Abstract
BackgroundThe development of cellular therapies to treat muscle wastage with disease or age is paramount. Resident muscle satellite cells are not currently regarded as a viable cell source due to their limited migration and growth capability ex vivo. This study investigated the potential of muscle-derived PW1+/Pax7– interstitial progenitor cells (PICs) as a source of tissue-specific stem/progenitor cells with stem cell properties and multipotency.MethodsSca-1+/PW1+ PICs were identified on tissue sections from hind limb muscle of 21-day-old mice, isolated by magnetic-activated cell sorting (MACS) technology and their phenotype and characteristics assessed over time in culture. Green fluorescent protein (GFP)-labelled PICs were used to determine multipotency in vivo in a tumour formation assay.ResultsIsolated PICs expressed markers of pluripotency (Oct3/4, Sox2, and Nanog), were clonogenic, and self-renewing with >60 population doublings, and a population doubling time of 15.8 ± 2.9 h. PICs demonstrated an ability to generate both striated and smooth muscle, whilst also displaying the potential to differentiate into cell types of the three germ layers both in vitro and in vivo. Moreover, PICs did not form tumours in vivo.ConclusionThese findings open new avenues for a variety of solid tissue engineering and regeneration approaches, utilising a single multipotent stem cell type isolated from an easily accessible source such as skeletal muscle.
Highlights
The development of cellular therapies to treat muscle wastage with disease or age is paramount
Abundance of PW1+ PW1-positive interstitial cell (PIC) and satellite cells decreases into old age Expression of PW1+ PICs and satellite cells were assessed by immunohistochemistry on hind limb skeletal muscle cross-sections at 3, 10, and 21 days and 2 years
The number of PW1+ PICs and PW1+ satellite cells decreases with age, yet the proportion of PW1+ quiescent satellite cells to PW1+ PICs increases, which suggests PW1+ PICs are declining at a faster rate with age
Summary
The development of cellular therapies to treat muscle wastage with disease or age is paramount. This study investigated the potential of muscle-derived PW1+/Pax7– interstitial progenitor cells (PICs) as a source of tissue-specific stem/progenitor cells with stem cell properties and multipotency. Muscular dystrophy results in progressive skeletal muscle weakness and wastage [1] due to defects and/or the inability to make the protein dystrophin and other associated protein complexes. DMD is a progressive muscle wasting disease which affects approximately 1 in 3500 boys and often results in death due to respiratory failure before. Muscle degeneration occurs with ageing (termed sarcopenia) where the body’s ability to replace muscle fibres decreases resulting in a progressive loss of muscle mass with a reduction in the cross-sectional area of muscle fibres [3]. 20% of all 60–70 year olds have sarcopenia, and this figure rises to 50% in those over 75 years [4]
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