Regenerative Medicine Archives - Sanford Burnham Prebys
Institute News

Teaching stem cells to build muscle

Authorjmoore
Date

February 18, 2016

Researchers in Alessandra Sacco’s lab have found a key to enhancing repair of damaged muscle. In work published in Cell Reports, they describe why fetal muscle stem cells (MuSCs) are better at regenerating muscle compared to adult MuSCs. The research opens the door for new approaches to treat muscle diseases including muscular dystrophies, which affect approximately 50,000 people in the U.S., and muscle wasting associated with cancer and aging.

“We found that fetal MuSCs remodel their microenvironment by secreting specific proteins, and then examined whether that same microenvironment can encourage adult MuSCs to more efficiently generate new muscle. It does, which means that how adult MuSCs normally support muscle growth is not an intrinsic characteristic, but can be changed,” explained Matthew Tierney, a graduate student at SBP and first author of the study.

The proteins that fetal MuSCs secrete are part of the extracellular matrix (ECM), the meshwork of strand-like proteins and starches that make up the structure of MuSCs’ microenvironment. As fetal MuSCs mature into adult MuSCs, they take on different responsibilities and help change their microenvironment over time to support their distinct functions. Fetal MuSCs are geared toward creating new muscle, whereas adult MuSCs repair damaged muscle and self-replicate to sustain the pool of stem cells to mend future injuries.

In muscular dystrophies and muscle wasting, progressive degeneration overwhelms the regenerative capacity of adult MuSCs. The new study showing that adult MuSCs living in a microenvironment with fetal characteristics are better at regenerating muscle provides rationale for developing drugs that could trigger this transition.

“These results help explain the differences between the capacity of fetal and adult MuSCs to repair muscle. Such an understanding is urgently needed, as no treatments are yet available for muscular dystrophies and muscle-wasting disorders,” stated Alessandra Sacco, PhD, associate professor in the Development, Aging, and Regeneration Program at SBP and senior author of the study.

“Our findings fit with the growing appreciation of the importance of a cell’s structural and biochemical surroundings in influencing cellular behavior. Managing the microenvironment is an emerging approach to treat many diseases, from cancer to cardiovascular disease to neurodegeneration. We’re excited about the implications of our research for treating muscle diseases, and look forward to applying our conclusions toward development of therapies.”

The full text of the paper is available here.

Institute News

Researchers resolve longstanding issue of components needed to regenerate muscle

Authorsgammon
Date

February 9, 2016

Researchers at SBP have conclusively identified the protein complex that controls the genes needed to repair skeletal muscle. The discovery clears up deep-rooted conflicting data and will now help streamline efforts towards boosting stem cell-mediated muscle regeneration. Such strategies could treat muscle degenerative diseases such as muscular dystrophies, and those associated with aging and cancer. Continue reading “Researchers resolve longstanding issue of components needed to regenerate muscle”

Institute News

New Department of Defense grant funds efforts to treat ALS with stem cells

Authorjmoore
Date

January 28, 2016

Evan Snyder, MD, PhD, director of the Center for Stem Cells and Regenerative Medicine and a professor in SBP’s Human Genetics Program, was awarded a grant to develop a stem cell treatment for amyotrophic lateral sclerosis (ALS). ALS, also known as Lou Gehrig’s disease, involves degeneration and death of motor neurons (which control voluntary muscles), causing difficulty speaking, swallowing, and eventually breathing. No available treatments can slow the progression of ALS, which affects approximately 20,000 people in the U.S.

As new therapies are urgently needed, the Department of Defense announced a funding program for new therapeutic ideas in ALS in 2015. Snyder received one of eight grants awarded in this competitive program.

This grant will support research on human neural stem cells (hNSCs) as an approach to support the survival and function of existing motor neurons. The Snyder lab is modifying hNSCs so that they can be administered via the bloodstream and home to the spinal cord. This strategy allows the stem cells to become distributed throughout the spinal cord, overcoming a previous limitation. Snyder’s team has already shown that transplanted NSCs improved motor performance, respiratory function, and symptom-free survival in a mouse model of ALS.

hNSCs are already in phase I clinical trials for ALS, which have shown that this therapy is safe. These trials were possible in part because of the Snyder lab’s pioneering work in preclinical models. The current research promises to lead to an improved version of this therapy.