Nav: Home

Engineers grow functioning human muscle from skin cells

January 09, 2018

DURHAM, N.C. -- Biomedical engineers have grown the first functioning human skeletal muscle from induced pluripotent stem cells.

The advance builds on work published in 2015 when researchers at Duke University grew the first functioning human muscle tissue from cells obtained from muscle biopsies. The ability to start from cellular scratch using non-muscle tissue will allow scientists to grow far more muscle cells, provide an easier path to genome editing and cellular therapies, and develop individually tailored models of rare muscle diseases for drug discovery and basic biology studies.

The results appear online Tuesday, January 9, in Nature Communications.

"Starting with pluripotent stem cells that are not muscle cells, but can become all existing cells in our body, allows us to grow an unlimited number of myogenic progenitor cells," said Nenad Bursac, professor of biomedical engineering at Duke University. "These progenitor cells resemble adult muscle stem cells called 'satellite cells' that can theoretically grow an entire muscle starting from a single cell."

In their previous work, Bursac and his team started with small samples of human cells obtained from muscle biopsies, called "myoblasts," that had already progressed beyond the stem cell stage but hadn't yet become mature muscle fibers. They grew these myoblasts by many folds and then put them into a supportive 3-D scaffolding filled with a nourishing gel that allowed them to form aligned and functioning human muscle fibers.

In the new study, the researchers instead started with human induced pluripotent stem cells. These are cells taken from adult non-muscle tissues, such as skin or blood, and reprogrammed to revert to a primordial state. The pluripotent stem cells are then grown while being flooded with a molecule called Pax7 -- which signals the cells to start becoming muscle.

As the cells proliferated they became very similar to --but not quite as robust as -- adult muscle stem cells. While previous studies had accomplished this feat, nobody has been able to then grow these intermediate cells into functioning skeletal muscle.

The Duke researchers succeeded where previous attempts had failed.

"It's taken years of trial and error, making educated guesses and taking baby steps to finally produce functioning human muscle from pluripotent stem cells," said Lingjun Rao, a postdoctoral researcher in Bursac's laboratory and first author of the study. "What made the difference are our unique cell culture conditions and 3-D matrix, which allowed cells to grow and develop much faster and longer than the 2-D culture approaches that are more typically used."

Once the cells were well on their way to becoming muscle, Bursac and Rao stopped providing the Pax7 signaling molecule and started giving the cells the support and nourishment they needed to fully mature.

In the study, the researchers show that after two to four weeks of 3-D culture, the resulting muscle cells form muscle fibers that contract and react to external stimuli such as electrical pulses and biochemical signals mimicking neuronal inputs just like native muscle tissue. They also implanted the newly grown muscle fibers into adult mice and showed that they survive and function for at least three weeks while progressively integrating into the native tissue through vascularization.

The resulting muscle, however, is not as strong as native muscle tissue, and also falls short of the muscle grown in the previous study that started from muscle biopsies. Despite this caveat, the researchers say this muscle still holds potential that the stronger, older relative does not.

The pluripotent stem cell-derived muscle fibers develop reservoirs of "satellite-like cells" that are necessary for normal adult muscles to repair damage, while the muscle from the previous study had much fewer of these cells. The stem cell method is also capable of growing many more cells from a smaller starting batch than the biopsy method.

Both of the advantages point toward a possibility of using this new method for regenerative therapies and for creating models of rare diseases for future studies and individualized health care.

"The prospect of studying rare diseases is especially exciting for us," said Bursac. "When a child's muscles are already withering away from something like Duchenne muscular dystrophy, it would not be ethical to take muscle samples from them and do further damage. But with this technique, we can just take a small sample of non-muscle tissue, like skin or blood, revert the obtained cells to a pluripotent state, and eventually grow an endless amount of functioning muscle fibers to test."

The technique also holds promise for being combined with genetic therapies. Researchers could, in theory, fix genetic malfunctions in the induced pluripotent stem cells derived from a patient and then grow small patches of completely healthy muscle. While this could not heal or replace an entire body's worth of diseased muscle, it could be used in tandem with more widely targeted genetic therapies or to heal more localized problems.

The researchers are now refining their technique to grow more robust muscles and beginning work to develop new models of rare muscle diseases.
-end-
This work was supported by National Institutes of Health (UH3-TR000505, UG3-TR002142, AR065873, and AR070543).

