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      Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells on Laser-Induced Retinal Injury in Mice

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          Abstract

          Stem cell therapy has shown encouraging results for neurodegenerative diseases. The retina provides a convenient locus to investigate stem cell functions and distribution in the nervous system. In the current study, we investigated the therapeutic potential of bone marrow mesenchymal stem cells (MSCs) by systemic transplantation in a laser-induced retinal injury model. MSCs from C57BL/6 mice labeled with green fluorescent protein (GFP) were injected via the tail vein into mice after laser photocoagulation. We found that the average diameters of laser spots and retinal cell apoptosis were decreased in the MSC-treated group. Interestingly, GFP-MSCs did not migrate to the injured retina. Further examination revealed that the mRNA expression levels of glial fibrillary acidic protein and matrix metalloproteinase-2 were lower in the injured eyes after MSC transplantation. Our results suggest that intravenously injected MSCs have the ability to inhibit retinal cell apoptosis, reduce the inflammatory response and limit the spreading of damage in the laser-injured retina of mice. Systemic MSC therapy might play a role in neuroprotection, mainly by regulation of the intraocular microenvironment.

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          Mesenchymal stem cells for the treatment of neurodegenerative disease.

          Nanette C Joyce, Geralyn Annett, Louisa Wirthlin … (2010)
          Mesenchymal stem cells/marrow stromal cells (MSCs) present a promising tool for cell therapy, and are currently being tested in US FDA-approved clinical trials for myocardial infarction, stroke, meniscus injury, limb ischemia, graft-versus-host disease and autoimmune disorders. They have been extensively tested and proven effective in preclinical studies for these and many other disorders. There is currently a great deal of interest in the use of MSCs to treat neurodegenerative diseases, in particular for those that are fatal and difficult to treat, such as Huntington's disease and amyotrophic lateral sclerosis. Proposed regenerative approaches to neurological diseases using MSCs include cell therapies in which cells are delivered via intracerebral or intrathecal injection. Upon transplantation into the brain, MSCs promote endogenous neuronal growth, decrease apoptosis, reduce levels of free radicals, encourage synaptic connection from damaged neurons and regulate inflammation, primarily through paracrine actions. MSCs transplanted into the brain have been demonstrated to promote functional recovery by producing trophic factors that induce survival and regeneration of host neurons. Therapies will capitalize on the innate trophic support from MSCs or on augmented growth factor support, such as delivering brain-derived neurotrophic factor or glial-derived neurotrophic factor into the brain to support injured neurons, using genetically engineered MSCs as the delivery vehicles. Clinical trials for MSC injection into the CNS to treat traumatic brain injury and stroke are currently ongoing. The current data in support of applying MSC-based cellular therapies to the treatment of neurodegenerative disorders are discussed.
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            Neuroprotective effects of intravitreal mesenchymal stem cell transplantation in experimental glaucoma.

            Keith R G Martin, Nephtali Marina, David P J Hunt … (2010)
            Purpose. Retrograde neurotrophic factor transport blockade has been implicated in the pathophysiology of glaucoma. Stem cell transplantation appears to ameliorate some neurodegenerative conditions in the brain and spinal cord, in part by neurotrophic factor secretion. The present study was conducted to determine whether local or systemic bone marrow-derived mesenchymal stem cell (MSC) transplantation can confer neuroprotection in a rat model of laser-induced ocular hypertensive glaucoma. Methods. MSCs were isolated from the bone marrow of adult wild-type and transgenic rats that ubiquitously express green fluorescent protein. MSCs were transplanted intravitreally 1 week before, or intravenously on the day of, ocular hypertension induction by laser photocoagulation of the trabecular meshwork. Ocular MSC localization and integration were determined by immunohistochemistry. Optic nerve damage was quantified by counting axons within optic nerve cross-sections 4 weeks after laser treatment. Results. After intravitreal transplantation, MSCs survived for at least 5 weeks. Cells were found mainly in the vitreous cavity, though a small proportion of discrete cells migrated into the host retina. Intravitreal MSC transplantation resulted in a statistically significant increase in overall RGC axon survival and a significant decrease in the rate of RGC axon loss normalized to cumulative intraocular pressure exposure. After intravenous transplantation, MSCs did not migrate to the injured eye. Intravenous transplantation had no effect on optic nerve damage. Conclusions. Local, but not systemic, transplantation of MSCs was neuroprotective in a rat glaucoma model. Autologous intravitreal transplantation of MSCs should be investigated further as a potential neuroprotective therapy for glaucoma.
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              Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury.

              A M Parr, C. H. Tator, A. Keating (2007)
              Transplantation of bone marrow-derived mesenchymal stromal cells (MSCs) into the injured brain or spinal cord may provide therapeutic benefit. Several models of central nervous system (CNS) injury have been examined, including that of ischemic stroke, traumatic brain injury and traumatic spinal cord injury in rodent, primate and, more recently, human trials. Although it has been suggested that differentiation of MSCs into cells of neural lineage may occur both in vitro and in vivo, this is unlikely to be a major factor in functional recovery after brain or spinal cord injury. Other mechanisms of recovery that may play a role include neuroprotection, creation of a favorable environment for regeneration, expression of growth factors or cytokines, vascular effects or remyelination. These mechanisms are not mutually exclusive, and it is likely that more than one contribute to functional recovery. In light of the uncertainty surrounding the fate and mechanism of action of MSCs transplanted into the CNS, further preclinical studies with appropriate animal models are urgently needed to better inform the design of new clinical trials.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 27 May 2014
                Publication date Collection: June 2014
                Volume: 15
                Issue: 6
                Pages: 9372-9385
                Affiliations
                [1 ]Tianjin Medical University Eye Hospital and Eye Institute, No. 251, Fukang Road, Nankai District, Tianjin 300384, China; E-Mails: frankjyf@ 123456126.com (Y.J.); yanzhang9927@ 123456163.com (Y.Z.); zhanglingjun08@ 123456163.com (L.Z.)
                [2 ]Department of Ophthalmology, Haibin People’s Hospital of Tianjin, No. 400, Chuangye Road, Binhai New District, Tianjin 300280, China; E-Mail: tongxin1506@ 123456sina.com
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Authors to whom correspondence should be addressed; E-Mails: xiaomzh@ 123456126.com (X.Z.); xiaorli@ 123456163.com (X.L.); Tel.: +86-22-5828-0736 (X.Z.); +86-22-5828-0808 (X.L.); Fax: +86-22-2334-6434 (X.Z. & X.L.).
                Article
                Publisher ID: ijms-15-09372
                DOI: 10.3390/ijms15069372
                PMC ID: 4100100
                PubMed ID: 24871366
                SO-VID: c27e7b8b-a607-4f34-a916-f194ed27d114
                Copyright © © 2014 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 01 April 2014
                Date revision received : 29 April 2014
                Date accepted : 12 May 2014
                Categories
                Subject: Article

                ScienceOpen disciplines: Molecular biology
                Keywords: mesenchymal stem cells,retina,apoptosis,glial fibrillary acidic protein (gfap),matrix metalloproteinase-2 (mmp-2)
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: mesenchymal stem cells, retina, apoptosis, glial fibrillary acidic protein (gfap), matrix metalloproteinase-2 (mmp-2)

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