Regenerative Medicine Comes of Age

Two distinguished UT Southwestern scientists discuss new developments in regenerative medicine.

Regenerative medicine offers the potential to heal or replace tissues damaged by age, disease, or trauma, as well as to cure congenital diseases. It encompasses numerous strategies – many of which are being employed by UT Southwestern Medical Center scientists, among whom are some of the top researchers in the field.

A prime example is Sean Morrison, Ph.D., founding Director of the Children’s Medical Center Research Institute (CRI) at UT Southwestern, who is leading a team performing innovative research aimed at understanding mechanisms that maintain stem cell function in adult tissues and the ways in which cancer cells hijack these mechanisms to enable tumor formation.

“We study the regulation of stem cell function – and the role that stem cells play in regenerating adult tissues,” Dr. Morrison says. “Our focus is on the bone marrow, where two important types of stem cells are found: hematopoietic and mesenchymal stem cells.”

Focusing In on Stem Cells

Recent research by Dr. Morrison and his colleagues provided new insights into the ability of specialized cells in the bone marrow to regulate hematopoiesis and osteogenesis, including the roles of endothelial cells and leptin receptor-expressing mesenchymal stromal cells.

Dr. Morrison further explains that his laboratory found that leptin receptor-expressing stromal cells serve three crucial functions in stem cell biology. These cells are the main source of growth factors required for the maintenance of hematopoietic stem cells, serve as precursors to osteoblast cells needed for bone growth, and produce bone-forming growth factors required to maintain skeletal bone mass.

“We recently discovered a new bone-forming growth factor that has the potential to reverse bone loss associated with osteoporosis,” Dr. Morrison says.

The researchers named the new bone-forming growth factor Osteolectin, which is produced by the leptin receptor-expressing cells in the bone marrow. Dr. Morrison and his team at CRI were the first to demonstrate that Osteolectin promotes new bone formation by stimulating the formation of osteoblasts from the leptin receptor expressing skeletal stem cells.

“The identification of Osteolectin is just one example of the highly innovative work at UT Southwestern that is creating new opportunities for tissue regeneration therapies,” he adds.

Heralding Advances in Cardiac Medicine

Another prominent UT Southwestern scientist working in regenerative medicine is Eric Olson, Ph.D., Professor and founding Chair of the Department of Molecular Biology and Director of the Hamon Center for Regenerative Science and Medicine. His research seeks to understand how stem cells adopt specific fates and how programs of cell differentiation and morphogenesis are controlled during muscle development.

“We’re working to decipher the genetic networks that direct the formation of muscle tissues during development,” Dr. Olson says.

We recently discovered a new bone-forming growth factor that has the potential to reverse bone loss associated with osteoporosis.

“Our current focus is on the development of gene therapies that could provide solutions for treating heart disease where traditional therapies have failed,” Dr. Olson says.

In collaboration with the Christine Seidman, M.D., Lab at Harvard Medical School, Dr. Olson and his team recently showed that CRISPR–Cas9 base editing and prime editing can be harnessed to correct genetic and acquired models of cardiac disease in mice and human cells. Dr. Olson notes that this is an important milestone for the application of gene therapy to treating heart failure.

“Technical proof of concept has now been established for how to treat cardiomyopathies caused by mutations in the MYH7 and the RBM20 genes,” Dr. Olson says. “The first gene therapies for tackling heart failure are making progress toward the clinic.”

The Olson Lab is studying how stem cells adopt specific fates and how programs of cell differentiation and morphogenesis are controlled during muscle development. The current focus is the development of gene therapies that could provide solutions for treating heart disease when traditional therapies have failed.

Future Directions

Drs. Morrison and Olson anticipate that many gene correction treatment approaches will eventually be implemented into clinical practice. However, they note that these approaches are still in the preclinical stage and that much effort is ongoing at UT Southwestern and elsewhere to realize their lifesaving potential.

Sean Morrison, Ph.D., is Professor and founding Director of the Children’s Medical Center Research Institute at UT Southwestern and a Howard Hughes Medical Institute Investigator. His laboratory studies the mechanisms that maintain adult tissues and how cancer cells hijack these mechanisms.

Eric Olson, Ph.D., is Professor and founding Chair of the Department of Molecular Biology. He directs the Hamon Center for Regenerative Science and Medicine and co-directs the Wellstone Muscular Dystrophy Cooperative Research Center. He studies muscle regeneration.