Study of regenerative potential of human perivascular cells expressing DUX4

Introduction. In vitro data demonstrate that estrogens improve differentiation of myoblasts deriving from FSHD patients, counteracting muscle differentiation impairment caused by the homeobox protein DUX4. Objectives. We aim to assess in vivo estrogen activity on regenerative potential of muscle precursor cells (perivascular cells, PVCs) derived from healthy individuals and engineered to express DUX4, or derived from FSHD patients. Methods. Cherry-expressing PVCs were implanted into injured hindlimb-tibial muscle of NSG female mice treated with 17?-estradiol (E2) or fulvestrant. Animals were monitored by fluorescence emission and by functional treadmill test, and molecularly by IHC, gene and protein expression. Results: Human PVCs are able to participate to muscle regeneration of injured muscle. Preliminary data show that DUX4 reduces the performance of implanted PVCs whereas 17?-estradiol is able to recover it. Conclusions: These data indicate the usefulness of PVCs to study in vivo muscle differentiation of FSHD and suggest the potential protective function of estrogen.