title: Safety and Efficacy of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Therapy for Retinal Degeneration.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: S N
authors.initials: SN
authors.lastname: Leow
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye & Ear Hospital, Melbourne, Australia.
authors.forename: Chi D
authors.initials: CD
authors.lastname: Luu
authors.affiliation: Department of Ophthalmology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: M H
authors.initials: MH
authors.lastname: Hairul Nizam
authors.affiliation: Department 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.
authors.forename: P L
authors.initials: PL
authors.lastname: Mok
authors.affiliation: Department of Ophthalmology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: R
authors.initials: R
authors.lastname: Ruhaslizan
authors.affiliation: Department of Ophthalmology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: H S
authors.initials: HS
authors.lastname: Wong
authors.affiliation: Department of Ophthalmology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Wan Haslina
authors.initials: WH
authors.lastname: Wan Abdul Halim
authors.affiliation: Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: M H
authors.initials: MH
authors.lastname: Ng
authors.affiliation: Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: B H I
authors.initials: BH
authors.lastname: Ruszymah
authors.affiliation: Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: S R
authors.initials: SR
authors.lastname: Chowdhury
authors.affiliation: Department of Ophthalmology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: M L C
authors.initials: ML
authors.lastname: Bastion
authors.affiliation: Department of Ophthalmology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: K Y
authors.initials: KY
authors.lastname: Then
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004596:Electroretinography; D015870:Gene Expression; D006046:Gold / Q000737:chemistry; D006801:Humans; D056965:Injections, Intraocular; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D053768:Metal Nanoparticles / Q000737:chemistry; D051381:Rats; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D013194:Staining and Labeling / Q000379:methods; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous; D059631:Wharton Jelly / Q000166:cytology / Q000502:physiology; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D006046:Gold