Progress in tissue engineering consists of many small technology demonstrations similar to the one noted here. Researchers establish that a specific source of cells can be used with a specific recipe for culture and growth in order to generate organoids of a specific tissue type. Given success there as a starting point, further progress becomes possible towards a better quality of structured tissue, and all of the other line items needed on the way to the mass production of patient-matched tissues for use in clinical medicine.
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 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.
"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. These progenitor cells resemble adult muscle stem cells called 'satellite cells' that can theoretically grow an entire muscle starting from a single cell." Induced pluripotent stem cells 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.
"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. 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, the researchers stopped providing the Pax7 signaling molecule and started giving the cells the support and nourishment they needed to fully mature. 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.
The researchers 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. 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 2015 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 earlier biopsy method.