Delivery of Human iPSC-Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells
Por:
A. BRYMOVÁ, F. RODRIGUEZ-JIMENEZ, A. KONRAD, Y. NEMESH, M. THOTTAPPALI, A. ARTERO-CASTRO, R. NYSHCHUK, A. KOLESNIKOVA, B. MÜLLER, H. STUDENOVSKA, J. JUHASOVA, S. JUHAS, I. VALEKOVA, D. LUKOVIC, C. ALEMAN, T. ARDAN, S. DRUTOVIC, J. MOTLIK, Z. ELLEDEROVA, Z. STRANÁK, M. VEITH, L. LYTVYNCHUK, R. SHARMA, K. BHARTI, G. PETROVSKI, P. JENDELOVA, K. STIEGER and S. ERCEG
Publicada:
1 may 2025
Ahead of Print:
1 abr 2025
Resumen:
In late stages of inherited and acquired retinal diseases such as Stargardt disease (STGD) or dry age-related macular degeneration (AMD), loss of retinal pigment epithelia (RPE) cells and subsequently photoreceptors in the macular area result in a dramatic decline of central visual function. Repopulating this area with functional RPE cells may prevent or decline the progression of photoreceptor loss. In the present study, the viability, survival, and integration of human induced pluripotent stem cell (hiPSC)-derived RPE cells (hiPSC-RPE) is assessed generated using clinical-grade protocol and cultured on a clinically relevant scaffold (poly-L-lactide-co-D, L-lactide, PDLLA) after subretinal implantation in immunosuppressed minipigs for up to 6 weeks. It is shown that transplanted hiPSC-RPE cells maintain the RPE cell features such as cell polarity, hexagonal shape, and cell-cell contacts, and interact closely with photoreceptor outer segments without signs of gliosis or neuroinflammation throughout the entire period of examination. In addition, an efficient immunosuppressing strategy with a continuous supply of tacrolimus is applied. Continuous verification and improvement of existing protocols are crucial for its translation to the clinic. The results support the use of hiPSC-RPE on PDLLA scaffold as a cell replacement therapeutic approach for RPE degenerative diseases.
Filiaciones:
:
Ctr Invest Principe Felipe, Stem Cell Therapies Neurodegenerat Dis Lab, Valencia 46012, Spain
A. KONRAD:
Justus Liebig Univ Giessen, Dept Ophthalmol, D-35390 Giessen, Germany
Y. NEMESH:
Czech Acad Sci, Inst Anim Physiol & Genet, Libechov 27721, Czech Republic
Charles Univ Prague, Fac Sci, Dept Cell Biol, Prague 12800, Czech Republic
M. THOTTAPPALI:
Czech Acad Sci, Inst Macromol Chem, Prague 16200, Czech Republic
:
Ctr Invest Principe Felipe, Stem Cell Therapies Neurodegenerat Dis Lab, Valencia 46012, Spain
R. NYSHCHUK:
Czech Acad Sci, Inst Anim Physiol & Genet, Libechov 27721, Czech Republic
Charles Univ Prague, Fac Sci, Dept Cell Biol, Prague 12800, Czech Republic
A. KOLESNIKOVA:
Czech Acad Sci, Inst Anim Physiol & Genet, Libechov 27721, Czech Republic
Charles Univ Prague, Fac Sci, Dept Cell Biol, Prague 12800, Czech Republic
B. MÜLLER:
Justus Liebig Univ Giessen, Dept Ophthalmol, D-35390 Giessen, Germany
H. STUDENOVSKA:
Czech Acad Sci, Inst Macromol Chem, Prague 16200, Czech Republic
J. JUHASOVA:
Czech Acad Sci, Inst Anim Physiol & Genet, Libechov 27721, Czech Republic
S. JUHAS:
Czech Acad Sci, Inst Anim Physiol & Genet, Libechov 27721, Czech Republic
I. VALEKOVA:
Czech Acad Sci, Inst Anim Physiol & Genet, Libechov 27721, Czech Republic
:
CEU Univ, Univ Cardenal Herrera CEU, Sch Vet Med, Dept Anim Prod & Hlth Publ Vet Hlth & Food Sci &, Alfara Del Patriarca 46115, Spain
C. ALEMAN:
Ctr Invest Principe Felipe, Stem Cell Therapies Neurodegenerat Dis Lab, Valencia 46012, Spain
T. ARDAN:
Czech Acad Sci, Inst Anim Physiol & Genet, Libechov 27721, Czech Republic
S. DRUTOVIC:
Czech Acad Sci, Inst Anim Physiol & Genet, Libechov 27721, Czech Republic
J. MOTLIK:
Czech Acad Sci, Inst Anim Physiol & Genet, Libechov 27721, Czech Republic
Z. ELLEDEROVA:
Czech Acad Sci, Inst Anim Physiol & Genet, Libechov 27721, Czech Republic
Z. STRANÁK:
Charles Univ Prague, Vinohrady Teaching Hosp, 3rd Fac Med, Dept Ophthalmol, Prague 10034, Czech Republic
M. VEITH:
Charles Univ Prague, Vinohrady Teaching Hosp, 3rd Fac Med, Dept Ophthalmol, Prague 10034, Czech Republic
L. LYTVYNCHUK:
Justus Liebig Univ Giessen, Dept Ophthalmol, D-35390 Giessen, Germany
R. SHARMA:
NEI, Ocular & Stem Cell Translat Res Sect, NIH, Bethesda, MD USA
K. BHARTI:
NEI, Ocular & Stem Cell Translat Res Sect, NIH, Bethesda, MD USA
G. PETROVSKI:
Oslo Univ Hosp, Ctr Eye Res, Dept Ophthalmol, N-0192 Oslo, Norway
Univ Oslo, N-0192 Oslo, Norway
Univ Szeged, Fac Med, Dept Ophthalmol, H-6720 Szeged, Hungary
P. JENDELOVA:
Czech Acad Sci, Dept Neuroregenerat, Inst Expt Med, Prague 14220, Czech Republic
K. STIEGER:
Justus Liebig Univ Giessen, Dept Ophthalmol, D-35390 Giessen, Germany
:
Ctr Invest Principe Felipe, Stem Cell Therapies Neurodegenerat Dis Lab, Valencia 46012, Spain
Green Submitted, gold
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