Tissue Engineering And Nanotheranostics

“9.61x6.69” b2815 Tissue Engineering and Nanotheranostics

Engineering Approaches for Creating Skeletal Muscle 7

regulation from the G protein-coupled receptor kinase 2^23 or ephrine

receptors and zinc finger protein transcription factors.^24

2.2. Muscle Regeneration

Adult progenitor stem cells, or SCs, are the primary source of muscle

regeneration. These cells reside in the basement membrane of adult

myofibers and remain mitotically quiescent until needed. During the

quiescent period the cell-intrinsic factors expressed by SCs have been

identified to be Pax7, Foxo3, Notch, TTP, miR-31, and p27KIP1.^25

Following stress to muscle tissue, which can be induced by weight

bearing or trauma from an injury, SCs will become activated and

begin differentiation into myoblasts.^26 These myoblasts will undergo

multiple rounds of division prior to terminal differentiation into

mononuclear myocytes that fuse together to form myofibrils. During

activation many cell-intrinsic factors are expressed including Myf5.^25

After injury a large majority of SCs differentiate into myoblasts; there-

fore, the remaining cells must undergo self-renewal to replenish the

progenitor cell population. The cells in this stage display few cell-

intrinsic factors (Pax7, Spry1, and Foxo3).^25

3. Stem Cell Candidates for Muscle Regeneration

Stem cells are defined as being undifferentiated cells that have the

potential to differentiate into functional tissues of the body. Under

the right conditions they are known to be highly proliferative,

although some often remain dormant in the body’s tissues until a

need arises for generation of new tissue. Many types of stem cells have

been identified, each with varying abilities in terms of the mature cell

types they can give rise to, as well as their potential to proliferate.

Embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs),

and mesenchymal stem cells (MSCs) have all been shown to differen-

tiate into myoblast-like cells and may be able to release beneficial

cytokines to enhance wound healing.27–35 These cell types are cur-

rently at the forefront of muscle tissue engineering.

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