Survival and Migration of Pre-induced Adult Human Peripheral Blood Mononuclear Cells in Retinal Degeneration Slow (rds) Mice Three Months After Subretinal Transplantation

Overview

Journal Curr Stem Cell Res Ther

Publisher Bentham Science Publishers

Specialties Cell Biology
Pharmacology

Date 2013 Dec 20

PMID 24350910

Citations 10

Authors

Yuting Peng

Yichi Zhang

Bing Huang

Yan Luo

Min Zhang

Kaijing Li

Weihua Li

Wencong Wen

Shibo Tang

Affiliations

Soon will be listed here.

Abstract

Introduction: Retinitis pigmentosa (RP), an inherited disease characterized by progressive loss of photoreceptors and retinal pigment epithelium, is a leading genetic cause of blindness. Cell transplantation to replace lost photoreceptors is a potential therapeutic strategy, but technical limitations have prevented clinical application. Adult human peripheral blood mononuclear cells (hPBMCs) may be an ideal cell source for such therapies. This study examined the survival and migration of pre-induced hPBMCs three months after subretinal transplantation in the retinal degeneration slow (rds) mouse model of RP.

Materials And Methods: Freshly isolated adult hPBMCs were pre-induced by co-culture with neonatal Sprague-Dawley (SD) rat retinal tissue for 4 days in neural stem cell medium. Pre-induced cells were labeled with CMDiI for tracing and injected into the right subretinal space of rds mice by the trans-scleral approach. After two and three months, right eyes were harvested and transplanted cell survival and migration examined in frozen sections and wholemount retinas. Immunofluorescence in whole-mount retinas was used to detect the expression of human neuronal and photoreceptors protein markers by transplanted cells.

Results: Pre-induced adult hPBMCs could survive in vivo and migrate to various parts of the retina. After two and three months, transplanted cells were observed in the ciliary body, retinal outer nuclear layer, inner nuclear layer, ganglion cell layer, optic papilla, and within the optic nerve. The neuronal and photoreceptor markers CD90/Thy1, MAP-2, nestin, and rhodopsin were expressed by subpopulations of CM-DiI-positive cells three months after subretinal transplantation.

Conclusion: Pre-induced adult hPBMCs survived for at least three months after subretinal transplantation, migrated throughout the retina, and expressed human protein markers. These results suggest that hPBMCs could be used for cell replacement therapy to treat retinal degenerative diseases.

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References

Pittack C, Grunwald G, Reh T . Fibroblast growth factors are necessary for neural retina but not pigmented epithelium differentiation in chick embryos. Development. 1997; 124(4):805-16. DOI: 10.1242/dev.124.4.805. View

Zhang Y, Luo Y, Li K, Zhang M, Huang B, Peng Y . Pre-induced adult human peripheral blood mononuclear cells migrate widely into the degenerative retinas of rd1 mice. Cytotherapy. 2013; 15(11):1416-25. DOI: 10.1016/j.jcyt.2013.05.025. View

Zhang Y, Huang B . Peripheral blood stem cells: phenotypic diversity and potential clinical applications. Stem Cell Rev Rep. 2012; 8(3):917-25. DOI: 10.1007/s12015-012-9361-z. View

Soleymaninejadian E, Pramanik K, Samadian E . Immunomodulatory properties of mesenchymal stem cells: cytokines and factors. Am J Reprod Immunol. 2011; 67(1):1-8. DOI: 10.1111/j.1600-0897.2011.01069.x. View

Chacko D, Rogers J, Turner J, Ahmad I . Survival and differentiation of cultured retinal progenitors transplanted in the subretinal space of the rat. Biochem Biophys Res Commun. 2000; 268(3):842-6. DOI: 10.1006/bbrc.2000.2153. View

Ohta K, Ito A, Tanaka H . Neuronal stem/progenitor cells in the vertebrate eye. Dev Growth Differ. 2008; 50(4):253-9. DOI: 10.1111/j.1440-169X.2008.01006.x. View

