Preconditioning mesenchymal stem cells with the mood stabilizers lithium and valproic acid enhances therapeutic efficacy in a mouse model of Huntington's disease

Linares, Gabriel; Chiu, Chi‐Tso; Scheuing, Lisa; Leng, Yan; Liao, Hsiao‐Mei; Maric, Dragan; Chuang, De‐Maw

doi:10.1016/j.expneurol.2016.04.003

Cited by 63 publications

(68 citation statements)

References 52 publications

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“…These MSCs exhibited intragenic effects such as an enhanced expression of antioxidants, migration-related genes, and anti-apoptosis molecules. This level of gene expression profile was not seen when using unpreconditioned cells (75).…”

Section: Huntington's Diseasementioning

confidence: 77%

“…Pharmacological and clinical drugs: Mesenchymal stem cell-based therapy is a great choice for treating CNS diseases, although loss of the cells after transplantations remains a serious setback. Exposure of MSCs to different pharmacological agents is another preconditioning method for strengthening their survival when they encounter the harsh microenvironment of the damaged tissue (75,76). Atorvastatin (C33H35FN2O5), a lipid-lowering statin, commonly used to prevent cardiovascular-related diseases.…”

Section: Pretreatment (Preconditioning) Of Mscsmentioning

confidence: 99%

“…Lithium and valproic acid (VPA)-preconditioned MSCs indicate enhanced expression of different genes like antioxidant, anti-apoptosis, and migration-related genes. The increased expression of these genes causes augmented survival of MSCs following transplantation (75).…”

Section: Pretreatment (Preconditioning) Of Mscsmentioning

confidence: 99%

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Manipulated Mesenchymal Stem Cells Applications in Neurodegenerative Diseases

Sadatpoor

Salehi

Rahban

et al. 2020

IJSC

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Mesenchymal stem cells (MSCs) are multipotent stem cells that have multilinear differentiation and self-renewal abilities. These cells are immune-privileged as they express no or low level of class-II major histocompatibility complex (MHC-II) and other costimulatory molecules. Having neuroprotective and regenerative properties, MSCs can be used to ameliorate several intractable neurodegenerative disorders by affecting both innate and adaptive immune systems. Several manipulations like pretreating MSCs with different conditions or agents, and using molecules derived from MSCs or genetically manipulating them, are the common and practical ways that can be used to strengthen MSCs survival and potency. Improved MSCs can have significantly enhanced impacts on diseases compared to MSCs not manipulated. In this review, we describe some of the most important manipulations that have been exerted on MSCs to improve their therapeutic functions and their applications in ameliorating three prevalent neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and Huntington's disease.

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Section: Huntington's Diseasementioning

confidence: 77%

Section: Pretreatment (Preconditioning) Of Mscsmentioning

confidence: 99%

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Manipulated Mesenchymal Stem Cells Applications in Neurodegenerative Diseases

Sadatpoor

Salehi

Rahban

et al. 2020

IJSC

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“…IND of stem-cell-based therapeutics takes advantage of stem cells’ natural tropism toward glioma and their capacity to administer multiple therapeutic modalities in a repeatable and minimally invasive course. Once the modality is fully understood, it may be used in the treatment of different brain malignancies or other brain disorders [2,15,31,124–126]. …”

Section: Expert Opinionmentioning

confidence: 99%

Intranasal delivery of stem cell-based therapies for the treatment of brain malignancies

Bonamici

Dey

et al. 2017

Expert Opinion on Drug Delivery

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Introduction Glioblastoma (GBM) is the most aggressive malignant brain cancer in adults, and its poor prognosis and resistance to the existing standard of care require the development of innovative therapeutic modalities. The local delivery of stem cells as therapeutic carriers against glioma has produced encouraging results, but encounters obstacles with regards to the repeatability and invasiveness of administration. Intranasal delivery of therapeutic stem cells could overcome these obstacles, among others, as a noninvasive and easily repeatable mode of administration. Areas covered This review describes nasal anatomy, routes of stem cell migration, and factors affecting stem cell delivery to hard-to-reach tumors. Furthermore, this review discusses the molecular mechanisms underlying stem cell migration following delivery, as well as possible stem cell effector functions to be considered in combination with intranasal delivery. Expert opinion Further research is necessary to elucidate the dynamics of stem cell effector functions in the context of intranasal delivery and optimize their therapeutic potency. Nonetheless, the technique represents a promising tool against brain cancer and has the potential to be expanded for use against other brain pathologies.

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“…Pretreating MSCs with a combination of hematopoietic growth factors erythropoietin (EPO) and granulocyte colony stimulating factor (G-CSF) can enhance their motility by increasing the MMP expression [78] . Tsai et al showed that priming with valproate and/or lithium resulted into robust migration and homing of the MSCs towards the sites of ischemia in models of stroke and Huntington's disease [79,80] . The underlying mechanism may involve an increase in CXCR4 expression by histone deacetylase (HDAC) inhibition, or elevation in MMP-9 levels through glycogen synthase kinase-3β inhibition.…”

Section: Pretreatment Of Mscs With Cytokines and Small Moleculesmentioning

confidence: 99%

Strategies to improve the migration of mesenchymal stromal cells in cell therapy

Chen

et al. 2017

Transl. Neurosci. Clin.

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KEYWORDSMSCs; migration; cell therapy; engraftment efficiency; neurological disorder Mesenchymal stromal/stem cells (MSCs) are multipotent cells under consideration as a potential new therapy for a variety of inflammatory diseases including certain neurological disorders. It is generally thought that the efficacy of cell therapy in attenuating damage after ischemia, inflammation, or injury depends on the quantity of transplanted cells recruited to the target tissue. However, only a small number of systematically infused MSCs can effectively migrate to target sites, which significantly decreases the efficacy of exogenous cell-based therapy. In this review, we discuss specific factors influencing MSC migration, and summarize current strategies that effectively promote the motility of MSCs. In addition, we describe several protocols to improve the migration of stromal cells into the nervous system and, therefore, enhance the efficiency of engraftment as means of treating neurological disorders.Citation Li G, Hu Y, Chen Y, Tang Z. Strategies to improve the migration of mesenchymal stromal cells in cell therapy. Transl. Neurosci. Clin. 2017, 3(3): 159-175.

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Preconditioning mesenchymal stem cells with the mood stabilizers lithium and valproic acid enhances therapeutic efficacy in a mouse model of Huntington's disease

Cited by 63 publications

References 52 publications

Manipulated Mesenchymal Stem Cells Applications in Neurodegenerative Diseases

Manipulated Mesenchymal Stem Cells Applications in Neurodegenerative Diseases

Intranasal delivery of stem cell-based therapies for the treatment of brain malignancies

Strategies to improve the migration of mesenchymal stromal cells in cell therapy

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