Neuromuscular junctions (NMJs) crumble in ALS leading to muscle weakness and paralysis. A growing number of scientists are therefore hoping to identify drugs that stabilize them to help keep muscles moving. However, better protocols may be needed to generate the large number of cells required to create NMJs in vitro for drug discovery purposes.
Now, a research team led by Erasmus University Medical Center’s Pim Pijnappel in the Netherlands reports a transgene-free method to produce skeletal muscle cells from induced pluripotent stem cells (iPSCs) that can be expanded up to 5 × 1011-fold.
The approach comes at the heels of a technique developed by Washington University School of Medicine’s Andrew Yoo in St. Louis, Missouri that enables human motor neurons to be created directly from skin cells – at least from healthy people (see September 2017 news; Abernathy et al., 2017). The strategy is one of a growing number of approaches that aim to streamline the production of these cells to investigate their role in neurodegenerative diseases including ALS and discover potential treatments for them (see September 2017, March 2018 news; Shi et al., 2018).
The protocol is published on May 3 in Stem Cell Reports.
Meanwhile, scientists are developing strategies to recreate NMJs in vitro (see February 2018 news). One strategy, developed by a research team led by University of Central Florida’s J. Hickman, uses a microfluidic system, known as BioMEMs, to help muscles and motor neurons make these connections. The approach creates functional NMJs that can transmit electrical signals, triggering muscle contraction (Santhanam et al., 2018). In future, Hickman’s team, in collaboration with Hesperos in Orlando, Florida, plans to use this approach to identify potential therapies for ALS. Stay tuned.
To find out about drugs in the ALS pipeline that aim to keep muscles and motor neurons connected, check out Meeting At The ALS Junction.
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Santhanam N, Kumanchik L, Guo X, Sommerhage F, Cai Y, Jackson M, Martin C, Saad G, McAleer CW, Wang Y, Lavado A, Long CJ, Hickman JJ. Stem cell derived phenotypic human neuromuscular junction model for dose response evaluation of therapeutics. Biomaterials. 2018 Jun;166:64-78. [PubMed].