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In vitro Generation of hPSC-derived Functional Skeletal Muscle Tissue



Review of “Engineering human pluripotent stem cells into a functional skeletal muscle tissue” from Nature Communications by Stuart P. Atkinson

The in vitro generation of skeletal muscle tissue from human pluripotent stem cells (hiPSCs) may provide researchers with a means to undertake fundamental biological analyses and develop new treatment strategies for a range of muscle disorders. While many research groups have taken great strides towards this goal [1-4], studies have yet to report the formation of functional and mature three-dimensional (3D) skeletal muscle tissue. 

However, researchers from the laboratory of Nenad Bursac (Duke University, Durham, NC, USA) have recently described the production and differentiation of induced myogenic progenitor cells (iMPCs) from hPSCs into the first entirely hPSC-derived 3D muscle tissues that survive, vascularize, and maintain function following transplantation [5].

Following the generation of iMPCs by induced Pax7 overexpression in hPSC-derived mesoderm cells, Rao et al. employed two-dimensional (2D) conditions to generate a monolayer culture containing two essential components of skeletal muscle tissue: spontaneously contracting multinucleated myotubes and Pax7 expressing muscle stem cell-like cells. However, a shift to optimized 3D conditions (by embedding iMPCs in a fibrin-based hydrogel) promoted the formation of skeletal muscle tissue that displayed higher functionality and more advanced signs of maturity when compared to iMPCs differentiated under 2D conditions. Furthermore, the transplantation and subsequent engraftment of 3D-cultured skeletal muscle tissue into the endogenous muscles of immunocompromised mice led to high levels of vascularization and maintained muscle functionality.

The authors highlight the successful application of both induced pluripotent stem cells and embryonic stem cells for this first example of the in vitro formation of functional and mature skeletal muscle tissue, thereby also establishing the potential for patient-specificity in disease modeling, drug development, and possible muscle repair.

For more on hPSC-derived tissues and their potential, stay tuned to the Stem Cells Portal.


  1. Darabi R, Arpke RW, Irion S, et al., Human ES- and iPS-derived myogenic progenitors restore DYSTROPHIN and improve contractility upon transplantation in dystrophic mice. Cell Stem Cell 2012;10:610-9.
  2. Tedesco FS, Gerli MF, Perani L, et al., Transplantation of genetically corrected human iPSC-derived progenitors in mice with limb-girdle muscular dystrophy. Sci Transl Med 2012;4:140ra89.
  3. Goudenege S, Lebel C, Huot NB, et al., Myoblasts derived from normal hESCs and dystrophic hiPSCs efficiently fuse with existing muscle fibers following transplantation. Mol Ther 2012;20:2153-67.
  4. Choi IY, Lim H, Estrellas K, et al., Concordant but Varied Phenotypes among Duchenne Muscular Dystrophy Patient-Specific Myoblasts Derived using a Human iPSC-Based Model. Cell Rep 2016;15:2301-2312.
  5. Rao L, Qian Y, Khodabukus A, et al., Engineering human pluripotent stem cells into a functional skeletal muscle tissue. Nat Commun 2018;9:126.