportunity for new curative therapies for patients with blood malignancies and sickle cell disease,'' says Dr Joseph Scandura, co-principal investigator and a haematopoietic stem cell physician-scientist and scientific director of Weill Cornell's Dr. Richard T. Silver, Myeloproliferative Neoplasm Center.

Scandura is also an assistant professor of clinical medicine at Weill Cornell.

Sickle cell disease is caused by a mutation in the oxygen-carrying protein haemoglobin that distorts the size and shape of red blood cells, causing them to clump together and stick to blood vessel walls, cutting off blood and oxygen supply to vital organs.

There are no FDA-approved techniques to expand blood-forming stem cells to cure this disease, and any patients who do not receive transplants of normal blood stem cells risks life-threatening complications.

''The expansion of blood-forming stem cells is a critical advance for the successful implementation of a number of genetic therapies based on gene addition or gene correction,'' says Dr. Michel Sadelain, principal investigator at Memorial Sloan Kettering (MSK). ''Our combined expertise in stem cell expansion and globin gene therapy for thalassemia is a strong foundation for developing a potentially curative therapy for sickle cell disease,'' he said, referring to a blood disorder in which the body makes an abnormal hemoglobin.

Consortium scientists expect the vascular niche platform will generate large numbers of patients' own blood-forming stem cells, enabling a genetic modification of their stem cells and avoiding the risks of transplanting cells from another person. These two trials will require manufacturing clinical grade human blood vessel, or endothelial cells, for intravenous infusion for clinical trials.

The NYSTEM grant supports a collaborative effort led by Rafii and Scandura at the Ansary Stem Cell Institute at Weill Cornell and Sadelain and Dr. Isabelle Rivière at MSK. Their team brings significant expertise with stem-cell engineering and clinical translation of cell therapies. Phase I clinical trials are expected to start within the next two to three years.