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New Muscle Stem Cell Expansion Technique May Boost Muscle Regeneration Strategies

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Review of “Selective Expansion of Skeletal Muscle Stem Cells from Bulk Muscle Cells in Soft Three-Dimensional Fibrin Gel” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Studies have indicated that muscle stem cells (MuSCs) possess the potential to repair damaged or diseased muscle; however, the relative scarcity of adult MuSCs residing in muscle tissues currently inhibits any regenerative exploitation. Ex vivo expansion of sorted MuSCs represents one prospective solution, although current sorting steps are expensive, require large amounts of patient-derived cells, and involve the risk of contamination or the loss of regenerative capacity [1]. 

In a new STEM CELLS Translational Medicine study, researchers from the laboratory of Wen-Shu Wu (University of Illinois at Chicago, USA) now describe a soft three-dimensional (3D) fibrin gel culture system that selectively expands adult mouse MuSCs from bulk skeletal muscle preparations without the need for prior cell sorting [2]. Could this represent the innovative breakthrough that muscle regeneration strategies are waiting for?

The inspiration for this study derived from a report describing the successful expansion of freshly sorted MuSCs using a two-dimensional (2D) hydrogel culture system [3]. Moving to the third dimension made sense to the authors, given the 3D microarchitecture niche of MuSCs in the body, and this was achieved using an easily prepared soft fibrin gel [4]. When compared to the widely used Matrigel substrate, the soft fibrin gel selectively favored the survival and proliferation of sorted MuSCs while inhibiting their differentiation (See Figure).

However, the study soon established that the soft fibrin gel also possessed the ability to selectively expand MuSCs from unsorted bulk muscle cells without a need for sorting pure MuSC, a great advantage given the scarcity of stem cells in adult muscle tissue. Encouragingly, fibrin gel-expanded MuSCs could form contractile myotubes in vitro and engraft in vivo following transplantation into pre-injured hind limb muscles of NOD/SCID mice.

But just how does the soft fibrin gel work?! The authors suggest that the elasticity of the gel caused apoptosis in muscle fibroblasts while the presence of αvβ3 integrin enabled the survival and expansion of MuSCs, with the two modes combining to promote the selective ex vivo expansion of MuSCs from bulk skeletal muscle cells.

With the description of a simple and cheap method to selectively expand MuSCs from bulk muscle cells, the authors may have provided a means to greatly advance muscle regeneration strategies for various disorders. In this vein, Zhu et al also note that their system may enable customized genome editing via CRISPR/Cas9 technology to correct mutations in disease-causing genes in MuSCs. 

To see just how successful this selective culture system will be, stay tuned to the Stem Cells Portal.

References

  1. Tarnok A, Ulrich H, and Bocsi J. Phenotypes of stem cells from diverse origin. Cytometry A 2010;77:6-10.
  2. Zhu P, Zhou Y, Wu F, et al. Selective Expansion of Skeletal Muscle Stem Cells from Bulk Muscle Cells in Soft Three-Dimensional Fibrin Gel. STEM CELLS Translational Medicine 2017;6:1412-1423.
  3. Gilbert PM, Havenstrite KL, Magnusson KE, et al. Substrate elasticity regulates skeletal muscle stem cell self-renewal in culture. Science 2010;329:1078-1081.
  4. Janmey PA, Winer JP, and Weisel JW. Fibrin gels and their clinical and bioengineering applications. J R Soc Interface 2009;6:1-10.