Stem cell grafting in parkinsonism – Why, how and when

Munter, Johannes P.J.M. de; Melamed, Eldad; Wolters, Erik Ch.

doi:10.1016/s1353-8020(13)70036-1

Cited by 21 publications

(11 citation statements)

References 29 publications

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“…In this study, we tested the hypothesis that genome modification can be used to eliminate mutant transcripts and nuclear RNA foci in DM1 stem cells. Neural stem cells (NSCs) derived from DM1 iPS cells were chosen for this study because: (a) the CNS of patients with DM1 exhibits molecular, cellular, magnetic resonance imaging, and neuropsychological abnormalities ; (b) frontal executive dysfunction in adults and mental retardation in congenital and child‐onset DM1 are some of the most disabling phenotypes of this multisystemic disease ; (c) technologies for cell transfer therapy in the central nervous system have shown promising recent advances (see recent reviews) ; (d) 100% of the NSCs are nuclear RNA foci positive and are amenable to single cell cloning so that the effect of gene correction can be tracked by monitoring nuclear RNA foci. Our approach was to introduce Simian virus 40 (SV40) and bovine growth hormone (bGH) polyA signals (PASs) upstream of the DMPK CTG expansion using homologous recombination (HR) mediated by a pair of site‐specific transcription activator‐like effector nucleases (TALEN).…”

Section: Introductionmentioning

confidence: 99%

Genome Modification Leads to Phenotype Reversal in Human Myotonic Dystrophy Type 1 Induced Pluripotent Stem Cell-Derived Neural Stem Cells

Xia

Gao

Jin³

et al. 2015

Stem Cells

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Objective Myotonic dystrophy type 1 (DM1) is caused by expanded CTG repeats in the 3'-untranslated region (3’ UTR) of the DMPK gene. Correcting the mutation in DM1 stem cells would be an important step towards autologous stem cell therapy. The objective of this study is to demonstrate in vitro genome editing to prevent production of toxic mutant transcripts and reverse phenotypes in DM1 stem cells. Methods Genome editing was performed in DM1 neural stem cells (NSCs) derived from human DM1 iPS cells. An editing cassette containing SV40/bGH polyA signals was integrated upstream of the CTG repeats by TALEN-mediated homologous recombination (HR). The expression of mutant CUG repeats transcript was monitored by nuclear RNA foci, the molecular hallmarks of DM1, using RNA fluorescence in situ hybridization (RNA-FISH). Alternative splicing of microtubule-associated protein tau (MAPT) and muscleblind-like (MBNL) proteins were analyzed to further monitor the phenotype reversal after genome modification. Results The cassette was successfully inserted into DMPK intron 9 and this genomic modification led to complete disappearance of nuclear RNA foci. MAPT and MBNL 1, 2 aberrant splicing in DM1 NSCs was reversed to normal pattern in genome-modified NSCs. Interpretation Genome modification by integration of exogenous polyA signals upstream of the DMPK CTG repeat expansion prevents the production of toxic RNA and leads to phenotype reversal in human DM1 iPS-cells derived stem cells. Our data provide proof-of-principle evidence that genome modification may be used to generate genetically modified progenitor cells as a first step toward autologous cell transfer therapy for DM1.

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Section: Introductionmentioning

confidence: 99%

Genome Modification Leads to Phenotype Reversal in Human Myotonic Dystrophy Type 1 Induced Pluripotent Stem Cell-Derived Neural Stem Cells

Xia

Gao

Jin³

et al. 2015

Stem Cells

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“…Delivery of molecular and cellular therapeutics through opening of the BBB has the potential to be both safer and more effective than the current method in both humans and experimental animals of intracerebral needle injection. A major limitation of this approach in the case of cell-based therapy for PD is the poor migration of stem cells from the injection site into the large and unfavorable environment of the adult human brain [119][120][121][122]. Although inefficient, opening the BBB allows the cells to be widely distributed throughout the target region using the brains natural route of delivery-the microvasculature.…”

Section: Fus-enhanced Delivery: Opening the Bbbmentioning

confidence: 99%

Focused Ultrasound: An Emerging Therapeutic Modality for Neurologic Disease

Fishman

Frenkel

2017

Neurotherapeutics

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Therapeutic ultrasound is only beginning to be applied to neurologic conditions, but the potential of this modality for a wide spectrum of brain applications is high. Engineering advances now allow sound waves to be targeted through the skull to a brain region selected with real time magnetic resonance imaging and thermography, using a commercial array of focused emitters. High intensities of sonic energy can create a coagulation lesion similar to that of older radiofrequency stereotactic methods, but without opening the skull. This has led to the recent Food and Drug Administration approval of focused ultrasound (FUS) thalamotomy for unilateral treatment of essential tremor. Clinical studies of stereotactic FUS for aspects of Parkinson's disease, chronic pain, and refractory psychiatric indications are underway, with promising results. Moderate-intensity FUS has the potential to safely open the blood-brain barrier for localized delivery of therapeutics, while low levels of sonic energy can be used as a form of neuromodulation.

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“…Neural progenitor cells (NPCs) which were derived from subventricular zone (SVZ) of adult rats transplanted into a rat QA model of HD the results revealed increased motor functions, but NPCs which are derived from embryonic stem cells (ESCs) found to be superior in survival & differentiation than NPCs rom SVZ [110].…”

Section: Neural Progenitor Cells (Npcs)mentioning

confidence: 99%

“…Adipose Derived Stem Cells: There are multiple studies use adipose derived stem cells (ADSc) in animal models of HD, direct transplantation of ADSc in YAC128 transgenic mice have showed secretion of growth factors which prevent apoptosis & improve behavior in the mice [110]. In another studies, instead of direct transplantation of ADSc, Maucksch, C et al intraperitoneal injection in R6/2 animals also showed improvement in behavior & striatal atrophy [111].…”

Section: Neural Progenitor Cells (Npcs)mentioning

confidence: 99%

Stem Cells for Neuro-regeneration: State of the Art

Wagih¹,

Elhawary²,

Ellessy³

et al. 2015

BIO

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Neuroregeneration (NR) is a long-sought medical dream which has intrigued vast research in the past decades. A traditional physiologic dogma that central nervous system does not regenerate has been strongly challenged in the recent years since the advent of the stem cell era. Stem cell research in the regenerative field passes through three main stages. The first stage is the in-vitro experiments which studies the exact molecular and cellular mechanisms underlying stem cell-mediated NR. The second stage is the application of these data in experimental animal settings to provide "proof of concept" of stem cell therapy in animal models. The final step is the translation of these data in pilot clinical trials. In this review, we will try to gather the different data of stem cell-mediated NR from various experimental and clinical researches.

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Stem cell grafting in parkinsonism – Why, how and when

Cited by 21 publications

References 29 publications

Genome Modification Leads to Phenotype Reversal in Human Myotonic Dystrophy Type 1 Induced Pluripotent Stem Cell-Derived Neural Stem Cells

Genome Modification Leads to Phenotype Reversal in Human Myotonic Dystrophy Type 1 Induced Pluripotent Stem Cell-Derived Neural Stem Cells

Focused Ultrasound: An Emerging Therapeutic Modality for Neurologic Disease

Stem Cells for Neuro-regeneration: State of the Art

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