Mesenchymal stem cells as therapeutic agents and potential targeted gene delivery vehicle for brain diseases

Huang, Bing; Tabata, Yasuhiko; J, Gao

doi:10.1016/j.jconrel.2012.07.034

Cited by 64 publications

(45 citation statements)

References 121 publications

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“…Mesenchymal stem cells (MSCs) have received much interest regarding cell therapeutic approaches to treat neurological diseases because these cells are readily available for autologous cell therapy [1][2][3]. Several models of brain diseases have been investigated as potential targets including ischemic stroke, various neurodegenerative diseases, and brain tumors.…”

Section: Introductionmentioning

confidence: 99%

Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential

Lojewski

Srimasorn

Rauh

et al. 2015

Stem Cells Translational Medicine

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Brain perivascular cells have recently been identified as a novel mesodermal cell type in the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and, to a lesser extent, tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell therapy in many neurological disorders; therefore, it is of importance to better understand the "intrinsic" MSC population of the human brain. We systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells with fetal and adult human brain-derived neural stem cells (NSCs) and adult human bone marrowderived MSCs. We found that adult human brain pericytes, which can be isolated from the hippocampus and from subcortical white matter, are-in contrast to adult human NSCs-easily expandable in monolayer cultures and show many similarities to human bone marrow-derived MSCs both regarding both surface marker expression and after whole transcriptome profile. Human brain pericytes showed a negligible propensity for neuroectodermal differentiation under various differentiation conditions but efficiently generated mesodermal progeny. Consequently, human brain pericytes resemble bone marrow-derived MSCs and might be very interesting for possible autologous and endogenous stem cell-based treatment strategies and cell therapeutic approaches for treating neurological diseases. STEM CELLS

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Section: Introductionmentioning

confidence: 99%

Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential

Lojewski

Srimasorn

Rauh

et al. 2015

Stem Cells Translational Medicine

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“…Neurogenic differentiation of bone marrow (BM) mesenchymal stem cells (MSCs) offers a new hope for patients with many neurological disorders such as Alzheimer's disease, spinal cord injury, and Parkinson's disease (Huang et al, 2012). The interest in studying this multipotent cell population largely derives from its advantages (Friedenstein et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Comparative study of neural differentiation of bone marrow mesenchymal stem cells by different induction methods

Zhao

2015

Genet. Mol. Res.

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ABSTRACT. Neurogenic differentiation of bone marrow (BM) mesenchymal stem cells (MSCs) offers a new hope for patients with many neurological disorders. Several chemical inducers are employed to induce BMMSCs differentiation into nerve cells. In the present study, we compared different inducers [2-mercaptoethanol (BME), tretinoin (ATRA), dimethyl sulfoxide/ butylated hydroxyanisole (DMSO/BHA), and indomethacin/3-isobutyl-1-methylxanthine (indomethacin/IBMX)] on the neurogenic differentiation of BMMSCs and aimed to identify a more efficient and safer method. The MSCs were first identified by their ability to adhere to plastic and by the expression of positive (CD44, CD90, and CD105) and negative (CD34) markers assessed by flow cytometry. The efficiency of the neurogenic differentiation was determined by assessing the mRNA and protein expression of nestin, microtubule-associated protein-2 (MAP2), neuron specific enolase (NSE), and glial fibrillary acidic protein (GFAP) by reverse transcription-polymerase chain reaction and western-blot, respectively. The effect of these inducers on cell viability was also evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. This comprehensive study shows that indomethacin/IBMX is better than BME, DMSO/BHA, and ATRA both in terms of efficiency and safety, while BME suppressed the growth and proliferation of MSCs.

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“…MSCs are multipotent, capable of differentiating into cells of mesodermal lineage, and display considerable plasticity, differentiating/transdifferentiating into neuronal and glial lineages with the appropriate induction paradigms 17,18 . Furthermore, MSCs have been transplanted and proven effective in preclinical studies for a number of disorders, including neurodegenerative conditions 19 . The therapeutic efficacy of MSCs is well known due to their beneficial anti-proliferative, anti-inflammatory and anti-apoptotic activities 20 .…”

Section: Discussionmentioning

confidence: 99%

High Throughput Characterization of Adult Stem Cells Engineered for Delivery of Therapeutic Factors for Neuroprotective Strategies

Sharma

Brodskiy

Petersen

et al. 2015

JoVE

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Mesenchymal stem cells (MSCs) derived from bone marrow are a powerful cellular resource and have been used in numerous studies as potential candidates to develop strategies for treating a variety of diseases. The purpose of this study was to develop and characterize MSCs as cellular vehicles engineered for delivery of therapeutic factors as part of a neuroprotective strategy for rescuing the damaged or diseased nervous system. In this study we used mouse MSCs that were genetically modified using lentiviral vectors, which encoded brain-derived neurotrophic factor (BDNF) or glial cell-derived neurotrophic factor (GDNF), together with green fluorescent protein (GFP).Before proceeding with in vivo transplant studies it was important to characterize the engineered cells to determine whether or not the genetic modification altered aspects of normal cell behavior. Different culture substrates were examined for their ability to support cell adhesion, proliferation, survival, and cell migration of the four subpopulations of engineered MSCs. High content screening (HCS) was conducted and image analysis performed.Substrates examined included: poly-L-lysine, fibronectin, collagen type I, laminin, entactin-collagen IV-laminin (ECL). Ki67 immunolabeling was used to investigate cell proliferation and Propidium Iodide staining was used to investigate cell viability. Time-lapse imaging was conducted using a transmitted light/environmental chamber system on the high content screening system. Our results demonstrated that the different subpopulations of the genetically modified MSCs displayed similar behaviors that were in general comparable to that of the original, non-modified MSCs. The influence of different culture substrates on cell growth and cell migration was not dramatically different between groups comparing the different MSC subtypes, as well as culture substrates.This study provides an experimental strategy to rapidly characterize engineered stem cells and their behaviors before their application in longterm in vivo transplant studies for nervous system rescue and repair.

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Mesenchymal stem cells as therapeutic agents and potential targeted gene delivery vehicle for brain diseases

Cited by 64 publications

References 121 publications

Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential

Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential

Comparative study of neural differentiation of bone marrow mesenchymal stem cells by different induction methods

High Throughput Characterization of Adult Stem Cells Engineered for Delivery of Therapeutic Factors for Neuroprotective Strategies

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