CITATION: "Engineering Human Pluripotent Stem Cells Into a Functional Skeletal Muscle Tissue." Lingjun Rao, Ying Qian, Alastair Khodabukus, Thomas Ribar and Nenad Bursac. Nature Communications, January 2018. DOI: 10.1038/s41467-017-02636-4

Duke University

Related Pluripotent Stem Cells Articles:

A new method for creating safer induced pluripotent stem cells
Induced pluripotent stem cells (IPSCs) hold great promise in regenerative medicine, personalized medicine and drug discovery.
Approaching a decades-old goal: Making blood stem cells from patients' own cells
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
Boston University scientists turn human induced pluripotent stem cells into lung cells
Boston University scientists have announced two major findings that further our understanding of how stem cells become organs: the ability to grow and purify the earliest lung progenitors that emerge from human stem cells, and the ability to differentiate these cells into tiny 'bronchospheres' that model cystic fibrosis.
Findings: Induced pluripotent stem cells don't increase genetic mutations
Despite immense promise, adoption of induced pluripotent stem cells (iPSCs) in biomedical research and medicine has been slowed by concerns that these cells are prone to increased numbers of genetic mutations.
Scientists take aging cardiac stem cells out of semiretirement to improve stem cell therapy
With age, the chromosomes of our cardiac stem cells compress as they move into a state of safe, semiretirement.
Purest yet liver-like cells generated from induced pluripotent stem cells
A team of researchers from the Medical University of South Carolina and elsewhere has found a better way to purify liver cells made from induced pluripotent stem cells.
Stem cell scientists discover genetic switch to increase supply of stem cells from cord blood
International stem cell scientists, co-led in Canada by Dr. John Dick and in the Netherlands by Dr.
Modeling NAFLD with human pluripotent stem cell derived immature hepatocyte like cells
Researchers from the Institute for Stem Cell Research and Regenerative Medicine at the University Clinic of Düsseldorf have established an in vitro model system for investigating nonalcoholic fatty liver disease (NAFLD).
Non-healing tissue from diabetic foot ulcers reprogrammed as pluripotent stem cells
Researchers at Tufts University School of Dental Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts, led by Jonathan Garlick, have established for the first time that skin cells from diabetic foot ulcers can be reprogrammed to acquire properties of embryonic-like cells.
Study sets standards for evaluating pluripotent stem cell quality
As the promise of using regenerative stem cell therapies draws closer, a consortium of biomedical scientists reports about 30 percent of induced pluripotent stem cells they analyzed from 10 research institutions were genetically unstable and not safe for clinical use.

Related Pluripotent Stem Cells Reading:

Atlas of Human Pluripotent Stem Cells in Culture
by Lyn Healy (Author), Ludmila Ruban (Author)

This lavishly-illustrated, authoritative atlas explores the intricate art of culturing human pluripotent stem cells. Twelve chapters – containing more than 280 color illustrations – cover a variety of topics in pluripotent stem cell culturing including mouse and human fibroblasts, human embryonic stem cells and induced pluripotent stem cells, characteristic staining patterns, and abnormal cultures, among others. Atlas of Human Pluripotent Stem Cells in Culture is a comprehensive collection of illustrated techniques complemented by informative and educational captions examining... View Details


The Science of Stem Cells
by Jonathan M. W. Slack (Author)

Introduces all of the essential cell biology and developmental biology background for the study of stem cells 

This book gives you all the important information you need to become a stem cell scientist. It covers the characterization of cells, genetic techniques for modifying cells and organisms, tissue culture technology, transplantation immunology, properties of pluripotent and tissue specific stem cells and, in particular, the relevant aspects of mammalian developmental biology. It dispels many misconceptions about stem cells—especially that they can be miracle... View Details


Induced Pluripotent Stem (iPS) Cells: Methods and Protocols (Methods in Molecular Biology)
by Kursad Turksen (Editor), Andras Nagy (Editor)

This volume aims to be a collection of essential protocols in iPS cell field. Induced Pluripotent Stem (iPS) Cells: Methods and Protocols guides readers through multiple facets of stem cell biology, lineage commitment and differentiation. Written for the Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls.

