Muscle Development & Regeneration

Building “mini muscles” from stem cells

by Heather Buschman, Ph.D. on March 20, 2013 at 8:48 am | 0 Comments

Skeletal myospheres ("mini muscles") generated by adding MyoD and BAF60C to embryonic stem cells

To make “mini muscles” from stem cells, you need the protein BAF60C.

Pier Lorenzo Puri, Ph.D., and his team study what makes a muscle cell just that—a muscle cell. They’re especially interested in applying that information to regenerate new muscle for people with muscular dystrophy.

Last year, the team discovered that two proteins called MyoD and BAF60C work together to mark the DNA of precursor cells, setting them on a course to become muscle cells. When the MyoD/BAF60c complex receives the right signals, it unwinds the cell’s genome and begins the process of producing muscle-specific proteins. This chain of events eventually triggers these precursor cells—those that hang out in our normal muscle tissue—to mature into new muscle cells.

“Junk DNA” drives embryonic development

by Heather Buschman, Ph.D. on December 3, 2012 at 6:04 am | 0 Comments

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Differentiating mouse embryonic stem cells (green = mesoderm progenitor cells, red = endoderm progenitor cells). The microRNAs identified in this study block endoderm formation, while enhancing mesoderm formation.

An embryo is an amazing thing. From just one initial cell, an entire living, breathing body emerges, full of working cells and organs. It comes as no surprise that embryonic development is a very carefully orchestrated process—everything has to fall into the right place at the right time. Developmental and cell biologists study this very thing, unraveling the molecular cues that determine how we become human.

“One of the first, and arguably most important, steps in development is the allocation of cells into three germ layers—ectoderm, mesoderm, and endoderm—that give rise to all tissues and organs in the body,” explains Mark Mercola, Ph.D., professor and director of Sanford-Burnham’s Muscle Development and Regeneration Program in the Sanford Children’s Health Research Center.

In a study published November 14 in the journal Genes & Development, Mercola and his team, including postdoctoral researcher Alexandre Colas, Ph.D., and Wesley McKeithan, discovered that microRNAs play an important role in this cell- and germ layer-directing process during development.

Stem cells 101

by Communications Staff on October 8, 2012 at 10:52 am | 2 Comments

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Sanford-Burnham's Stem Cell Research Center

Congratulations to John B. Gurdon and Shinya Yamanaka on winning the 2012 Nobel Prize in Physiology or Medicine! They received the award today for their “discovery that mature cells can be reprogrammed to become pluripotent.” In other words, these scientists figured out how to turn a normal adult cell, such as a skin cell, into a stem cell that has the potential to become any other type of cell in the body. Read below to learn more about stem cells and how they are revolutionizing medical research.

What are stem cells?

Stem cells are special because each is like a blank slate. Once it’s given the proper instruction, a stem cell can specialize and become any type of cell in the body—brain, heart, muscle, and more. Stem cells also have the ability to reproduce themselves indefinitely, renewing the supply.

Are there different types of stem cells?

Embryonic stem cells only exist during an organism’s development, when it is an embryo. These cells are pluripotent, meaning they have the capacity to become any cell type in the body.

Adult stem cells exist in fully developed organisms. They are more limited than embryonic stem cells—they are multipotent rather than pluripotent. These stem cells usually can only become a few types of specialized cells, based on the tissue from which they originate.

Induced pluripotent stem cells (iPSCs) are pluripotent, much like embryonic stem cells. iPSCs are produced in the laboratory by genetically reprogramming any adult cell, such as a skin cell.

Mending a broken heart—with a molecule that turns stem cells into heart cells

by Heather Buschman, Ph.D. on August 2, 2012 at 9:01 am | 1 comment

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Stem cell-derived cardiomyocytes (heart muscle cells) expressing a green fluorescent protein

For years, scientists have been looking for a good source of heart cells that can be used to study cardiac function in the lab, or perhaps even to replace diseased or damaged tissue in heart disease patients. To do this, many are looking to stem cells. Researchers at Sanford-Burnham Medical Research Institute, the Human BioMolecular Research Institute, and ChemRegen, Inc. have been searching for molecules that convert stem cells to heart cells for about eight years—and now they’ve found one. Writing in the August 3 issue of Cell Stem Cell, the team describes how they sifted through a large collection of drug-like chemicals and uncovered ITD-1, a molecule that can be used to generate unlimited numbers of new heart cells from stem cells.

“Heart disease is the leading cause of death in this country. Because we can’t replace lost cardiac muscle, the condition irreversibly leads to a decline in heart function and ultimately death. The only way to effectively replace lost heart muscle cells—called cardiomyocytes—is to transplant the entire heart,” said Mark Mercola, Ph.D., director of Sanford-Burnham’s Muscle Development and Regeneration Program and senior author of the study. “Using a drug to create new heart muscle from stem cells would be far more appealing than heart transplantation.”

