Cell therapy in Parkinson’s disease

Wallenberg Neuroscience Center and Lund Strategic Center for Stem Cell Biology and Cell Therapy, BMC A11, SE-221 84 Lund, Sweden.
NeuroRx 11/2004; 1(4):382-93. DOI: 10.1602/neurorx.1.4.382
Source: PubMed

ABSTRACT The clinical studies with intrastriatal transplants of fetal mesencephalic tissue in Parkinson's disease (PD) patients have provided proof-of-principle for the cell replacement strategy in this disorder. The grafted dopaminergic neurons can reinnervate the denervated striatum, restore regulated dopamine (DA) release and movement-related frontal cortical activation, and give rise to significant symptomatic relief. In the most successful cases, patients have been able to withdraw L-dopa treatment after transplantation and resume an independent life. However, there are currently several problems linked to the use of fetal tissue: 1) lack of sufficient amounts of tissue for transplantation in a large number of patients, 2) variability of functional outcome with some patients showing major improvement and others modest if any clinical benefit, and 3) occurrence of troublesome dyskinesias in a significant proportion of patients after transplantation. Thus, neural transplantation is still at an experimental stage in PD. For the development of a clinically useful cell therapy, we need to define better criteria for patient selection and how graft placement should be optimized in each patient. We also need to explore in more detail the importance for functional outcome of the dissection and cellular composition of the graft tissue as well as of immunological mechanisms. Strategies to prevent the development of dyskinesias after grafting have to be developed. Finally, we need to generate large numbers of viable DA neurons in preparations that are standardized and quality controlled. The stem cell technology may provide a virtually unlimited source of DA neurons, but several scientific issues need to be addressed before stem cell-based therapies can be tested in PD patients.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Context: Parkinson's disease (PD) is one of the common neurodegenerative disorders, characterized by the gradual loss of dopamine (DA) containing neurons in the substantia nigra. It is currently treated by L-DOPA and DAergic drugs. Although these treatments are very effective in the beginning of the disease, but they are not curative and have side effects in chronic use. Evidence Acquisitions: The aim of cell replacement therapies for PD is looking for a long-lasting relief of patients' symptoms. Different sources of stem cells are recruited to establish a long lasting treatment for PD. We have categorized them into embryonic stem cells from the fertilized egg, neural stem cells from the embryonic or adult brain, mesenchymal stem cell, and stem cells from other tissues. In this review we used three key words "Parkinson's disease, stem cells and neostriatum transplantation" to search in "PubMed" search engine. We found more than hundreds of publications but limitation for citation led us to select only those that were more innovative. Results: Cell replacement therapies in PD aim to provide greater long-lasting relief of patients' symptoms. Although the transplants
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Parkinson's disease (PD) is a neurological disorder characterized by the loss of midbrain dopaminergic (DA) neurons. Neural stem cells (NSCs) are multipotent stem cells that are capable of differentiating into different neuronal and glial elements. The production of DA neurons from NSCs could potentially alleviate behavioral deficits in Parkinsonian patients; timely intervention with NSCs might provide a therapeutic strategy for PD. We have isolated and generated highly enriched cultures of neural stem/progenitor cells from the human olfactory bulb (OB). If NSCs can be obtained from OB, it would alleviate ethical concerns associated with the use of embryonic tissue, and provide an easily accessible cell source that would preclude the need for invasive brain surgery. Following isolation and culture, olfactory bulb neural stem cells (OBNSCs) were genetically engineered to express hNGF and GFP. The hNFGGFP-OBNSCs were transplanted into the striatum of 6-hydroxydopamin (6-OHDA) Parkinsonian rats. The grafted cells survived in the lesion environment for more than eight weeks after implantation with no tumor formation. The grafted cells differentiated in vivo into oligodendrocyte-like (25±2.88%), neuron-like (52.63±4.16%), and astrocyte -like (22.36±1.56%) lineages, which we differentiated based on morphological and immunohistochemical criteria. Transplanted rats exhibited a significant partial correction in stepping and placing in nonpharmacological behavioral tests, pole and rotarod tests. Taken together, our data encourage further investigations of the possible use of OBNSCs as a promising cell-based therapeutic strategy for Parkinson's disease. This article is protected by copyright. All rights reserved
    Journal of Cellular Physiology 12/2014; 230(7). DOI:10.1002/jcp.24909 · 3.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the past two decades, regenerative therapies using stem cell technologies have been developed for various neurological diseases. Although stem cell therapy is an attractive option to reverse neural tissue damage and to recover neurological deficits, it is still under development so as not to show significant treatment effects in clinical settings. In this review, we discuss the scientific and clinical basics of adult neural stem cells (aNSCs), and their current developmental status as cell therapeutics for neurological disease. Compared with other types of stem cells, aNSCs have clinical advantages, such as limited proliferation, inborn differentiation potential into functional neural cells, and no ethical issues. In spite of the merits of aNSCs, difficulties in the isolation from the normal brain, and in the in vitro expansion, have blocked preclinical and clinical study using aNSCs. However, several groups have recently developed novel techniques to isolate and expand aNSCs from normal adult brains, and showed successful applications of aNSCs to neurological diseases. With new technologies for aNSCs and their clinical strengths, previous hurdles in stem cell therapies for neurological diseases could be overcome, to realize clinically efficacious regenerative stem cell therapeutics.


Available from