Biomedical Engineers Grow Functioning Human Muscle From Stem Cells

 

From skin cells that have returned to their primordial stem cell state, Duke engineers have grown the first functioning human muscle. Scientists will be able to grow significantly more muscle cells using non-muscle tissue as a starting point, facilitate genome editing and cellular therapies, and create customized models of rare muscle diseases for drug discovery and basic biology research. 

From induced pluripotent stem cells, biomedical engineers have produced the first fully functional human skeletal muscle. The new finding builds on research that was published in 2015 by Duke University researchers, who used cells from muscle biopsies to grow the first functioning human muscle tissue. Scientists will be able to grow significantly more muscle cells using non-muscle tissue as a starting point, facilitate genome editing and cellular therapies, and create customized models of rare muscle diseases for drug discovery and basic biology research. 

Nenad B U R S A-C, a Duke University professor of biomedical engineering, stated, "Starting with pluripotent stem cells, which are not muscle cells but can become any cell in our body, enables us to grow an unlimited number of myogenic progenitor cells". These progenitor cells are similar to "satellite cells," which are adult muscle stem cells that can theoretically produce an entire muscle from a single cell. 

B U R S A-C and his team started their previous work with "my oblasts", small samples of human cells taken from muscle biopsies that had already moved past the stem cell stage but had not yet matured into muscle fibers. They multiplied these my-oblasts by many folds before placing them in a three-dimensional scaffold that was filled with a nourishing gel and provided support, allowing them to form human muscle fibers that were aligned and functioning

Instead, the new study's starting point was human-induced pluripotent stem cells. These are cells that have been reprogrammed to return to their primordial state in adult non-muscle tissues like blood or skin. After that, the pluripotent stem cells are grown while being inundated with the molecule Pax7, which tells the cells to start making muscle. 

The cells became very similar to, but not quite as robust as, adult muscle stem cells as they multiplied.  Although previous studies had achieved this, no one has been able to grow these intermediate cells into skeletal muscle that functions. 

Where previous attempts had failed, the Duke researchers achieved success.

L I-E N G J U N R-A O, a postdoctoral researcher in B U R S-A C lab and the study's first author, stated, "To finally produce functioning human muscle from pluripotent stem cells, it has taken years of trial and error, making educated guesses, and taking baby steps". Our distinctive cell culture conditions and three-dimensional matrix enabled cells to grow and develop much more rapidly and for a longer period of time than with the more typical two-dimensional culture methods. 

B U R S-A C and R-A O stopped giving the cells the Pax7 signalling molecule when the cells were well on their way to becoming muscle, and started giving the cells the support and food they needed to fully mature. 

After two to four weeks of 3-D culture, the researchers demonstrate that the resulting muscle cells form muscle fibers that contract and respond to external stimuli like electrical pulses and biochemical signals that mimic neuronal inputs, just like native muscle tissue. They also implanted the newly developed muscle fibers into adult mice, which demonstrated that they could function and survive for at least three weeks while gradually integrating into the native tissue via revascularization. 

However, the resulting muscle is weaker than native muscle and falls short of the muscle grown in a previous study using muscle biopsies. The researchers say that this muscle still has potential that the older, stronger muscle does not, despite this caveat

Compared to the biopsy method, the stem cell method is capable of growing significantly more cells from a smaller starting batch. Now, researchers are starting work on new models of rare muscle diseases and fine-tuning their method for growing stronger muscles. To address specific issues or correct genetic flaws, the method could be used in conjunction with genetic treatments