Research ArticleCORNEAL INJURY

Muse cell spheroids have therapeutic effect on corneal scarring wound in mice and tree shrews

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Science Translational Medicine  23 Sep 2020:
Vol. 12, Issue 562, eaaw1120
DOI: 10.1126/scitranslmed.aaw1120

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aMUSEment in sight

Scars from corneal injuries are a major cause of blindness. Stem cell therapy holds promises for treating corneal scarring; however, selecting the source of stem cells is critical for the positive outcome of the cell transplant. Here, Guo et al. evaluated the therapeutic potential of corneal stromal cells (CSCs) derived from multilineage-differentiating stress-enduring (Muse) cells isolated from lipoaspirate. Muse cells showed high stemness, activity, and proliferation. Transplant of Muse-derived CSCs promoted tissue regeneration and reduced scarring in models of corneal injury in mice and tree shrews. The results suggest that Muse-CSCs have therapeutic potential for treating corneal diseases.

Abstract

Stem cell therapy holds promises for treating corneal scarring. Here, we use multilineage-differentiating stress-enduring (Muse) cells to study their differentiation and therapeutic potential for treating corneal injury. Muse cells were isolated from lipoaspirate, which presented biphenotype properties of both pluripotent stem cells and some mesenchymal stem cells. Muse cells expanded by about 100-fold from the initial seeding cell number to Muse spheroids with the maintenance of the Muse cell phenotype and high cell viability at 33 days by static spheroid culture. We revealed that Muse spheroids were activated by the dynamic rotary cell culture system (RCCS), as characterized by increased stemness, improved activity, and enhanced adherence. Gene and protein expression of the pluripotent markers OCT3/4, SOX2, and NANOG and of the proliferation marker KI67 in Muse spheroids cultured under RCCS were higher than those in the static group. These activated Muse spheroids enabled ready differentiation into corneal stromal cells (CSCs) expressing characteristic marker genes and proteins. Furthermore, implantation of Muse cells–differentiated CSCs (Muse-CSCs) laden assembled with two orthogonally stacked stretched compressed collagen (cell-SCC) in mouse and tree shrew wounded corneas prevented the formation of corneal scarring, increased corneal re-epithelialization and nerve regrowth, and reduced the severity of corneal inflammation and neovascularization. cell-SCC retained the capacity to suppress corneal scarring after long-distance cryopreserved transport. Thus, Muse cell therapy is a promising avenue for developing therapeutics for treating corneal scarring.

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