Abstract
Background aims
Recent advances in stem cell research have raised the possibility of stem cells repairing
or replacing retinal photoreceptor cells that are either dysfunctional or lost in
many retinal diseases. Various types of stem cells have been used to replace retinal
photoreceptor cells. Recently, peripheral blood stem cells, a small proportion of
pluripotent stem cells, have been reported to mainly exist in the peripheral blood
mononuclear cells (PBMCs).
Methods
In this study, the effects of pre-induced adult human PBMCs (hPBMCs) on the degenerative
retinas of rd1 mice were investigated. Freshly isolated adult hPBMCs were pre-induced with the use
of the conditioned medium of rat retinas for 4 days and were then labeled with chloromethyl-benzamidodialkylcarbocyanine
(CM-DiI) and then transplanted into the subretinal space of the right eye of rd1 mice through a trans-scleral approach. The right eyes were collected 30 days after
transplantation. The survival and migration of the transplanted cells in host retinas
were investigated by whole-mount retinas, retinal frozen sections and immunofluorescent
staining.
Results
After subretinal transplantation, pre-induced hPBMCs were able to survive and widely
migrate into the retinas of rd1 mice. A few CM-DiI–labeled cells migrated into the inner nuclear layer and the retinal ganglion
cell layer. Some transplanted cells in the subretinal space of rd1 host mice expressed the human photoreceptor–specific marker rhodopsin.
Conclusions
This study suggests that pre-induced hPBMCs may be a potential cell source of cell
replacement therapy for retinal degenerative diseases.
Key Words
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References
- Embryonic stem cell trials for macular degeneration: a preliminary report.Lancet. 2012; 379: 713-720
- Human photoreceptor transplantation in retinitis pigmentosa: a safety study.Arch Ophthalmol. 1997; 115: 1168-1172
- Human umbilical cord blood-derived mesenchymal stem cells do not differentiate into neural cell types or integrate into the retina after intravitreal grafting in neonatal rats.Stem Cells Dev. 2009; 18: 399-409
Inoue Y, Iriyama A, Ueno S, Takahashi H, Kondo M, Tamaki Y, et al. Subretinal transplantation of bone marrow mesenchymal stem cells delays retinal degeneration in the RCS rat model of retinal degeneration. Exp Eye Res. [Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't]. 2007 2007-08-01;85(2):234–241.
- The transplantation of human fetal neuroretinal cells in advanced retinitis pigmentosa patients: results of a long-term safety study.Exp Neurol. 1999; 157: 58-68
- Transplantation of human central nervous system stem cells-neuroprotection in retinal degeneration.Eur J Neurosci. 2012; 35: 468-477
- E13.5 retinal progenitors induce mouse bone marrow mesenchymal stromal cells to differentiate into retinal progenitor-like cells.Cytotherapy. 2011; 13: 294-303
- Mesenchymal stem cells and potential applications in treating ocular disease.Curr Eye Res. 2010; 35: 941-952
- Effects of bone marrow stromal cell injection in an experimental glaucoma model.Biochem Biophys Res Commun. 2006; 344: 1071-1079
- Muller glia express rhodopsin in a mouse model of inherited retinal degeneration.Neuroscience. 2012; 225: 152-161
- Long-term safety and efficacy of human induced pluripotent stem cell (iPS) grafts in a preclinical model of retinitis pigmentosa.Mol Med. 2012; 18: 1312-1319
- Induced pluripotent stem cell technology for generating photoreceptors.Regen Med. 2011; 6: 469-479
- Peripheral blood stem cells: phenotypic diversity and potential clinical applications.Stem Cell Rev. 2012; 8: 917-925
- Multipotent adult progenitor cell lines originating from the peripheral blood of green fluorescent protein transgenic swine.Stem Cells Dev. 2006; 15: 507-522
- Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing.Am J Pathol. 2006; 169: 1440-1457
- A human peripheral blood monocyte-derived subset acts as pluripotent stem cells.Proc Natl Acad Sci U S A. 2003; 100: 2426-2431
- Human circulating CD14+ monocytes as a source of progenitors that exhibit mesenchymal cell differentiation.J Leukoc Biol. 2003; 74: 833-845
