Effects of mesenchymal stem cells and their exosomes on the healing of large and refractory macular holes

PurposeTo assess the efficacy of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exos) to promote the healing of large and refractory macular holes (MHs).MethodsSeven patients (age 51-75years old) with large and long-standing idiopathic MHs underwent vitrectomy, internal limiting membrane peeling, MSC (two patients) or MSC-Exo (five patients) intravitreal injection, and heavy silicon oil, air, 20% SF6, or 14% C3F8 tamponade. The MSCs were isolated from human umbilical cord tissue, and MSC-Exos were isolated from the supernatants of cultured MSCs using sequential ultracentrifugation.ResultsFive eyes underwent pars plana vitrectomy (PPV) only, while two underwent PPV combined with cataract surgery. Six MHs were closed, while one remained in a flat-open state. The best-corrected visual acuity (BCVA) was improved in five patients with MH closure and remained unchanged in one patient with MH closure who had a 4-year history of MH. A fibrotic membrane was observed on the surface of the retina in one patient who underwent MSC therapy. One patient who received a higher dose of MSC-Exos exhibited an inflammatory reaction.ConclusionsMSC and MSC-Exo therapy may promote functional and anatomic recovery from MH. MSC-Exo therapy may be a useful and safe method for improving the visual outcomes after surgery for refractory MHs.