Safety and efficacy of human Wharton's Jelly-derived mesenchymal stem cells therapy for retinal degeneration

S. N. Leow, Chi D. Luu, M. H Hairul Nizam, P. L. Mok, R. Ruhaslizan, H. S. Wong, Wan Haslina Wan Abdul Halim, Min Hwei Ng, Ruszymah Idrus, Shiplu Roy Chowdhury, Mae-Lynn Catherine Bastion, K. Y. Then

Research output: Contribution to journalArticle

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Abstract

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 hWJMSCs 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.

Original languageEnglish
Article numbere0128973
JournalPLoS One
Volume10
Issue number6
DOIs
Publication statusPublished - 24 Jun 2015

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Wharton Jelly
Retinal Degeneration
jellies
Cell- and Tissue-Based Therapy
Stem cells
Mesenchymal Stromal Cells
stem cells
Safety
therapeutics
Histology
Injections
Rats
injection
surgeons
Electroretinography
histology
electroretinography
eyes
rats
Control Groups

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Leow, S. N., Luu, C. D., Nizam, M. H. H., Mok, P. L., Ruhaslizan, R., Wong, H. S., ... Then, K. Y. (2015). Safety and efficacy of human Wharton's Jelly-derived mesenchymal stem cells therapy for retinal degeneration. PLoS One, 10(6), [e0128973]. https://doi.org/10.1371/journal.pone.0128973

Safety and efficacy of human Wharton's Jelly-derived mesenchymal stem cells therapy for retinal degeneration. / Leow, S. N.; Luu, Chi D.; Nizam, M. H Hairul; Mok, P. L.; Ruhaslizan, R.; Wong, H. S.; Wan Abdul Halim, Wan Haslina; Ng, Min Hwei; Idrus, Ruszymah; Chowdhury, Shiplu Roy; Bastion, Mae-Lynn Catherine; Then, K. Y.

In: PLoS One, Vol. 10, No. 6, e0128973, 24.06.2015.

Research output: Contribution to journalArticle

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abstract = "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 hWJMSCs expressing markers for photoreceptor, M{\"u}ller 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.",
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AU - Luu, Chi D.

AU - Nizam, M. H Hairul

AU - Mok, P. L.

AU - Ruhaslizan, R.

AU - Wong, H. S.

AU - Wan Abdul Halim, Wan Haslina

AU - Ng, Min Hwei

AU - Idrus, Ruszymah

AU - Chowdhury, Shiplu Roy

AU - Bastion, Mae-Lynn Catherine

AU - Then, K. Y.

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N2 - 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 hWJMSCs 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.

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