Department of Biochemical Science, University of Florence, 50134 Florence, Italy.
Mol Biol Cell. 2010 Mar 15;21(6):848-59. doi: 10.1091/mbc.e09-04-0310. Epub 2010 Jan 20.
Mesoangioblasts are progenitor endowed with multipotent mesoderm differentiation ability. Despite the promising results obtained with mesoangioblast transplantation in muscle dystrophy, an improvement of their efficient engrafting and survival within damaged muscles, as well as their ex vivo activation/expansion and commitment toward myogenic lineage, is highly needed and should greatly increase their therapeutic potential. We show that globular adiponectin, an adipokine endowed with metabolic and differentiating functions for muscles, regulates vital cues of mesoangioblast cell biology. The adipokine drives mesoangioblasts to entry cell cycle and strongly counteracts the apoptotic process triggered by growth factor withdrawal, thereby serving as an activating and prosurvival stem cell factor. In addition, adiponectin provides a specific protection against anoikis, the apoptotic death due to lack of anchorage to extracellular matrix, suggesting a key protective role for these nonresident stem cells after systemic injection. Finally, adiponectin behaves as a chemoattractive factor toward mature myotubes and stimulates their differentiation toward the skeletal muscle lineage, serving as a positive regulator in mesoangioblast homing to injured or diseased muscles. We conclude that adiponectin exerts several advantageous effects on mesoangioblasts, potentially valuable to improve their efficacy in cell based therapies of diseased muscles.
间质成肌细胞是一种具有多能性中胚层分化能力的祖细胞。尽管间质成肌细胞移植在肌肉萎缩症方面取得了有希望的结果，但仍需要提高其在受损肌肉中的有效植入和存活能力，以及体外激活/扩增和向肌源性谱系的分化能力，这将极大地增加其治疗潜力。我们发现，球形脂联素是一种具有代谢和肌肉分化功能的脂肪因子，调节间质成肌细胞生物学的重要信号。该脂肪因子促使间质成肌细胞进入细胞周期，并强烈抑制生长因子撤出引发的细胞凋亡过程，从而作为一种激活和促进生存的干细胞因子。此外，脂联素为间质成肌细胞提供了一种针对锚定缺失导致的凋亡死亡（即失巢凋亡）的特异性保护，提示这些非驻留干细胞在全身注射后具有关键的保护作用。最后，脂联素作为一种趋化因子，作用于成熟的肌管，并刺激它们向骨骼肌谱系分化，作为间质成肌细胞归巢至受损或患病肌肉的正向调节因子。我们得出结论，脂联素对间质成肌细胞具有多种有利影响，可能有助于提高其在治疗患病肌肉的细胞疗法中的疗效。