Macneil A, Pearson R, MacLaren R, Smith A, Sowden J, Ali R . Comparative analysis of progenitor cells isolated from the iris, pars plana, and ciliary body of the adult porcine eye. Stem Cells. 2007; 25(10):2430-8. DOI: 10.1634/stemcells.2007-0035. View

Lisianyi M . [Mesenchymal stem cells and their immunological properties]. Fiziol Zh (1994). 2013; 59(3):126-34. View

Inoue Y, Iriyama A, Ueno S, Takahashi H, Kondo M, Tamaki Y . Subretinal transplantation of bone marrow mesenchymal stem cells delays retinal degeneration in the RCS rat model of retinal degeneration. Exp Eye Res. 2007; 85(2):234-41. DOI: 10.1016/j.exer.2007.04.007. View

10.

Milwid J, Ichimura T, Li M, Jiao Y, Lee J, Yarmush J . Secreted factors from bone marrow stromal cells upregulate IL-10 and reverse acute kidney injury. Stem Cells Int. 2013; 2012:392050. PMC: 3539665. DOI: 10.1155/2012/392050. View

11.

HAWKINS R, Jansen H, Sanyal S . Development and degeneration of retina in rds mutant mice: photoreceptor abnormalities in the heterozygotes. Exp Eye Res. 1985; 41(6):701-20. DOI: 10.1016/0014-4835(85)90179-4. View

12.

Schormann W, Hammersen F, Brulport M, Hermes M, Bauer A, Rudolph C . Tracking of human cells in mice. Histochem Cell Biol. 2008; 130(2):329-38. DOI: 10.1007/s00418-008-0428-5. View

13.

Meyer J, Katz M, Maruniak J, Kirk M . Embryonic stem cell-derived neural progenitors incorporate into degenerating retina and enhance survival of host photoreceptors. Stem Cells. 2005; 24(2):274-83. PMC: 3381839. DOI: 10.1634/stemcells.2005-0059. View

14.

Ribeiro-Resende V, Pimentel-Coelho P, Mesentier-Louro L, Mendez R, Mello-Silva J, Cabral-da-Silva M . Trophic activity derived from bone marrow mononuclear cells increases peripheral nerve regeneration by acting on both neuronal and glial cell populations. Neuroscience. 2009; 159(2):540-9. DOI: 10.1016/j.neuroscience.2008.12.059. View

15.

Li N, Li X, Yuan J . Effects of bone-marrow mesenchymal stem cells transplanted into vitreous cavity of rat injured by ischemia/reperfusion. Graefes Arch Clin Exp Ophthalmol. 2008; 247(4):503-14. DOI: 10.1007/s00417-008-1009-y. View

16.

Li Y, Atmaca-Sonmez P, Schanie C, Ildstad S, Kaplan H, Enzmann V . Endogenous bone marrow derived cells express retinal pigment epithelium cell markers and migrate to focal areas of RPE damage. Invest Ophthalmol Vis Sci. 2007; 48(9):4321-7. DOI: 10.1167/iovs.06-1015. View

17.

Andrade W, Seabrook T, Johnston M, Hay J . The use of the lipophilic fluorochrome CM-DiI for tracking the migration of lymphocytes. J Immunol Methods. 1996; 194(2):181-9. DOI: 10.1016/0022-1759(96)00083-x. View

18.

Wallace V . Stem cells: a source for neuron repair in retinal disease. Can J Ophthalmol. 2007; 42(3):442-6. DOI: 10.3129/can j ophthalmol.i07-047. View

19.

Kodama H, Inoue T, Watanabe R, Yasutomi D, Kawakami Y, Ogawa S . Neurogenic potential of progenitors derived from human circulating CD14+ monocytes. Immunol Cell Biol. 2006; 84(2):209-17. DOI: 10.1111/j.1440-1711.2006.01424.x. View

20.

Wu M, Chen G, Hu B . Induced pluripotency for translational research. Genomics Proteomics Bioinformatics. 2013; 11(5):288-93. PMC: 4357792. DOI: 10.1016/j.gpb.2013.08.001. View