Advances in Stem Cell Treatments

Stem cells have the potential to transform medicine by serving as a replacement source for diseased cells. In 2019, HSCI researchers made strides toward bringing cell therapies to patients by focusing on specific conditions such as diabetes and vision loss, and toward preventing the immune rejection of transplanted cells.

Refining cell therapy for diabetes

Clusters of cells derived from stem cells, enriched for insulin-producing beta cells.

In 2014, Douglas Melton, Ph.D. showed for the first time that stem cells could be converted to mature, functional beta cells in the lab, a major step toward giving diabetes patients their own source of insulin. In 2019, Melton developed a way to improve the conversion process, significantly boosting the yield of insulin-producing beta cells.

HSCI researchers analyzed beta cells using single-cell sequencing, and identified a protein expressed uniquely by those cells. By targeting the protein and adding a physical enrichment method developed by collaborators at Semma Therapeutics, the researchers improved the purity of beta cells from 30% to 80%.

With improved control over the beta cell production process, researchers can refine cell therapy for patients with type 1 diabetes. The work is being further developed towards clinical applications at Vertex Pharmaceuticals, which acquired Semma in 2019.

Bioengineering improvements for bone marrow transplants

A bioengineered, injectable sponge improves immune response after a bone marrow transplant.

Bone marrow transplants are a life-saving treatment for a range of blood cancers and diseases, but many transplants fail due to rejection by the patient’s immune system. One way to mitigate rejection is to augment bone marrow transplants with mesenchymal stromal cells (MSCs), which have the capability to help reduce the immune system’s negative effects.

HSCI researchers David Mooney, Ph.D. and David Scadden, M.D. developed an improved method to deliver MSCs and enhance their effectiveness. They took a bioengineering approach to the problem, coating individual MSCs with a thin layer of hydrogel. The coating protected the cells from being cleared by the body, and improved the success of bone marrow transplants in mice.

In a separate study, the same team addressed a different problem: profound, long-term, immune deficiency experienced by patients after bone marrow transplantation. To protect transplanted cells, patients undergo chemotherapy and radiation to suppress their immune cell production. This compromises the patient’s ability to generate immune cells long after treatment. Mooney and Scadden developed an injectable, sponge-like gel that enhances the production of T-cells after a bone marrow transplant. This bioengineered device, which can be injected under the skin, helps revive the immune system after bone marrow transplantation by increasing the quantity and diversity of immune cells.

A clinical trial for restoring vision

As the eye’s outer layer of protection, the cornea needs to constantly regenerate to maintain a clear surface. Vision loss can occur when cornea-regenerating stem cells are damaged due to injury or genetic disease. Natasha Frank, M.D. and Markus Frank, M.D. developed a therapy to replace cornea-generating stem cells and restore vision — and in 2019, they tested it in a patient for the first time.

The researchers identified a molecule on the surface of cornea-regenerating stem cells that can be used to purify the cells. HSCI supported this work during its early, high-risk stage, before the clinical significance of the cell-surface molecule was understood. In the ongoing clinical trial, the treatment process involves taking donor eye tissue, purifying the stem cells, and transplanting the cells to patients with stem cell deficiency.

Cell therapies for any patient, any disease

Organ transplants are sometimes rejected by the patient’s immune system, a situation that can also happen with transplanted cells derived from stem cells. Innovations by HSCI researchers are now enabling a biotechnology company to develop a solution that may work in cell therapies for any patient with any disease.

With funding from HSCI, Chad Cowan, Ph.D. developed methods for making stem cells that are genetically engineered to hide from the immune system. The cells’ genomes are modified to reduce the activity of genes that produce the proteins that can provoke the transplant recipient’s immune system, and to increase the activity of genes that produce molecules that signal “friend,” not “foe.” The modified cells can then be converted into any cell type and transplanted into a patient.

In 2019, Cowan co-founded the start-up Sana Biotechnology. The company is commercializing the HSCI innovations, with the potential to improve cell therapies for many conditions.