Meet 7 trail-blazing female scientists

by Heather Buschman, Ph.D. on July 9, 2012 at 12:28 pm | 0 Comments

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Dr. Alessandra Sacco

Can you name a present-day female scientist? If not, check out today’s issue of U-T San Diego to meet seven female scientists blazing new trails in San Diego, including our own Dr. Alessandra Sacco:

New muscle research center opens in San Diego

by Heather Buschman, Ph.D. on January 27, 2012 at 6:23 am | 0 Comments

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The new San Diego Skeletal Muscle Research Center will be made up of three core facilities shared by five local institutions.

The National Institutes of Health (NIH) recently awarded a new grant to establish the San Diego Skeletal Muscle Research Center. This new center, led by UC San Diego’s Rick Lieber, Ph.D., Sanford-Burnham’s Mark Mercola, Ph.D., and The Scripps Research Institute’s Velia Fowler, Ph.D., will allow 21 scientists at five different research institutions to combine their expertise and state-of-the-art methods to accelerate research that advances our understanding of skeletal muscles and the diseases that affect them.

Muscling up with MyoD

by Faculty Contributor on January 13, 2012 at 8:49 am | 1 comment

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Lorenzo Puri, M.D., Ph.D.

Every cell in your body contains the same DNA, with genes coding for many thousands of proteins. Yet a muscle cell makes a very different set of proteins from say, a bone cell, enabling it to perform its muscle-specific job. Lorenzo Puri, M.D., Ph.D. and his lab members study what makes stem cells (precursor cells) choose to produce the proteins that turn them into muscle cells. In doing so, they hope their research will one day help improve strategies for muscle regeneration in patients with muscle wasting diseases, such as muscular dystrophy. While a cure for muscular dystrophy is not yet in sight, the ability to stimulate muscle stem cells to generate mature muscle cells could make a big difference in the lives of patients. By repairing muscles damaged by the disease, muscle regeneration therapy would extend the lives of patients and allow them to function effectively in a whole range of activities that are currently unthinkable for victims of the disease.

A few minutes with Mark Mercola

by Josh Baxt on May 2, 2011 at 12:00 pm | 2 Comments

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Dr. Mark Mercola

Dr. Mark Mercola directs Sanford-Burnham’s Muscle Development and Regeneration Program and is looking for ways to regenerate damaged heart tissue. He is particularly interested in growing cardiomyocytes (beating heart cells) from stem cells and finding ways to spur a person’s existing heart precursor cells, which can already heal small injuries, to work harder to tackle major heart disease.

On June 20-21, 2011, Dr. Mercola is chairing a conference on Cardiomyocyte Regeneration and Protection. Sponsored by Abcam, the conference will combine basic and clinical research findings to move us closer to new treatments. Recently, Dr. Mercola talked to Abcam about the upcoming conference…

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Leaders among peers

by Heather Buschman, Ph.D. on April 29, 2011 at 9:32 am | 0 Comments

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Sanford-Burnham scientists are leading several exciting symposia over the next few months. Please follow the links below for more event and registration information.

2011 Signaling, Metabolism and Hypoxia Symposium
Chaired by Dr. Ze’ev Ronai
May 6, 2011, 2:00 – 5:30 p.m. (PDT)
Sanford-Burnham Medical Research Institute
10901 North Torrey Pines Road
La Jolla, California

2011 Glycobiology Gordon Research Conference
Chaired by Dr. Hudson Freeze
May 8 – 13, 2011
Il Ciocco Hotel
Lucca (Barga), Italy

Sanford-Burnham’s 33rd Annual Symposium: Structural Systems Biology
Chaired by members of the Bioinformatics and Systems Biology Program
Drs. Adam Godzik, Dorit Hanein, Andrei Osterman, Niels Volkmann
June 7, 2011, 9:00 a.m. – 5:15 p.m. (PDT)
Hilton La Jolla Torrey Pines
La Jolla, California

Cardiomyocyte Regeneration and Protection
Chaired by Dr. Mark Mercola
Sponsored by Abcam
June 20 – 21, 2011
Hilton La Jolla Torrey Pines
La Jolla, California

2011 Molecular Therapeutics of Cancer Research Conference
Chaired by Dr. Sara Courtneidge
Sponsored by the Cancer Molecular Therapeutics Research Association
July 10 – 14, 2011
Asilomar Conference Center
Pacific Grove, California

Seventh General Meeting of the International Proteolysis Society
Chaired by Dr. Guy Salvesen and Dr. Matthew Bogyo
October 16 – 20, 2011
Hilton San Diego Resort and Spa
San Diego, California

Personalized Medicine 101

by Amelia Tomas on April 21, 2011 at 3:54 pm | 1 comment

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Dr. Steven Smith, Scientific Director for the Florida Hospital Sanford-Burnham Translational Research Institute, demonstrates sophisticated equipment used in metabolic studies.

