PLoS One. 2015 Jun 24;10(6):e0128973
Leow SN1, Luu CD2, Hairul Nizam MH1, Mok PL3, Ruhaslizan R1, Wong HS1, Wan Abdul Halim WH1, Ng MH4, Ruszymah BH4, Chowdhury SR4, Bastion ML1, Then KY1
1Department of Ophthalmology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.2Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye & Ear Hospital, Melbourne, Australia. 3Department of Obstetrics & Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia; Genetics & Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia. 4Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
Purpose: To investigate the safety and efficacy of subretinal injection of human Wharton’s Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) rats.
Methods: RCS rats were divided into 2 groups: hWJ-MSCs treated group (n = 8) and placebo control group (n = 8). In the treatment group, hWJ-MSCs from healthy donors were injected into the subretinal space in one eye of each rat at day 21. Control group received saline injection of the same volume. Additional 3 animals were injected with nanogold-labelled stem cells for in vivo tracking of cells localisation using a micro-computed tomography (microCT). Retinal function was assessed by electroretinography (ERG) 3 days before the injection and repeated at days 15, 30 and 70 after the injection. Eyes were collected at day 70 for histology, cellular and molecular studies.
Results: No retinal tumor formation was detected by histology during the study period. MicroCT scans showed that hWJ-MSCs stayed localised in the eye with no systemic migration. Transmission electron microscopy showed that nanogold-labelled cells were located within the subretinal space. Histology showed preservation of the outer nuclear layer (ONL) in the treated group but not in the control group. However, there were no significant differences in the ERG responses between the groups. Confocal microscopy showed evidence of hWJ-MSCs expressing markers for photoreceptor, Müller cells and bipolar cells.
Conclusions: Subretinal injection of hWJ-MSCs delay the loss of the ONL in RCS rats. hWJ-MSCs appears to be safe and has potential to differentiate into retinal-like cells. The potential of this cell-based therapy for the treatment of retinal dystrophies warrants further studies.