In Vitro Differentiation of Human Bone Marrow Stem Cells into Retinal Pigment Epithelium
American Journal of Bioscience and Bioengineering
Volume 3, Issue 4-1, July 2015, Pages: 51-55
Received: Jun. 26, 2015;
Accepted: Jun. 27, 2015;
Published: Jul. 6, 2015
Views 2948 Downloads 119
Nehal Draz, Medical Microbiology and Immunology, Ain Shams University, Cairo, Egypt
Makram F. Attalah, Medical Microbiology and Immunology, Ain Shams University, Cairo, Egypt
Hany M. Shaheen, Medical Microbiology and Immunology, Ain Shams University, Cairo, Egypt
Wael Abo Elkeir, Military Medical Academy, Cairo, Egypt
Introduction: Dysfunction, degeneration, and loss of retinal pigment epithelial (RPE) cells are prominent features of subtypes of retinitis pigmentosa (RP) which is a cause of visual disability. In this condition, there is progressive visual loss that often leads to blindness. A variety of therapeutic approaches to delay the degenerative process are under development, the most promising of which is the stem cell regenerative therapy. Stem cells are self-renewing cells capable of transdifferentiation into a number of cell lineages. Mesenchymal stem cells (MSCs) represent a type of stem cell with remarkable proliferative, regenerative and transdifferentiation ability. Aim of the Work: The aim of this work was to evaluate the ability of bone marrow derived MSCs to differentiate into retinal pigmented epithelial cells in vitro as a step towards regeneration of degenerated retinal cells as in cases of retinitis pigmentosa. Patients and Methods: The present study was carried out on 20 bone marrow samples obtained from donors undergoing bone marrow aspirations, at EL-Maadi Military Hospital. 3 ml bone marrow were aspirated, mesenchymal stem cells were separated and induced to RPE lineage through culture in the presence of nicotinamide NIC and factors from the TGF-b superfamily (Activin A). The BMSC- derived pigmented-like cells were evaluated for the morphology, function, and marker expression of authentic RPE using RT-PCR for RPE65 mRNA. Results: Bone marrow derived mesenchymal stem cells in all samples demonstrated the morphologic characteristics as well as molecular markers of RPE cells after 8 weeks of culture with activin A and nicotinamide. Conclusion: In the present study, compelling evidences support the possibility of differentiation of bone marrow stem cells into retinal pigmented epithelial cells (RPE) which have the morphology, function, and marker expression of authentic RPE.
Makram F. Attalah,
Hany M. Shaheen,
Wael Abo Elkeir,
In Vitro Differentiation of Human Bone Marrow Stem Cells into Retinal Pigment Epithelium, American Journal of Bioscience and Bioengineering. Special Issue: Stem Cells for Neuro-Regeneration: Where Do We Stand.
Vol. 3, No. 4-1,
2015, pp. 51-55.
Bongso A., and Eng Hin Lee (2005): stem cells from bench beside. ISBN: 978-981-4481-16-8 (ebook).Development 127, 4599–4609.
Cai X, Conley S, Naash M (2009): RPE65: Role in the visual cycle, human retinal disease, and gene therapy. Ophthalmic Genet. 2009 Jun; 30(2): 57.
Chong Z.Z, Lin S.H, Li F and Maiese K (2005): The sirtuin inhibitor nicotinamide enhances neuronal cell survival during acute anoxic injury through AKT, BAD, PARP, and mitochondrial associated ‘‘anti-apoptotic’’ path ways. Curr. Neurovasc. Res. 2, 271–285.
da Cruz, L., Chen, F.K., Ahmado, A., Greenwood, J., and Coffey, P. (2007). RPE transplantation and its role in retinal disease. Prog. Retin. Eye Res. 26, 598–635.
Dominici M1, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E.(2006): Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-7.
Doyle A & J.Bryan Griffiths (1998): Cell and Tissue Culture: Laboratory Procedures in Biotechnology. ISBN: 978-0-471-98255-5.
Fahim A, Daiger S, Weleber R (2000): Retinitis Pigmentosa Overview. GeneReviews Advanced Search
Fuhrmann S, Levine E.M and Reh T.A (2000): Extraocular mesenchyme patterns the optic vesicle during early eye development in the embryonic chick. Development 127, 4599–4609.
Fuhrmann, S., Levine, E.M., and Reh, T.A. (2000). Extraocular mesenchyme
Ma J, Zhang D, Laser M, Brownlee N, Re G, Hazen-Martin D, Redmond T, Crouch R (1999): Identification of RPE65 in transformed kidney cells. FEBS Letters 452(3):199-204.
Maria Idelson, Ruslana Alper, Alexey Obolensky, Etti Ben-Shushan, Itzhak Hemo, Nurit Yachimovich-Cohen, et al (2009): Directed Differentiation of Human Embryonic Stem Cells into Functional Retinal Pigment Epithelium Cells. Cell Stem Cell 5, 396–408.
Paquet-Durand F, Silva J, Talukdar T, Johnson L.E, Azadi S, van Veen T, Uefﬁng M, Hauck S.M and Ekstrom P.A (2007): Excessive activation of poly (ADP-ribose) polymerase contributes to inherited photoreceptor degeneration in the retinal degeneration 1 mouse. J. Neurosci. 27, 10311–10319. patterns the optic vesicle during early eye development in the embryonic retinal pigment epithelium cell transplantation. Neuroscience 114, 389–401.
Sauvé (2002): Neuroscience, 114(2):389-401.
Sauve, Y., Girman, S.V., Wang, S., Keegan, D.J., and Lund, R.D. (2002). Preservation of visual responsiveness in the superior colliculus of RCS rats after
Shen C.C, Huang H.M, Ou H.C, Chen H.L, Chen W.C and Jeng K.C (2004): Protective effect of nicotinamide on neuronal cells under oxygen and glucose deprivation and hypoxia/reoxygenation. J. Biomed. Sci. 11, 472–481.
Strauss O (2005): The retinal pigment epithelium in visual function. Physiol.Rev. 85, 845–881.
Zhang Z, Zhang Y, Xiao H, Liang X, Sun D, Peng S.(2012): A gene expression profile of the developing human retinal pigment epithelium Mol Vis. 2012;18:2961-75.