Analysis of neuron-like differentiation of human bone marrow mesenchymal stem cells

Choi, Chang Rak; Cho, Yun Kyoung; Prakash, Kulkarni; Jee, Bo Keun; Han, Chang Whan; Paik, Young Ki; Kim, Hwi Yool; Lee, Kweon Haeng; Chung, Namhyun; Rha, Hyoung Kyun

doi:10.1016/j.bbrc.2006.09.010

Cited by 53 publications

(41 citation statements)

References 23 publications

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“…Besides, similar immature action potentials and current-voltage relationships are often observed for developing human neurons [26] and neuron-like cells differentiated from stem cells isolated from humans [14,25,28,30,37,47,48] or from rodents [29,32,33,49,50]. Finally, consistent with those previously published studies [9,[11][12][13][14]25,47,48,[51][52][53][54], we confirmed that neuron-like cells with neuronal morphology usually express neuronal and not glial markers (Fig. 1A).…”

Section: Membrane Properties Of Neuron-like Cells Differentiated Fromsupporting

confidence: 91%

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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Section: Membrane Properties Of Neuron-like Cells Differentiated Fromsupporting

confidence: 91%

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

View full text Add to dashboard Cite

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“…However, several neural cell-related mRNAs and proteins are also expressed by undifferentiated MSCs (75). Moreover, several studies have shown that in vitro neuronal differentiation protocols using chemical induction medium can produce unexpected and misleading effects, such as changes in cell morphology due to actin cytoskeleton disruption, cell shrinkage, or toxicity (76)(77)(78)(79) and the transient upregulation of neural markers without the induction of neural differentiation (80). These reports indicate the need for a more cautious evaluation of MSC differentiation that distinguishes between molecular signaling and lineage commitment steps to reliably assess the ability of MSCs to differentiate into neural cells.…”

Section: Differentiation Into Neural Cells In Vitromentioning

confidence: 99%

Transplantation of umbilical cord–derived mesenchymal stem cells as a novel strategy to protect the central nervous system: technical aspects, preclinical studies, and clinical perspectives

2012

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“…With the differentiation of MSCs into neuron‐like cells, the expression of FN was concomitantly and progressively decreased. This may be a possible result of switching of the cell type from mesodermal to ectodermal due to a decreased expression of mesoderm gene in cells undergoing neural differentiation 46, 47. Although RT‐PCR showed an obvious reduction in FN expression, the amount of FN protein within the scaffold increased with time.…”

Section: Discussionmentioning

confidence: 99%

Autocrine fibronectin from differentiating mesenchymal stem cells induces the neurite elongationin vitroand promotes nerve fiber regeneration in transected spinal cord injury

Zeng

Chen

et al. 2016

J. Biomed. Mater. Res.

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Extracellular matrix (ECM) expression is temporally and spatially regulated during the development of stem cells. We reported previously that fibronectin (FN) secreted by bone marrow mesenchymal stem cells (MSCs) was deposited on the surface of gelatin sponge (GS) soon after culture. In this study, we aimed to assess the function of accumulated FN on neuronal differentiating MSCs as induced by Schwann cells (SCs) in three dimensional transwell co‐culture system. The expression pattern and amount of FN of differentiating MSCs was examined by immunofluorescence, Western blot and immunoelectron microscopy. The results showed that FN accumulated inside GS scaffold, although its mRNA expression in MSCs was progressively decreased during neural induction. MSC‐derived neuron‐like cells showed spindle‐shaped cell body and long extending processes on FN‐decorated scaffold surface. However, after blocking of FN function by application of monoclonal antibodies, neuron‐like cells showed flattened cell body with short and thick neurites, together with decreased expression of integrin β1. In vivo transplantation study revealed that autocrine FN significantly facilitated endogenous nerve fiber regeneration in spinal cord transection model. Taken together, the present results showed that FN secreted by MSCs in the early stage accumulated on the GS scaffold and promoted the neurite elongation of neuronal differentiating MSCs as well as nerve fiber regeneration after spinal cord injury. This suggests that autocrine FN has a dynamic influence on MSCs in a three dimensional culture system and its potential application for treatment of traumatic spinal cord injury. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1902–1911, 2016.

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Analysis of neuron-like differentiation of human bone marrow mesenchymal stem cells

Cited by 53 publications

References 23 publications

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

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

Transplantation of umbilical cord–derived mesenchymal stem cells as a novel strategy to protect the central nervous system: technical aspects, preclinical studies, and clinical perspectives

Autocrine fibronectin from differentiating mesenchymal stem cells induces the neurite elongationin vitroand promotes nerve fiber regeneration in transected spinal cord injury

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