Embryonic stem cells (ESC) |
Derived from the internal cell mass of embryos |
Pluripotent Differentiation into all types of adult cells |
Ethical and immune questions Formation of tumors |
Subretinal applications of RPE derived from embryonic cells: Astellas Institute for Regenerative Medicine, USA, Schwartz et al(2121 Schwartz SD, Hubschman JP, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, et al. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet. 2012;379(9817):713-20.,2222 Schwartz SD, Regillo CD, Lam BL, Eliott D, Rosenfeld PJ, Gregori NZ, et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet. 2015;385(9967):509-16.), (NCT02941991/NCT02445612)(21525 Astellas Institute for Regenerative Medicine Group. A Follow up study to determine the safety and tolerability of sub-retinal transplantation of human embryonic stem cell derived retinal pigmented epithelial (hESC-RPE) cells in patients with stargardt's macular dystrophy (SMD). [cited 2018 Oct 24]. Available from: https://clinicaltrials.gov/ct2/results?cond=&term=NCT02941991+&cntry=&state=&city=&dist=
https://clinicaltrials.gov/ct2/results?c...
,2626 Regenerative Patch Technologies Group. Long term follow-up of sub-retinal transplantation of hesc derived rpe cells in Stargardt macular dystrophy patients. [cited 2018 Oct 24]. Available from: https://clinicaltrials.gov/ct2/results?cond=&term=NCT02445612&cntry=&state=&city=&dist=
https://clinicaltrials.gov/ct2/results?c...
) Regenerative Patch Technologies, USA, clinical trial (NCT02590692)(2727 Regenerative Patch Technologies Group. Study of subretinal implantation of human embryonic stem cell-derived RPE cells in advanced dry AMD. [cited 2018 Oct 24]. Available from: https://clinicaltrials.gov/ct2/show/NCT02590692?cond=dry+amd&draw=2&rank=11
https://clinicaltrials.gov/ct2/show/NCT0...
). Southwest Hospital, China, NCT02749734)(2828 Yin ZQ. Clinical study of subretinal transplantation of human embryo stem cell derived retinal pigment epitheliums in treatment of macular degeneration diseases. [cited 2018 Oct 24]. Available from: https://clinicaltrials.gov/ct2/results?cond=&term=NCT02749734&cntry=&state=&city=&dist=
https://clinicaltrials.gov/ct2/results?c...
) The First Affiliated Hospital of Zhengzhou University, China, (NCT03046407)(2929 Zhou Q. Treatment of dry age related macular degeneration disease with retinal pigment epithelium derived from human embryonic stem cells. [cited 2018 Oct 24]. Available from: https://clinicaltrials.gov/ct2/show/NCT03046407?cond=dry+amd&draw=4&rank=37
https://clinicaltrials.gov/ct2/show/NCT0...
). Universidade Federal de São Paulo (Unifesp), Brazil, (NCT02903576)(3030 Belfort R Jr. Stem cell therapy for outer retinal degenerations. [cited 2018 Oct 24]. Available from: https://clinicaltrials.gov/ct2/results?cond=&term=NCT02903576&cntry=&state=&city=&dist=
https://clinicaltrials.gov/ct2/results?c...
). |
Induced pluripotent stem cells (iPSCs) |
Somatic cells that are terminally differentiated into skin tissues (fibroblasts), genetically reprogrammed by retroviral transduction. |
Pluripotent Absence of ethical problems Low need to use immunosuppressive drugs |
Higher cost Mutations in the cellular reprogramming process |
Subretinal application of RPE derived from iPSCs: Takahashi, RIKEN Institute, Japan. (3131 Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663-76.,3838 Garber K. RIKEN suspends first clinical trial involving induced pluripotent stem cells. Nat Biotechnol. 2015;33(9):890-1.,3939 Pera MF. Stem cells: the dark side of induced pluripotency. Nature. 2011;471(7336):46-7.)
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Bone marrow-derived hematopoietic stem cells (BMDSC) |
Hematopoietic stem cells (HSCs) from the bone marrow of adults (femur, ribs, and sternum), umbilical cords, and the placenta. |
Multipotent No need for systemic immunosuppression |
These cells lack the same potential for transformation in other cells than ESCs |
Intravitreous Injection: Department of Ophthalmology and Vision Science, University of California-Davis Eye Center, EUA, Park et al.(45), (NCT01736059) Faculdade de Medicina de Ribeirão Preto, ( USP), Brazil, Siqueira et al.(77 Siqueira RC, Voltarelli JC, Messias AM, Jorge R. Possible mechanisms of retinal function recovery with the use of cell therapy with bone marrow-derived stem cells. Arq Bras Oftalmol. 2010;73(5):474-9.,88 Siqueira RC. Stem cell therapy for retinal diseases: update. Stem Cell Res Ther. 2011;2(6):50.,4646 Liu Y, Chen SJ, Li SY, Qu LH, Meng XH, Wang Y, et al. Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients. Stem Cell Res Ther. 2017;8(1):209.,4747 Semo M, Haamedi N, Stevanato L, Carter D, Brooke G, Young M, et al. Efficacy and safety of human retinal progenitor cells. Transl Vis Sci Technol. 2016;5(4):6.) (NCT01068561/NCT01518127/ NCT01518842 |
Retinal progenitor cells (RPC) |
Population of immature cells responsible for the production of retinal cells during embryonic development; acquired from ocular tissues of aborted 12-to-16-week fetuses |
Multipotent |
These cells lack the same potential for transformation in other cells than ESCs |
Subretinal application: Liu et al.(4646 Liu Y, Chen SJ, Li SY, Qu LH, Meng XH, Wang Y, et al. Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients. Stem Cell Res Ther. 2017;8(1):209.) Intravitreous injection: jCyte e o California Institute for Regenerative Medicine (CIRM)(49), Barruch Kuppermann(4848 Kuppermann B. Safety and efficacy of intravitreal injection of human retinal progenitor cells in adults with retinitis pigmentosa. [cited 2018 Oct 24]. Available from: https://clinicaltrials.gov/ct2/show/NCT03073733?term=jCyte&rank=1
https://clinicaltrials.gov/ct2/show/NCT0...
), (CT03073733) |