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Stem cell therapy for macular degeneration

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Induced Pluripotent Stem Cell taken from Blood Cell and converted in RPE Cell

Stem cell therapy for macular degeneration is the use of stem cells to heal, replace dead or damaged cells of the macula in the retina. Stem cell based therapies using bone marrow stem cells as well as retinal pigment epithelial transplantation are being studied.[1] A number of trials have occurred in humans with encouraging results.[2][3]

Historical background

In 1959, the first fetal retinal transplant into the anterior chamber of the eyes of animals was reported. Cell culture experiments on RPE were carried out in 1980. Cultured human RPE cells were transplanted into the eyes of animals, first with open techniques and methods and later with closed cavity vitrectomy techniques.[1]

In 1991, Gholam Peyman transplanted RPE (Retinal Pigment Epithelium) in humans but with limited success rate. Later, allogenic fetal RPE cell transplantation was tried in which immune rejection of the graft was a major problem. It has also been observed that the rejection rates were lower in dry AMD than that in wet AMD. Autologous RPE transplantation is conventionally done employing two techniques, namely, RPE suspension and autologous full-thickness RPE-choroid transplantation. Encouraging clinical outcomes has already been reported with the transplantation of the autologous RPE choroid from the periphery of the eye to a disease affected portion.[4]

Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. "Sheets of retinal cells used by the team are harvested from aborted fetuses, which some people find objectionable." When these sheets are transplanted over the damaged cornea, the stem cells stimulate renewed repair, eventually restore vision.[5] The such development was in June 2005, when researchers at the Queen Victoria Hospital of Sussex, England were able to restore the sight of forty people using the same technique. The group, led by Sheraz Daya, was able to successfully use adult stem cells obtained from the patient, a relative, or even a cadaver.[6]

In September 2014, the team of surgeons from Riken Institute's Center for Developmental Biology in Kobe, (Japan), led by Masayo Takahashi succeeded in a world-first transplanting of cells made from induced pluripotent stem cells into a human body. The operation was conducted as a clinical study and involved creating a retinal sheet from iPS cells, which were developed by Shinya Yamanaka. iPS cells are created by removing mature cells from an individual and reprogramming these cells back to an embryonic state. The retinal sheet was transplanted into a female patient in her 70s with age related macular degeneration (AMD), an eye complication that blurs the central field of vision and can progress into blindness. The iPS cells were hoped to stop the progression of AMD. The team used iPS cells made from the patient's own skin cells. Then in March 2017 team carried out the world's first successful transplant of retinal cells created from donor iPS cells into the eye of a patient with advanced wet age-related macular degeneration.[7] Time and cost used in the surgery has been significantly reduced by using super donor cells, cells derived from people with special white blood cell types that aren't rejected by the immune systems of receiving patients. During the surgery the patient received a transplant of approximately 250,000 retinal pigment epithelial cells into the eye generated from donor-derived iPSCs. Results of this landmark study were published in the New England Journal of Medicine.[8]

