Tissue Engineering And Nanotheranostics

“9.61x6.69” b2815 Tissue Engineering and Nanotheranostics

Engineering Approaches for Creating Skeletal Muscle 5

adult. These processes can be broadly divided into two categories:

myogenesis and regeneration. Myogenesis encompasses the

development of muscle tissue in the embryo, and continues in some

capacities until adulthood. Its role is generating new muscle, adding

to the size and strength of an organism. On the other hand, regenera-

tion is responsible for repairing muscle tissue from many types of

injuries. Both of these modes of generating muscle tissue are worth

considering when deciding on viable tissue engineering approaches.

For example, the myogenic processes may be best suited for generat-

ing muscle from early stem cells. Regeneration will likely make a

better model for muscle generated from adult stem cells such as the

monopotent SCs.

2.1. Myogenesis

Myogenesis is a process that begins in the embryonic somite and is

generally thought to occur in four distinct stages: embryonic, fetal,

neonatal, and adult (Fig. 1). The first two stages, embryonic and fetal,

occur prenatal. The third stage, neonatal, displays extensive prolifera-

tion and maturation of muscles. Finally, the fourth stage, adult, pri-

marily exhibits quiescent stem cells termed SCs.18,19 Each of these

stages can be identified by the type of cells present, expression of

specific surface proteins, active signaling pathways, and the cells pro-

liferative capacity. However, there is some overlap seen between the

stages and there have not been clearly established guidelines as to

when each stage begins or ends.

The first stage, embryonic myogenesis, initiates in the somite. At

this stage, myogenic progenitors express Pax3 and Pax7 transcription

factors, which are induced through the Wnt, Shh, and BMP signaling

pathways.^20 Pax3 is expressed first during the somite formation, but is

progressively restricted as myogenic progenitors proliferate.^21 As Pax

expression reduces, myogenic progenitors begin to express more Pax

and start differentiation into myoblasts; initiating the second stage,

fetal myogenesis. Upon differentiation, Pax7 expression is greatly

reduced or absent, and expression of myogenic regulatory factors

(MRFs) begin. The earliest MRFs to be expressed are Myf5 and

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