Human umbilical cord mesenchymal stem cells derived from Wharton's jelly differentiate into cholinergic-like neurons in vitro

Liang, Jun; Wu, Shan; Zhao, Hui; Li, Shulei; Liu, Zhixin; Wu, Jiang; Zhou, Li

doi:10.1016/j.neulet.2012.11.014

Cited by 38 publications

(29 citation statements)

References 31 publications

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“…The discovery that MSCs derived from both mouse and human origins can be manipulated to differentiate into functional neurons encouraged the use of MSCs‐derived neuronal cell types for the replacement of damaged neural tissue. Emerging protocols have used specific culture conditions for ex vivo differentiation of human MSCs into dopamine‐secreting and acetylcholine (Ach)‐secreting neuronal‐like cells. Alternatively, superior similarity to original neuronal subtypes was reported through the genetic modification‐mediated transdifferentiation of human bone marrow‐derived MSCs (hBM‐MSCs) using ectopic expression of neuronal subtype‐specific transcription factors .…”

Section: Induction Of Neuronal Regenerationmentioning

confidence: 99%

Concise Review: Mesenchymal Stem Cells in Neurodegenerative Diseases

2017

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Stem cell-based therapies for neurodegenerative diseases aim at halting clinical deterioration by regeneration and by providing local support for damaged tissue. Mesenchymal stem cells (MSCs) hold great potential for cell therapy as they can be efficiently derived from adult tissue, ex vivo expanded in culture and safely transplanted autologously. MSCs were also shown to be able to differentiate toward neural fates and to secrete a broad range of factors able to promote nervous tissue maintenance and repair. Moreover, upon transplantation, MSCs were shown capable of homing toward lesioned areas, implying their potential use as vehicles for therapeutic agents administration. Indeed, various advantageous effects were reported following human MSCs transplantation into rodent models of neurodegenerative diseases, such as neurotrophic factormediated protection, enhanced neurogenesis, modulation of inflammation, and abnormal protein aggregate clearance. Recent studies have also used ex vivo manipulation for enhanced expression of potentially favorable factors, by so exploiting the homing capacity of MSCs for effective expression at the lesion site. Here, we will summarize current advancements in MSCs-based therapies for neurodegenerative diseases. We will examine the roles of central mechanisms suggested to mediate the beneficial effects of MSCs-based therapy and consider the augmentation of these mechanisms for superior clinical outcomes in rodent models of neurodegeneration as well as in clinical trials. STEM CELLS 2017;35:1867-1880 SIGNIFICANCE STATEMENTMesenchymal stem cells (MSCs) hold great potential as source for cell-based therapy for neurodegenerative diseases. In this review, we summarize recent progress using human MSC transplantation into rodent models of neurodegeneration. We examine the molecular mechanisms mediating disease amelioration through this approach and emphasize the potential of ex vivo manipulation for these cells before transplantation.

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Section: Induction Of Neuronal Regenerationmentioning

confidence: 99%

Concise Review: Mesenchymal Stem Cells in Neurodegenerative Diseases

2017

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“…It has been postulated that BM-MSCs constitutively expressed genes related to immunomodulation, adipose tissue derived-MSCs highly expressed genes implicated in tissue development [14], whereas the transcriptome profiling of WJ-MSCs revealed an increased expression of genes involved in liver development [66] and an inherent bias towards the neuro-ectoderm lineage [14,67]. These observations suggest that WJ-MSCs might be better cell candidates for differentiation into hepatocyte and neuronal rather than endothelial phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Isolation method and xeno-free culture conditions influence multipotent differentiation capacity of human Wharton’s jelly-derived mesenchymal stem cells

