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      Stem cell-based approach for the treatment of Parkinson's disease

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          Abstract

          Parkinson’s disease (PD) is the second most common neurodegenerative brain disorder which is around 1.5 times more common in men than in women. Currently, drug medications, surgery, and lifestyle changes are common approaches to PD, while all of them focused on reducing the symptoms. Therefore, regenerative medicine based on stem cell (SC) therapies has raised a promising hope. Various types of SCs have been used in basic and experimental studies relevant to PD, including embryonic pluripotential stem cells, mesenchymal (MSCs) and induced pluripotent SCs (iPSCs). MSCs have several advantages over other counterparts. They are easily accessible which can be obtained from various tissues such as bone marrow, adipose tissue, peripheral blood, etc. with avoiding ethical problems. Therefore, MSCs is attractive clinically because there are no related ethical and immunological concerns . Further studies are needed to answer some crucial questions about the different issues in SC therapy. Accordingly, SC-based therapy for PD also needed more complementary evaluation in both basic and clinical study areas.

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          Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.

          A J Hughes, S Daniel, L Kilford … (1992)
          Few detailed clinico-pathological correlations of Parkinson's disease have been published. The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported. Seventy six had nigral Lewy bodies, and in all of these Lewy bodies were also found in the cerebral cortex. In 24 cases without Lewy bodies, diagnoses included progressive supranuclear palsy, multiple system atrophy, Alzheimer's disease, Alzheimer-type pathology, and basal ganglia vascular disease. The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82%. These observations call into question current concepts of Parkinson's disease as a single distinct morbid entity.
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            Adult rat and human bone marrow stromal cells differentiate into neurons.

            Dale Woodbury, Emily J. Schwarz, Darwin J Prockop … (2000)
            Bone marrow stromal cells exhibit multiple traits of a stem cell population. They can be greatly expanded in vitro and induced to differentiate into multiple mesenchymal cell types. However, differentiation to non-mesenchymal fates has not been demonstrated. Here, adult rat stromal cells were expanded as undifferentiated cells in culture for more than 20 passages, indicating their proliferative capacity. A simple treatment protocol induced the stromal cells to exhibit a neuronal phenotype, expressing neuron-specific enolase, NeuN, neurofilament-M, and tau. With an optimal differentiation protocol, almost 80% of the cells expressed NSE and NF-M. The refractile cell bodies extended long processes terminating in typical growth cones and filopodia. The differentiating cells expressed nestin, characteristic of neuronal precursor stem cells, at 5 hr, but the trait was undetectable at 6 days. In contrast, expression of trkA, the nerve growth factor receptor, persisted from 5 hr through 6 days. Clonal cell lines, established from single cells, proliferated, yielding both undifferentiated and neuronal cells. Human marrow stromal cells subjected to this protocol also differentiated into neurons. Consequently, adult marrow stromal cells can be induced to overcome their mesenchymal commitment and may constitute an abundant and accessible cellular reservoir for the treatment of a variety of neurologic diseases. Copyright 2000 Wiley-Liss, Inc.
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              Transplantation of embryonic dopamine neurons for severe Parkinson's disease.

              C Freed, P Greene, R Breeze … (2001)
              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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                Author and article information

                Journal
                Journal ID (nlm-ta): Med J Islam Repub Iran
                Journal ID (iso-abbrev): Med J Islam Repub Iran
                Journal ID (publisher-id): MJIRI
                Journal ID (publisher-id): Med J Islam Repub Iran
                Title: Medical Journal of the Islamic Republic of Iran
                Publisher: Iran University of Medical Sciences
                ISSN (Print): 1016-1430
                ISSN (Electronic): 2251-6840
                Publication date Collection: 2015
                Publication date (Electronic): 28 January 2015
                Volume: 29
                Page: 168
                Affiliations
                1 MSc, Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, School of Nursing and Midwifery, Iran University of Medical Sciences, Tehran, Iran. goudarzi.p@ 123456iums.ac.ir
                2 MD, PhD, Chronic Diseases Research Center, Endocrinology and Metabolism Research Institute & Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran. hr_aghayan@ 123456farabi.tums.ac.ir
                3 MD, Endocrinology and Metabolism Research Center , Endocrinology and Metabolism Research Institute, Tehran University of Medical sciences, Tehran, Iran. Larijanib@ 123456tums.ac.ir
                4 PhD, Hematology Department, Faculty of Medicine, Tarbiat Modares University, Tehran, Iran. soleim_m@ 123456modares.ac.ir
                5 PhD, Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. dehpour@ 123456yahoo.com
                6 BSc, Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran. mehrsahebjam44@ 123456gmail.com
                7 BSc, Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran. firozehghaderi@ 123456yahoo.com
                8 MD, PhD, GMP-Compliant Stem Cell Facility, Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute & Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Shariati Hospital, North Kargar, Tehran, Iran. b_arjmand@ 123456farabi.tums.ac.ir
                Author notes
                (Corresponding author) MD, PhD, GMP-Compliant Stem Cell Facility, Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute & Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Shariati Hospital, North Kargar, Tehran, Iran. b_arjmand@ 123456farabi.tums.ac.ir
                Article
                PMC ID: 4431356
                PubMed ID: 26000262
                SO-VID: 7699c34b-fd65-4e73-a4d0-793a34d15a31
                Copyright © © 2015 Iran University of Medical Sciences
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0), which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

                History
                Date received : 22 May 2013
                Date accepted : 21 April 2014
                Page count
                Tables: 1, References: 89, Pages: 10
                Categories
                Subject: Review Article

                Keywords: cellular therapy,neurodegenerative diseases,parkinson’s disease,stem cell
                Data availability:
                Keywords: cellular therapy, neurodegenerative diseases, parkinson’s disease, stem cell

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