Critical issues of clinical human embryonic stem cell therapy for brain repair

Li, Jia Yi; Christophersen, Nicolaj S.; Hall, Vanessa Jane; Soulet, Denis; Brundin, Patrik

doi:10.1016/j.tins.2007.12.001

Cited by 177 publications

(139 citation statements)

References 66 publications

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“…Although later double-blind placebo-controlled trials reported no significant clinical benefits (38,39), successful cell replacement therapy in PD would probably be achieved with more sophisticated cell preparation, surgical and patient selection procedures (2,3). In particular, optimization of cell preparation has been an issue when using fetal tissue because of its limited availability and accessibility; thus, there is an urgent need to develop alternative cell sources (40). In addition, recent basic studies based on fetal tissue graft systems have suggested several potential refinements.…”

Section: Discussionmentioning

confidence: 99%

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Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques

et al. 2012

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Section: Discussionmentioning

confidence: 99%

“…Others have also suggested that expression of DATs in the graft cells alleviates dyskinesias after graft (41). Therefore, proof-of-concept studies using fetal tissue grafts have established the direction of cell-based therapies, including those using stem cells (2,3,40). Particular concerns when…”

Section: Discussionmentioning

confidence: 99%

Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques

et al. 2012

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“…Yet, technical difficulties isolating neural stem cells (NSCs) and ethical concerns, among other issues, have limited the use of embryonic stem cells in clinical settings [1,2]. For example, transplanted embryonic stem cells can cause immune reactions and tumors that can damage healthy tissue [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

“…For example, transplanted embryonic stem cells can cause immune reactions and tumors that can damage healthy tissue [3][4][5]. In addition, the techniques that are traditionally used to grow and differentiate embryonic stem cells for therapeutic applications, cocultures with feeder cells, and=or a medium containing animal products are potentially harmful [1]. The ideal stem cell for clinical use would be isolated from the patient's own tissue.…”

Section: Introductionmentioning

confidence: 99%

“…This direct induction of MeSCs to differentiate into neuronal-and glial-like phenotypes usually involves exposure to growth factors, potentially toxic chemical agents, and cocultures with neural cells. In addition, the survival of terminally differentiated neuron-and glia-like cells after transplantation into the CNS is often poor [1,19]. The survival of undifferentiated embryonic stem cells is better, but very few differentiate into neurons that integrate into the brain or spinal cord, and the risk for tumor formation increases [17,[20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

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Membrane Properties of Neuron-Like Cells Generated from Adult Human Bone-Marrow-Derived Mesenchymal Stem Cells

Fox

Shen

et al. 2010

Stem Cells and Development

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Adult mesenchymal stem cells (MeSCs) isolated from human bone marrow are capable of generating neural stem cell (NSC)-like cells that can be subsequently differentiated into cells expressing molecular markers for neurons. Here we report that these neuron-like cells had functional properties similar to those of brain-derived neurons. Whole-cell patch-clamp recordings and calcium imaging experiments were performed on neuron-like cells differentiated from bone-marrow-derived NSC-like cells. The neuron-like cells were subjected to current pulses to determine if they were capable of generating depolarization-induced action potentials. We found that nearly all of the cells with neuron-like morphology exhibited active membrane properties in response to the depolarizing pulses. The most common response was a single spike-like event with an overshoot and brief afterhyperpolarization. Cells that did not generate overshooting spike-like events usually displayed rectifying current-voltage relationships. The prevalence of these active membrane properties in response to the depolarizing current pulses suggested that the human MeSCs (hMeSCs) were capable of converting to a neural lineage under defined culture conditions. The spike-like events were blocked by the voltage-gated sodium channel inhibitor lidocaine, but unaffected by another sodium channel inhibitor tetrodotoxin (TTX). In calcium imaging experiments, the neuron-like cells responded to potassium chloride depolarization and l-glutamate application with increases in the cytoplasmic calcium levels. Thus, the neuron-like cells appeared to express TTX-resistant voltage-gated sodium channels, voltage-gated calcium channels, and functional l-glutamate receptors. These results demonstrate that hMeSCs were capable of generating cells with characteristics typical of functional neurons that may prove useful for neuroreplacement therapies.

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Tissue Engineering Biomaterials

Peter

Eyster

Doleyres

2018

Encyclopedia of Polymer Science and Technology

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Tissue engineering has shown great promise in developing novel therapies for treating injured tissue and organ failure. Scaffolds play a pivotal role in tissue engineering. Biodegradable polymers are the primary choice of material for tissue engineering scaffolds, due to their numerous advantageous properties. In this article, the principles of tissue engineering are discussed in relation to polymer science and engineering. The most frequently used polymers in tissue engineering are briefly reviewed. These include synthetic and natural polymers commonly used in constructing both porous and hydrogel scaffolds. Their structure and critical properties in relation to scaffold function are discussed in depth, along with a detailed review of the important roles functionalized materials and controlled release play in tissue engineering. Important polymer processing techniques in the context of scaffold fabrication are also reviewed. These include the textile technologies, electrospinning, particulate‐leaching techniques, phase‐separation techniques, rapid prototyping, and other novel three‐dimensional (3D) fabrication techniques. In this update, the impact of pluripotent stem cells, conductive polymers, controlled drug release, 3D printing, and nanofibrous topology on tissue engineering are also discussed.

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Critical issues of clinical human embryonic stem cell therapy for brain repair

Cited by 177 publications

References 66 publications

Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques

Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques

Membrane Properties of Neuron-Like Cells Generated from Adult Human Bone-Marrow-Derived Mesenchymal Stem Cells

Tissue Engineering Biomaterials

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