et al. 2013

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IntroductionHuman Wharton’s jelly (WJ) has become a preferred source of mesenchymal stem cells (MSCs) whose clinical applications are limited by the use of adequate xeno-free (XF), in vitro manipulation conditions. Therefore, the objective of our study was to characterize WJ-derived MSCs (WJ-MSCs), isolated by different methods and cultured in a commercially available, MSC XF medium, not least of all by investigating their endothelial differentiation capacity.MethodsWJ explants and enzymatically dissociated WJ cells were cultured in a defined, XF medium for MSCs. Adherent cells at passages 2 and 5 were characterized as MSCs by flow cytometry, MTT, real-time quantitative reverse transcription PCR, and functional multipotent differentiation assays. The endothelial differentiation capacity of MSCs isolated and expanded until passage 2 in the MSC XF medium, and then subcultured for five passages in a commercially available endothelial growth medium (group A), was assessed over serial passages, as compared to adherent WJ-derived cells isolated and expanded for five consecutive passages in the endothelial medium (group B).ResultsThe MSC phenotype of WJ explant- and pellet-derived cells, isolated and expanded in the MSC XF medium, was proven based on the expression of CD44/CD73/CD90/CD105 surface markers and osteo-/adipo-/chondrogenic multipotent differentiation potential, which differed according to the isolation method and/or passage number. Upon exposure to endothelial differentiation cues, cells belonging to group A did not exhibit endothelial cell characteristics over serial passages; by contrast, WJ pellet-derived cells belonging to group B expressed endothelial characteristics at gene, protein and functional levels, potentially due to culture conditions favoring the isolation of other stem/progenitor cell types than MSCs, able to give rise to an endothelial progeny.ConclusionsThe use of defined, MSC XF media for isolation and expansion of human WJ-MSCs is a prerequisite for the establishment of their real endothelial differentiation capacity, as candidates for clinical therapy applications. Thus, the standardization of WJ-MSCs isolation and culture expansion techniques in defined, MSC XF media, for their accurate characterization, would be a priority in the stem cell research field.

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“…The acetylcholine concentration was measured in the supernatant of induction medium using a previously described protocol [1]. Briefly, an aliquot of culture supernatant was collected from the cholinergic neuronal differentiated dishes, and the concentration of acetylcholine was measured using Amplex ® RED Acetylcholine/Acetylcholinesterase Assay kit (Invitrogen TM , ThermoFisher Scientific, Waltham, MA, USA) according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

“…Cholinergic neurons have pivotal roles in cognition, locomotion, and behavioral response, which predominantly use the neurotransmitter, acetylcholine (Ach), for their message delivery [1,2]. The loss of cholinergic neurons results in the reduction of choline acetyltransferase (ChAT) activity, leading to the absence of Ach, which results in motor nerve degeneration, as well as irreversible cognitive decline, as observed in Alzheimer’s disease [3].…”

Section: Introductionmentioning

confidence: 99%

Cholinergic Nerve Differentiation of Mesenchymal Stem Cells Derived from Long-Term Cryopreserved Human Dental Pulp In Vitro and Analysis of Their Motor Nerve Regeneration Potential In Vivo

Jang

Kang

Ullah

et al. 2018

IJMS

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The reduction of choline acetyltransferase, caused by the loss of cholinergic neurons, leads to the absence of acetylcholine (Ach), which is related to motor nerve degeneration. The aims of the present study were to evaluate the in vitro cholinergic nerve differentiation potential of mesenchymal stem cells from cryopreserved human dental pulp (hDPSCs-cryo) and to analyze the scale of in vivo motor nerve regeneration. The hDPSCs-cryo were isolated and cultured from cryopreserved dental pulp tissues, and thereafter differentiated into cholinergic neurons using tricyclodecane-9-yl-xanthogenate (D609). Differentiated cholinergic neurons (DF-chN) were transplanted into rats to address sciatic nerve defects, and the scale of in vivo motor nerve regeneration was analyzed. During in vitro differentiation, the cells showed neuron-like morphological changes including axonal fibers and neuron body development, and revealed high expression of cholinergic neuron-specific markers at both the messenger RNA (mRNA) and protein levels. Importantly, DF-chN showed significant Ach secretion ability. At eight weeks after DF-chN transplantation in rats with sciatic nerve defects, notably increased behavioral activities were detected with an open-field test, with enhanced low-affinity nerve growth factor receptor (p75NGFR) expression detected using immunohistochemistry. These results demonstrate that stem cells from cryopreserved dental pulp can successfully differentiate into cholinergic neurons in vitro and enhance motor nerve regeneration when transplanted in vivo. Additionally, this study suggests that long-term preservation of dental pulp tissue is worthwhile for use as an autologous cell resource in the field of nerve regeneration, including cholinergic nerves.

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Human umbilical cord mesenchymal stem cells derived from Wharton's jelly differentiate into cholinergic-like neurons in vitro

Cited by 38 publications

References 31 publications

Concise Review: Mesenchymal Stem Cells in Neurodegenerative Diseases

Concise Review: Mesenchymal Stem Cells in Neurodegenerative Diseases

Isolation method and xeno-free culture conditions influence multipotent differentiation capacity of human Wharton’s jelly-derived mesenchymal stem cells

Cholinergic Nerve Differentiation of Mesenchymal Stem Cells Derived from Long-Term Cryopreserved Human Dental Pulp In Vitro and Analysis of Their Motor Nerve Regeneration Potential In Vivo

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