Elsevier

Translational Research

Volume 156, Issue 3, September 2010, Pages 155-160
Translational Research

Review Article
Translation of stem cell therapy for neurological diseases

https://doi.org/10.1016/j.trsl.2010.07.002Get rights and content

“Regenerative medicine” hopefully will provide novel therapies for diseases that remain without effective therapy. This development is also true for most neurodegenerative disorders including Alzheimer’s disease, Huntington’s disease, or Parkinson’s disease. Transplantation of new neurons to the brain has been performed in Parkinson’s disease and in Huntington’s disease. The restoration of dopaminergic neurons in patients with Parkinson’s disease via implantation of embryonic midbrain tissue was taken from animal experiments to clinical applications, showing a limited efficacy. Clinical trials in patients with Huntington’s disease using fetal striatal tissue currently are underway. Today, it seems possible to generate functional dopaminergic or striatal neurons form a variety of stem cells including embryonic or neural stem cells as well as induced pluripotent stem cells. First clinical trials using neural stem cell or embryonic-stem-cell-derived tissue are approved or already underway. Such cells allow for extensive in vitro and in vivo testing as well as “good manufacturing production,” reducing the risks in clinical application.

Section snippets

Embryonic Stem Cells

ESCs are considered pluripotent because they result in all cells in the body. They can be expanded for many years and differentiated into neural stem or precursor cells and subsequently into brain cells.6, 7, 8, 9, 10 Because PD can be considered a model disease for cell replacement resulting from the limited number of primarily affected neurons and existing proof of principle, the generation of pure populations of dopaminergic neurons was of paramount interest. Here, genetic manipulations seem

Induced Pluripotent Stem Cells

When Yamanaka and Takahashi first discovered that it is possible to reprogram adult somatic cells so that they acquire characteristics very similar to ESCs, it was considered the main breakthrough in regenerative medicine.16 Initial reprogramming required retroviral transfer into fibroblasts of 4 transcription factors (ie, c-myc, oct4, klf2, and sox2). Subsequently, other research groups demonstrated that fewer factors may suffice for individual cell types and that adenoviral gene transfer or

Neural Stem Cells

NSCs can be extracted directly from fetal or adult nervous tissue via the dissection and digestion of brain regions of interest. Several serum-free and serum-containing growth media allow the proliferation of such cells when supplemented with appropriate mitogens such as epidermal growth factor (EGF) and basic fibroblast growth factor (FGF-2).

NSCs derived from embryonic or fetal central nervous tissue generate oligodendrocytes, neurons, and astrocytes in an approximate ratio of 1:5:25,

Mesenchymal Stem Cells

Bone-marrow-derived stem cells comprising mesenchymal stem cells have been applied to patients with hematological malignancies and other disorders for many years. Mesenchymal or bone-marrow-derived stem cells also provide the advantage of minimizing immune reactions because these can be derived from the respective patient. Many optimistic reports have been made about transdifferentiation or conversion of mesenchymal stem cell into NSCs or neurons. But the proof of functional neurons derived

Conclusions

Developing stem cell technology represents a prime research interest. Analyzing such cells in vitro and in vivo will help to understand neuronal development in many species including humans. The translation toward clinical transplantation of stem or progenitor cells currently is restricted to NSCs as long as well-documented trials are concerned. The use of bone-marrow-derived stem cells is applied broadly outside of clinical trials and is far away from having demonstrated safety or efficacy.

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