Dr. Steven Smith, Scientific Director for the Florida Hospital Sanford-Burnham Translational Research Institute, cares for a patient.

In 2003, the completion of the human genome project gave us an unprecedented amount of genetic information. From this, a new clinical concept is emerging: personalized medicine.

Conventional medical care generalizes treatment to all patients with a particular disease. But since a disease is as individual as the person who has it, casting a wide therapeutic net has its limitations. For one, patients with a certain genetic makeup might not respond to a particular drug as well as patients with different genetics, or they might experience different side effects. As personalized medicine becomes a reality, it could rectify these less-than-ideal situations.

From the diagnostic point-of-view, personalized medicine is a shift from reactive to proactive. Based on a person’s health, genetic, and environmental profiles, doctors practicing personalized medicine could assess a patient’s risk for acquiring a genetic disease before any symptoms develop. This might allow them to target the specific genes that account for illness (the BRCA1/BRCA2 genes that predispose a woman to breast cancer, for example), incorporate a prevention strategy, and monitor those genes over time. When it comes to treatment, personalized drugs could be prescribed based on an individual’s molecular “build” and targeting treatment where it will do the most good and the least harm.

New mouse model for muscular dystrophy

by Heather Buschman, Ph.D. on December 9, 2010 at 9:37 am | 1 comment

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Dr. Alessandra Sacco

Roughly 50,000 people in the United States are affected by some type of muscular dystrophy, a condition characterized by debilitating muscle loss. Duchenne muscular dystrophy (DMD), the most common form of the disease, is caused by a mutation in the dystrophin gene. Without dystrophin, the interior muscle fiber frame can’t properly connect to the surrounding environment. Despite this knowledge, lack of a good DMD model has long hampered scientists in their efforts to study the disease and develop new therapies. Although the current DMD mouse model replicates the dystrophin gene mutation seen in humans, the mice don’t suffer the same devastating symptoms. Writing December 9 in the journal Cell, researchers in Dr. Helen Blau’s group at Stanford University, including Drs. Alessandra Sacco, Foteini Mourkioti and Jason Pomerantz, uncover the molecular reason for this model’s shortcomings, and use that information to create a more accurate mouse model for DMD.

Dr. Sacco, now assistant professor at Sanford-Burnham, notes the importance of this new mouse model. “There are no effective cures for DMD. Several therapies seemed promising after they cured muscular defects in mice, but they failed in human clinical trials. Our new model will provide a more precise tool for studying muscular dystrophy and testing new therapies.”

Putting the muscle in muscle stem cells

by Heather Buschman, Ph.D. on October 8, 2010 at 8:09 am | 65 Comments

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Patients with muscular dystrophy suffer debilitating muscle loss that gets worse as they age. As the disease progresses, resident stem cells in a patient’s muscle tissue have to work extra hard trying to replace the diseased muscle. Over time, this special population of stem cells gets exhausted as they constantly proliferate (make more stem cells) and differentiate (specialize into new muscle cells).

Dr. Pier Lorenzo Puri, associate professor at Sanford-Burnham and Italy’s Dulbecco Telethon Institute, and colleagues are figuring out ways to keep the muscle stem cell pool fresh and ready to regenerate injured or diseased muscle. In a study published today in the journal Cell Stem Cell, they uncover the molecular messengers that translate inflammatory signals into the genetic changes that tell muscle stem cells to differentiate. These findings give the scientists a target to artificially dial the stem cell population up or down, a potential treatment that could boost muscle regeneration in muscular dystrophy patients.

“Our mission is to improve the lives of these patients and extend their lives until they can benefit from a cure 20 years from now,” says Dr. Puri, a medical doctor who has worked with many muscular dystrophy patients throughout his career.

Top Stories - Muscle Development & Regeneration

Building “mini muscles” from stem cells

“Junk DNA” drives embryonic development

Stem cells 101

What are stem cells?

Are there different types of stem cells?

Read More

Mending a broken heart—with a molecule that turns stem cells into heart cells

Meet 7 trail-blazing female scientists

New muscle research center opens in San Diego

Muscling up with MyoD

A few minutes with Mark Mercola

Leaders among peers

Personalized Medicine 101

New mouse model for muscular dystrophy

Putting the muscle in muscle stem cells

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