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      Prospect of cell therapy for Parkinson's disease

      review-article
      Anatomy & Cell Biology
      Korean Association of Anatomists
      Parkinson disease, Stem cells, Substantia nigra, Striatum, Putamen

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          Abstract

          The hallmark of Parkinson's disease is on-going degeneration of dopaminergic neurons in the substantia nigra, which may be due to various etiologies. Various approaches to alleviate symptoms are available, such as life-long pharmacological intervention, deep brain stimulation, and transplantation of dopaminergic neuron-containing fetal tissue. However, each of these approaches has a disadvantage. Several studies have shown that various kinds of stem cells, induced pluripotent stem cells, and other cells can differentiate into dopaminergic neurons and may be promising for treating Parkinson's disease in the future. Therefore, this review addresses those cells in terms of their prospects in cell therapy for Parkinson's disease. In addition, the need for safety and efficacy studies, various cell delivery modes and sites, and possible side effects will be discussed.

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          Most cited references47

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          Transplantation of embryonic dopamine neurons for severe Parkinson's disease.

          Transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson's disease has proved beneficial in open clinical trials. However, whether this intervention would be more effective than sham surgery in a controlled trial is not known. We randomly assigned 40 patients who were 34 to 75 years of age and had severe Parkinson's disease (mean duration, 14 years) to receive a transplant of nerve cells or sham surgery; all were to be followed in a double-blind manner for one year. In the transplant recipients, cultured mesencephalic tissue from four embryos was implanted into the putamen bilaterally. In the patients who received sham surgery, holes were drilled in the skull but the dura was not penetrated. The primary outcome was a subjective global rating of the change in the severity of disease, scored on a scale of -3.0 to 3.0 at one year, with negative scores indicating a worsening of symptoms and positive scores an improvement. The mean (+/-SD) scores on the global rating scale for improvement or deterioration at one year were 0.0+/-2.1 in the transplantation group and -0.4+/-1.7 in the sham-surgery group. Among younger patients (60 years old or younger), standardized tests of Parkinson's disease revealed significant improvement in the transplantation group as compared with the sham-surgery group when patients were tested in the morning before receiving medication (P=0.01 for scores on the Unified Parkinson's Disease Rating Scale; P=0.006 for the Schwab and England score). There was no significant improvement in older patients in the transplantation group. Fiber outgrowth from the transplanted neurons was detected in 17 of the 20 patients in the transplantation group, as indicated by an increase in 18F-fluorodopa uptake on positron-emission tomography or postmortem examination. After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa. Human embryonic dopamine-neuron transplants survive in patients with severe Parkinson's disease and result in some clinical benefit in younger but not in older patients.
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            Why are MSCs therapeutic? New data: new insight.

            A Caplan (2009)
            Adult marrow-derived mesenchymal stem cells (MSCs) are able to differentiate into bone, cartilage, muscle, marrow stroma, tendon-ligament, fat and other connective tissues. The questions can be asked, what do MSCs do naturally and where is the MSC niche? New insight and clinical experience suggest that MSCs are naturally found as perivascular cells, summarily referred to as pericytes, which are released at sites of injury, where they secrete large quantities of bioactive factors that are both immunomodulatory and trophic. The trophic activity inhibits ischaemia-caused apoptosis and scarring while stimulating angiogenesis and the mitosis of tissue intrinsic progenitor cells. The immunomodulation inhibits lymphocyte surveillance of the injured tissue, thus preventing autoimmunity, and allows allogeneic MSCs to be used in a variety of clinical situations. Thus, a new, enlightened era of experimentation and clinical trials has been initiated with xenogenic and allogeneic MSCs.
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              Immunomodulation by mesenchymal stem cells and clinical experience.

              Mesenchymal stem cells (MSCs) from adult marrow can differentiate in vitro and in vivo into various cell types, such as bone, fat and cartilage. MSCs preferentially home to damaged tissue and may have therapeutic potential. In vitro data suggest that MSCs have low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes. Instead, MSCs appear to be immunosuppressive in vitro. They inhibit T-cell proliferation to alloantigens and mitogens and prevent the development of cytotoxic T-cells. In vivo, MSCs prolong skin allograft survival and have several immunomodulatory effects, which are presented and discussed in the present study. Possible clinical applications include therapy-resistant severe acute graft-versus-host disease, tissue repair, treatment of rejection of organ allografts and autoimmune disorders.
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                Author and article information

                Journal
                Anat Cell Biol
                ACB
                Anatomy & Cell Biology
                Korean Association of Anatomists
                2093-3665
                2093-3673
                December 2011
                30 December 2011
                : 44
                : 4
                : 256-264
                Affiliations
                Department of Histology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
                Author notes
                Corresponding author: Jeanne Adiwinata Pawitan. Department of Histology, Faculty of Medicine, University of Indonesia, Jl. Salemba 6, Jakarta 10430, Indonesia. Tel: +62-21-3146129, Fax: +62-21-3160108, jeanneadiwip@ 123456fk.ui.ac.id
                Article
                10.5115/acb.2011.44.4.256
                3254879
                22254154
                4f30ad2e-6568-415c-b35e-836b1188c4b7
                Copyright © 2011. Anatomy & Cell Biology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 August 2011
                : 05 September 2011
                : 27 September 2011
                Categories
                Review Article

                Cell biology
                stem cells,striatum,substantia nigra,putamen,parkinson disease
                Cell biology
                stem cells, striatum, substantia nigra, putamen, parkinson disease

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