- Circulating very small embryonic-like stem cells in cardiovascular disease.J Cardiovasc Transl Res. 2011; 4: 138-144
- Very small embryonic-like stem cells (VSELs): a new promising candidate for use in cardiac regeneration.Ageing Res Rev. 2011; 10: 173-177
- Transdifferentiation of blood-derived human adult endothelial progenitor cells into functionally active cardiomyocytes.Circulation. 2003; 107: 1024-1032
- Mesenchymal stem cells protect CNS neurons against glutamate excitotoxicity by inhibiting glutamate receptor expression and function.Exp Neurol. 2012; 236: 161-170
- Hematopoietic stem cell graft manipulation as a mechanism of immunotherapy.Int Immunopharmacol. 2003; 3: 1121-1143
- Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure?.Int J Hematol. 2002; 76: 226-247
- Isolation of an adult blood-derived progenitor cell population capable of differentiation into angiogenic, myocardial and neural lineages.Br J Haematol. 2006; 135: 703-714
- Successful engraftment of blood derived normal hemopoietic stem cells in chronic myelogenous leukemia.Exp Hematol. 1981; 9: 684-690
- Adult peripheral blood mononuclear cells transdifferentiate in vitro and integrate into the retina in vivo.Cell Biol Int. 2011; 35: 631-638
- Chondrogenic differentiation of human embryonic stem cells: the effect of the micro-environment.Tissue Eng. 2006; 12: 1687-1697
- Epimorphin is involved in differentiation of rat hepatic stem-like cells through cell-cell contact.Biochem Biophys Res Commun. 2003; 311: 415-423
- Osteogenic differentiation is selectively promoted by morphogenetic signals from chondrocytes and synergized by a nutrient rich growth environment.Connect Tissue Res. 2003; 44: 85-91
- Stem cell niche: structure and function.Annu Rev Cell Dev Biol. 2005; 21: 605-631
- Human adult bone marrow-derived somatic cells rescue vision in a rodent model of retinal degeneration.Exp Eye Res. 2010; 91: 449-455
- Long-term survival and differentiation of retinal neurons derived from human embryonic stem cell lines in un-immunosuppressed mouse retina.Mol Vis. 2012; 18: 920-936
- Cell fate determination in the vertebrate retina.Trends Neurosci. 2012; 35: 565-573
- Secreted inducers in vertebrate eye development: more functions for old morphogens.Curr Opin Neurobiol. 2006; 16: 13-19
- Transplantation of bone marrow-derived mesenchymal stem cells into the developing mouse eye.Acta Histochem Cytochem. 2011; 44: 213-221
- Derivation of multipotent progenitors from human circulating CD14+ monocytes.Exp Hematol. 2010; 38: 557-563
- Retinal remodeling during retinal degeneration.Exp Eye Res. 2005; 81: 123-137
- Retinal remodeling in inherited photoreceptor degenerations.Mol Neurobiol. 2003; 28: 139-147
- Retinal remodeling triggered by photoreceptor degenerations.J Comp Neurol. 2003; 464: 1-16
- XIAP therapy increases survival of transplanted rod precursors in a degenerating host retina.Invest Ophthalmol Vis Sci. 2011; 52: 1567-1572
- Neuroretinal xenotransplantation to immunocompetent hosts in a discordant species combination.Neuroscience. 2008; 152: 526-533
- Grafting of ARPE-19 and Schwann cells to the subretinal space in RCS rats.Invest Ophthalmol Vis Sci. 2005; 46: 2552-2560
- Engraftment of adult neural progenitor cells transplanted to rat retina injured by transient ischemia.Invest Ophthalmol Vis Sci. 2003; 44: 3194-3201
- Retinal repair by transplantation of photoreceptor precursors.Nature. 2006; 444: 203-207
- Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin.Nat Neurosci. 2003; 6: 863-868
- Identification of barriers to retinal engraftment of transplanted stem cells.Invest Ophthalmol Vis Sci. 2010; 51: 960-970
- A comparison of neural differentiation and retinal transplantation with bone marrow-derived cells and retinal progenitor cells.Stem Cells. 2006; 24: 2270-2278
- Current electrophysiology in ophthalmology: a review.Curr Opin Ophthalmol. 2012; 23: 497-505
- Full-field ERG, multifocal ERG and multifocal VEP in patients with retinitis pigmentosa and residual central visual fields.Acta Ophthalmol Scand. 2004; 82: 701-706
Article info
Publication history
Accepted:
May 22,
2013
Received:
December 4,
2012
Identification
Copyright
© 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.