Authoritative and practical, Induced... View Details


Patient-Specific Induced Pluripotent Stem Cell Models: Generation and Characterization (Methods in Molecular Biology)
by Andras Nagy (Editor), Kursad Turksen (Editor)

This volume captures the rapid developments in the field of induced pluripotent stem (iPS) cells, which have provided novel opportunities and approaches both for better understanding a number of human diseases and for developing new platforms for drug development and screening for such diseases. Specifically, representative protocols on various disease models have been collected from labs around the world. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents,... View Details


Stem Cell Banking: Concepts and Protocols (Methods in Molecular Biology)
by Jeremy M. Crook (Editor), Tenneille E. Ludwig (Editor)

This volume covers protocols related to both pluripotent and somatic stem cells, including the ethical procurement of tissues and cells for the provision of “seed stock,” standardized methods for deriving hESCs and iPSCs, isolating mesenchymal stem cells, cell culture and cryopreservation, in addition to quality assurance and information management. Stem Cell Banking: Concepts and Protocols aims to contribute to the development of this field by providing information that is essential to establishing a bona fide stem cell bank. Written in the highly successful Methods in... View Details


Chapter 31, Inducible Pluripotent Stem Cells In Autism Spectrum Disorders
by Academic Press

NOTE: This is a single chapter excerpted from the book The Neuroscience of Autism Spectrum Disorders, made available for individual purchase. Additional chapters, as well as the entire book, may be purchased separately.


Autism is no longer considered a rare disease, and the Center for Disease Control now estimates that upwards of 730,000 children in the US struggle with this isolating brain disorder.  New research is leading to greater understanding of and ability to treat the disorder at an earlier age.  It is hoped that further genetic and imaging studies will... View Details


Thomas' Hematopoietic Cell Transplantation, 2 Volume Set: Stem Cell Transplantation
by Stephen J. Forman (Editor), Robert S. Negrin (Editor), Joseph H. Antin (Editor), Frederick R. Appelbaum (Editor)

Fully revised for the fifth edition, this outstanding reference on bone marrow transplantation is an essential, field-leading resource. Extensive coverage of the field, from the scientific basis for stem-cell transplantation to the future direction of research Combines the knowledge and expertise of over 170 international specialists across 106 chapters Includes new chapters addressing basic science experiments in stem-cell biology, immunology, and tolerance Contains expanded content on the benefits and challenges of transplantation, and analysis of the impact of new therapies to help... View Details


Stem Cells: Current Challenges and New Directions (Stem Cell Biology and Regenerative Medicine)
by Kursad Turksen (Editor)

This volume looks at the state-of-the-science in stem cells, discusses the current challenges, and examines the new directions the field is taking. Dr. Turksen, editor-in-chief of the journal "Stem Cell Reviews and Reports," has assembled a volume of internationally-known scientists who cover topics that are both clinically and research-oriented. The contents range from sources of stem cells through their physiological role in health and disease, therapeutic applications in regenerative medicine, and ethics and society. An initial overview and a final summary bookend the contents into a... View Details


Stem Cells and Cancer Stem Cells, Volume 10: Therapeutic Applications in Disease and Injury
by M.A. Hayat (Editor)

Presenting contributions by 66 experts representing 13 countries, Volume 10 of the series Stem Cells and Cancer Stem Cells synthesizes current understanding of the causes, diagnosis, and therapy of major human diseases and debilitating tissue and organ injuries, using cell-based treatment. This volume presents contemporary research into generation, preservation, and uses of stem cells in fighting disease and tissue/organ injuries.

The contents of the volume are organized into five sections. Mesenchymal Stem Cells section includes chapters on the use of stem cells in bone... View Details


Human Pluripotent Stem Cells: A Practical Guide
by Wiley-Blackwell

Comprehensive coverage of the entire induced pluripotent stem cell basic work flow 

Pluripotent stem cells (PSC) can divide indefinitely, self-renew, and can differentiate to functionally reconstitute almost any cell in the normal developmental pathway, given the right conditions. This comprehensive book, which was developed from a training course, covers all of the PSCs (embryonic, embryonic germ, and embryonic carcinoma) and their functions. It demonstrates the feeder-dependent and feeder-free culture of hESC and hiPSC, which will be referred to in all protocols as PSCs.... View Details

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

The Big Five
What are the five biggest global challenges we face right now — and what can we do about them? This hour, TED speakers explore some radical solutions to these enduring problems. Guests include geoengineer Tim Kruger, president of the International Rescue Committee David Miliband, political scientist Ian Bremmer, global data analyst Sarah Menker, and historian Rutger Bregman.
Now Playing: Science for the People

#456 Inside a Conservation NGO
This week we take a close look at conservation NGOS: what they do, how they work, and - most importantly - why we need them. We'll be speaking with Shyla Raghav, the Climate Change Lead at Conservation International, about using strategy and policy to tackle climate change. Then we'll speak with Rebecca Shaw, Lead Scientist at the World Wildlife Fund, about how and why you should get involved with conservation initiatives.