Charge, Sophie B. P., and Michael A. Rudnicki. Cellular and Molecular Regulation of Muscle Regeneration. Physiol Rev 84: 209–238, 2004; 10.1152/physrev.00019.2003.—Under normal circumstances, mamma...

Cellular and Molecular Regulation of Muscle Regeneration

Mesenchymal stem cells (MSCs) are multipotent cells which can give rise to mesenchymal and non-mesenchymal tissues in vitro and in vivo. Whereas in vitro properties such as (trans)differentiation capabilities are well known, there is little information regarding natural distribution and biology in the living organism. To investigate the subject further, we generated long-term cultures of cells with mesenchymal stem cell characteristics from different organs and tissues from adult mice. These populations have morphology, immunophenotype and growth properties similar to bone marrow-derived MSCs. The differentiation potential was related to the tissue of origin. The results indicate that (1) cells with mesenchymal stem characteristics can be derived and propagated in vitro from different organs and tissues (brain, spleen, liver, kidney, lung, bone marrow, muscle, thymus, pancreas); (2) MSC long-term cultures can be generated from large blood vessels such as the aorta artery and the vena cava, as well as from small vessels such as those from kidney glomeruli; (3) MSCs are not detected in peripheral blood. Taken together, these results suggest that the distribution of MSCs throughout the post-natal organism is related to their existence in a perivascular niche. These findings have implications for understanding MSC biology, and for clinical and pharmacological purposes.

/pdf/mesenchymal-stem-cells-reside-in-virtually-all-post-natal-4s1txmgth3.pdf

Mesenchymal stem cells reside in virtually all post-natal organs and tissues

https://www.valadkhanlab.org/599_lectures/Khalil/A%20Long%20Noncoding%20RNA%20Controls%20Muscle%20Differentiation%20by%20Functioning%20as%20a%20Competing%20Endogenous%20RNA.pdf

A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA

Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process invol...

Satellite Cells and the Muscle Stem Cell Niche

Efficient tissue regeneration is dependent on the coordinated responses of multiple cell types. Here, we describe a new subpopulation of fibro/adipogenic progenitors (FAPs) resident in muscle tissue but arising from a distinct developmental lineage. Transplantation of purified FAPs results in the generation of ectopic white fat when delivered subcutaneously or intramuscularly in a model of fatty infiltration, but not in healthy muscle, suggesting that the environment controls their engraftment. These cells are quiescent in intact muscle but proliferate efficiently in response to damage. FAPs do not generate myofibres, but enhance the rate of differentiation of primary myogenic progenitors in co-cultivation experiments. In summary, FAPs expand upon damage to provide a transient source of pro-differentiation signals for proliferating myogenic progenitors.

/pdf/muscle-injury-activates-resident-fibro-adipogenic-2eju7mjynb.pdf

Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis

We assessed viable Pax7−/− mice in 129Sv/J background and observed reduced growth and marked muscle wasting together with a complete absence of functional satellite cells. Acute injury resulted in an extreme deficit in muscle regeneration. However, a small number of regenerated myofibers were detected, suggesting the presence of residual myogenic cells in Pax7-deficient muscle. Rare Pax3+/MyoD+ myoblasts were recovered from Pax7−/− muscle homogenates and cultures of myofiber bundles but not from single myofibers free of interstitial tissues. Finally, we identified Pax3+ cells in the muscle interstitial environment and demonstrated that they coexpressed MyoD during regeneration. Sublaminar satellite cells in hind limb muscle did not express detectable levels of Pax3 protein or messenger RNA. Therefore, we conclude that interstitial Pax3+ cells represent a novel myogenic population that is distinct from the sublaminar satellite cell lineage and that Pax7 is essential for the formation of functional myogenic progenitors from sublaminar satellite cells.

/pdf/distinct-roles-for-pax7-and-pax3-in-adult-regenerative-2dxqvk7kwt.pdf

Distinct roles for Pax7 and Pax3 in adult regenerative myogenesis.

UNLABELLED Islet amyloid polypeptide (IAPP) is the constituent of amyloid deposits in pancreatic islets of type 2 diabetes in man, monkeys, and cats. This 37 amino acid peptide aggregates in vitro to form beta-pleated sheet fibrils. Rodent IAPP has a different amino acid sequence and does not form amyloid either in vitro or in vivo. Fibrillogenic properties of human IAPP (hIAPP) were determined in vitro. The effect of pH and time course of fibril formation was studied by light scattering spectroscopy. Aggregation of hIAPP1-37NH2 and hIAPPTyr20-29 (0.25 mg/mL) was maximal at neutral/basic and acidic pH, respectively. The ultrastructure of hIAPP1-37NH2 fibrils (0.2 mg/mL) was examined using negative staining for electron microscopy. Short fibrils composed of 2 or more filaments were observed at pH 3-9 after 30 min incubation. At pH 7-9, IAPP fibrils formed a gel. After 6 months at pH 3, large sheets of parallel fibrils were seen. Specific binding of 125I-hIAPP1-37NH2 to preformed IAPP fibrils detected by quantitative autoradiography and radioassay was maximal at pH 3. Binding was enhanced by insulin (3.7 nmol/L) and unaffected by glucose, calcium, glucagon, and apolipoprotein E. 125I-hIAPP1-37NH2 bound specifically to islet amyloid in pancreatic tissue sections from type 2 diabetic patients. CONCLUSIONS Binding to preformed IAPP fibrils is maximal at acid pH when hIAPP is largely in soluble form. IAPP is secreted together with insulin from the acidic secretory granules (pH 5.5) to the neutral pH of the extracellular space under normal conditions. These changes in pH together with increased accumulation of extracellular hIAPP in diabetes may promote amyloid formation.

Effect of pH and insulin on fibrillogenesis of islet amyloid polypeptide in vitro.

To investigate the cause of skeletal muscle weakening during aging we examined the sequence of cellular changes in murine muscles. Satellite cells isolated from single muscle fibers terminally differentiate progressively less well with increasing age of donor. This change is detected before decline in satellite cell numbers and all histological changes examined here. In MSVski transgenic mice, which show type IIb fiber hypertrophy, initial muscle weakness is followed by muscle degeneration in the first year of life. This degeneration is accompanied by a spectrum of changes typical of normal muscle aging and a more marked decline in satellite cell differentiation efficiency. On a myoD-null genetic background, in which satellite cell differentiation is defective, the MSVski muscle phenotype is aggravated. This suggests that, on a wild-type genetic background, satellite cells are capable of repairing MSVski fibers and preserving muscle integrity in early life. We propose that decline in myogenic cell differentiation efficiency is an early event in aging-related loss of muscle function, both in normal aging and in some late-onset muscle degenerative conditions.

https://www.physiology.org/doi/pdf/10.1152/ajpcell.00206.2002

Aging-related satellite cell differentiation defect occurs prematurely after Ski-induced muscle hypertrophy.

http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/90651/1/j.cell.2009.11.039.pdf

Sophie Chargé

Papers

Cellular and Molecular Regulation of Muscle Regeneration

Distinct roles for Pax7 and Pax3 in adult regenerative myogenesis.

Effect of pH and insulin on fibrillogenesis of islet amyloid polypeptide in vitro.

Aging-related satellite cell differentiation defect occurs prematurely after Ski-induced muscle hypertrophy.

iPS Cells: Mapping the Policy Issues