See also

Bibliography

  • Atala, A. Human embryonic stem cells: early hints on safety and efficacy. Lancet 379, 689–690 (2012).
  • Bharti, K. et al. Developing cellular therapies for retinal degenerative diseases. Invest. Ophthalmol. Vis. Sci. 55, 1191–1202 (2014).
  • Bhutto, I. & Lutty, G. Understanding age-related macular degeneration (AMD): relationships between the photoreceptor/retinal pigment epithelium/Bruch's membrane/choriocapillaris complex. Mol. Aspects Med. 33, 295–317 (2012).
  • Carr, A.J. et al. Development of human embryonic stem cell therapies for age-related macular degeneration. Trends Neurosci. 36, 385–395 (2013).
  • Chen FK, Uppal GS, MacLaren RE, Coffey PJ, Rubin GS, Tufail A, Aylward GW, Da Cruz L. (2009) Long-term visual and microperimetry outcomes following autologous retinal pigment epithelium choroid graft for neovascular age-related macular degeneration. Clin Exp Ophthalmol. 2009 Apr; 37(3):275-85.
  • Haruta, M. et al. In vitro and in vivo characterization of pigment epithelial cells differentiated from primate embryonic stem cells. Invest. Ophthalmol. Vis. Sci. 45, 1020–1025 (2004).
  • John S, Natarajan S, Parikumar P, Shanmugam PM, Senthilkumar R, Green DW, Abraham SJ (2013). "Choice of Cell Source in Cell-Based Therapies for Retinal Damage due to Age-Related Macular Degeneration: A Review". Journal of Ophthalmology. 2013: 1–9. doi:10.1155/2013/465169. PMC 3654320. PMID 23710332.
  • Mandai, M. et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N. Engl. J. Med. 376, 1038–1046 (2017).
  • Muthiah, M.N. et al. Adaptive optics imaging shows rescue of macula cone photoreceptors. Ophthalmology 121, 430–431.e3 (2014).
  • Nazari, H. et al. Stem cell based therapies for age-related macular degeneration: The promises and the challenges. Prog. Retin. Eye Res. 48, 1–39 (2015).
  • Riken Center for Developmental Biology. "Information on proposed pilot study of the safety and feasibility of transplantation of autologous hiPSC-derived retinal pigment epithelium (RPE) cell sheets in patients with neovascular age-related macular degeneration". Research. Archived from the original on 26 June 2013. Retrieved 23 July 2013.
  • Rosenfeld, P.J. et al. Ranibizumab for neovascular age-related macular degeneration. N. Engl. J. Med. 355, 1419–1431 (2006).
  • Russell, Peter. Macular Degeneration: Stem Cells Restore Sight in Small Study - Medscape - Mar 21, 2018.
  • Schwartz, S.D. 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 385, 509–516 (2015).
  • Vugler, A. et al. Elucidating the phenomenon of HESC-derived RPE: anatomy of cell genesis, expansion and retinal transplantation. Exp. Neurol. 214, 347–361 (2008).

References

  1. ^ a b John S, Natarajan S, Parikumar P, Shanmugam PM, Senthilkumar R, Green DW, Abraham SJ (2013). "Choice of Cell Source in Cell-Based Therapies for Retinal Damage due to Age-Related Macular Degeneration: A Review". Journal of Ophthalmology. 2013: 1–9. doi:10.1155/2013/465169. PMC 3654320. PMID 23710332.
  2. ^ Carr AJ, Smart MJ, Ramsden CM, Powner MB, da Cruz L, Coffey PJ (July 2013). "Development of human embryonic stem cell therapies for age-related macular degeneration". Trends in Neurosciences. 36 (7): 385–95. doi:10.1016/j.tins.2013.03.006. PMID 23601133. S2CID 1007033.
  3. ^ Peter Russell. Macular Degeneration: Stem Cells Restore Sight in Small Study - Medscape - Mar 21, 2018.
  4. ^ Chen FK, Uppal GS, MacLaren RE, Coffey PJ, Rubin GS, Tufail A, Aylward GW, Da Cruz L. (2009) Long-term visual and microperimetry outcomes following autologous retinal pigment epithelium choroid graft for neovascular age-related macular degeneration. Clin Exp Ophthalmol. 2009 Apr; 37(3):275-85.
  5. ^ Fetal tissue restores lost sight MedicalNewsToday. 28 October 2004
  6. ^ "Stem cells used to restore vision". 28 April 2005 – via news.bbc.co.uk.
  7. ^ "First donor iPSC-derived RPE cell transplantation in AMD patient". RIKEN Center for Developmental Biology. 4 April 2017. Retrieved 6 September 2017.
  8. ^ Mandai, Michiko; Watanabe, Akira; Kurimoto, Yasuo; Hirami, Yasuhiko; Morinaga, Chikako; Daimon, Takashi; Fujihara, Masashi; Akimaru, Hiroshi; Sakai, Noriko (2017-03-16). "Autologous Induced Stem-Cell–Derived Retinal Cells for Macular Degeneration". New England Journal of Medicine. 376 (11): 1038–1046. doi:10.1056/nejmoa1608368. ISSN 0028-4793. PMID 28296613. S2CID 27993960.
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