» Articles » PMID: 33450191

Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression

Abstract

Recent trials of retinal pigment epithelium (RPE) transplantation for the treatment of disorders such as age-related macular degeneration have been promising. However, limitations of existing strategies include the uncertain survival of RPE cells delivered by cell suspension and the inherent risk of uncontrolled cell proliferation in the vitreous cavity. Human RPE stem cell-derived RPE (hRPESC-RPE) transplantation can rescue vision in a rat model of retinal dystrophy and survive in the rabbit retina for at least 1 month. The present study placed hRPESC-RPE monolayers under the macula of a non-human primate model for 3 months. The transplant was able to recover in vivo and maintained healthy photoreceptors. Importantly, there was no evidence that subretinally transplanted monolayers underwent an epithelial-mesenchymal transition. Neither gliosis in adjacent retina nor epiretinal membranes were observed. These findings suggest that hRPESC-RPE monolayers are safe and may be a useful source for RPE cell replacement therapy.

Citing Articles

Atrophic Macular Degeneration and Stem Cell Therapy: A Clinical Review.

Babighian S, Zanella M, Gattazzo I, Galan A, Gagliano C, DEsposito F Adv Exp Med Biol. 2024; 1474():105-118.

PMID: 39259423 DOI: 10.1007/5584_2024_819.


Advances in retina genetics: Progress, potential, and challenges.

Bansal M Indian J Ophthalmol. 2024; 73(Suppl 1):S31-S36.

PMID: 39257094 PMC: 11834934. DOI: 10.4103/IJO.IJO_3334_23.


Tissue Engineering of Outer Blood Retina Barrier for Therapeutic Development.

Hampton C, Bharti K, Song M Curr Opin Biomed Eng. 2024; 31.

PMID: 38962280 PMC: 11218818. DOI: 10.1016/j.cobme.2024.100538.


Age-related reduction in the functional properties of adult stem cells located in the peripheral region of human retinal pigment epithelium.

Arif W, Narendran S, Kannan N, Ramasamy K, Veerappan M, Chidambaranathan G Indian J Ophthalmol. 2024; 72(Suppl 4):S688-S695.

PMID: 38623706 PMC: 11338411. DOI: 10.4103/IJO.IJO_2491_23.


Towards Precision Ophthalmology: The Role of 3D Printing and Bioprinting in Oculoplastic Surgery, Retinal, Corneal, and Glaucoma Treatment.

Wu K, Tabari A, Mazerolle E, Tran S Biomimetics (Basel). 2024; 9(3).

PMID: 38534830 PMC: 10968161. DOI: 10.3390/biomimetics9030145.


References
1.
Al-Nawaiseh S, Thieltges F, Liu Z, Strack C, Brinken R, Braun N . A Step by Step Protocol for Subretinal Surgery in Rabbits. J Vis Exp. 2016; (115). PMC: 5092014. DOI: 10.3791/53927. View

2.
Salero E, Blenkinsop T, Corneo B, Harris A, Rabin D, Stern J . Adult human RPE can be activated into a multipotent stem cell that produces mesenchymal derivatives. Cell Stem Cell. 2012; 10(1):88-95. DOI: 10.1016/j.stem.2011.11.018. View

3.
Stanzel B, Liu Z, Brinken R, Braun N, Holz F, Eter N . Subretinal delivery of ultrathin rigid-elastic cell carriers using a metallic shooter instrument and biodegradable hydrogel encapsulation. Invest Ophthalmol Vis Sci. 2011; 53(1):490-500. DOI: 10.1167/iovs.11-8260. View

4.
da Cruz L, Fynes K, Georgiadis O, Kerby J, Luo Y, Ahmado A . Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. Nat Biotechnol. 2018; 36(4):328-337. DOI: 10.1038/nbt.4114. View

5.
Bonilha V, Rayborn M, Bhattacharya S, Gu X, Crabb J, Crabb J . The retinal pigment epithelium apical microvilli and retinal function. Adv Exp Med Biol. 2007; 572:519-24. PMC: 2748829. DOI: 10.1007/0-387-32442-9_72. View