Differentiation of adult bone marrow stem cells into neuroprogenitor cells in vitro

Kim, Byoung J; Seo, Jeong Hyun; Bubien, James K.; Oh, Young S.

doi:10.1097/00001756-200207020-00023

Cited by 149 publications

(88 citation statements)

References 19 publications

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“…Results from the present study demonstrated that some MSCs differentiated into excitable neuronal-like cells. Previous studies have confirmed that MSCs can be induced to express neural markers and exhibit a neuronal appearance under specific induction conditions [4][5][6][7][8]. However, a normal mature neuron is not only defined by these characteristics, but more importantly by electrophysiological properties and functional activity.…”

Section: Discussionmentioning

confidence: 93%

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Induction-dependent neural marker expression and electrophysiological characteristics of bone marrow mesenchymal stem cells that naturally express high levels of nestin

Liu

Wang

et al. 2011

Chin. Sci. Bull.

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Under certain experimental conditions, bone marrow mesenchymal stem cells (MSCs) express neuronal phenotypes and neuronal markers, which suggests that they could be used to treat various neurological diseases. In the present study, MSCs were isolated from adult rat bone marrow, cultivated, and evaluated for neurotrophin expression profiles, as well as the potential to differentiate into functional neuronal-like cells in vitro. MSCs from passage 5 were pre-induced with DMEM/F12 medium containing 10% fetal bovine serum (FBS) and 10 ng/mL bFGF (fibroblast growth factor-2). Subsequently, a chemical inductor containing Dimethyl Sulphoxide (DMSO), Butylated Hydroxyanisole (BHA) and forskolin were used to induce neural expression of MSCs.Expression patterns of nestin, NF-200, and GFAP at time points before and after induction were detected by immunofluorescence.Nerve Growth Factor (NGF), brain-derived neurotrophic factor (BDNF) expressions in MSCs were evaluated by RT-PCR.The whole-cell patch clamp technique was utilized to elucidate the electrical behavior of MSC before and after 24-h differentiation induction. Immunofluorescence analysis revealed that MSCs expressed nestin (57.1% ± 6.9%), but not NF-200 or GFAP. Following neural induction, the cells exhibited a neuronal-like appearance. Nestin and NF-200 expression was positive in the neuronal-like cells, but GFAP expression was negative. After 6-, 12-and 24-h induction, the ratio of nestin-positive cells was 96.5% ± 1.9%, 88.1% ± 5.4%, and 33.5% ± 5.4%. NF-200 positive cells were 90.1% ± 2.9%, 97.5% ± 1.3%, and 98.1% ± 1.6%, respectively. However, prior to induction, MSCs already expressed NGF and BDNF. With a stimulus impulse of 40 mV, the density of the transient outward K current was (9.95 ± 4.85) pA/pF (n = 9) and (328.50 ± 30.62) pA/pF (n = 9) before and after induction, and the density of transient calcium ion currents was (-0.059 ± 0.027) pA/pF (n = 7) and (-6.66 ± 0.50) pA/pF (n = 7), respectively. Transient outward potassium currents and calcium ions currents gradually increased following induction. In addition, MSCs isolated from bone marrow exhibited characteristics of neuronal progenitor cells and expressed neurotrophins. These cells exhibited the capacity to differentiate into functional neuronal-like cells in vitro. These results suggested that MSCs express high levels of nestin and could be utilized for therapeutic strategies to treat nervous system diseases.

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Section: Discussionmentioning

confidence: 93%

“…In particular, MSCs have been reported to differentiate into neural cells in vitro [4][5][6][7][8] through the use of various chemical inductors, as well as in vivo following implanta-tion into the brain and spinal cord [9][10][11][12][13][14]. However, differentiation under chemical induction, or in combination with cytokines, should be reconsidered.…”

mentioning

confidence: 99%

Induction-dependent neural marker expression and electrophysiological characteristics of bone marrow mesenchymal stem cells that naturally express high levels of nestin

Liu

Wang

et al. 2011

Chin. Sci. Bull.

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“…Many studies demonstrated the differentiation of human and mice MSCs to neuron-like cells following induction with BME, DMSO and BHA [34]- [40], which exhibited a neuron-like morphology for few hours after induction which is due to a breakdown of the actin cytoskeleton and a retraction of the cell edge [40]. Since BHA also contains the sulfhydryl group, it may be deduced that the neuron-like morphology adopted by the exposed mouse MSCs has the same mechanism and could be due to the disruption of F-actin and cytoskeleton reorganization.…”

Section: Discussionmentioning

confidence: 99%

Production of Neural Progenitors from Bone Marrow Mesenchymal Stem Cells

Mohammad¹,

Yaseen²,

Al-Joubory³

et al. 2016

SCD

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In the brain, there are hundreds of types of specialized neurons and to generate one type of them we need to have neural progenitors for differentiation to specific neuron type. Mesenchymal stem cells (MSCs) are easily isolated, cultured, manipulated ex vivo, showing great potential for therapeutic applications. The adult MSCs have the potential to produce progeny that differentiate into a variety of cell types such as neurons. This fact suggests that MSCs derived neurons are an important cell type and a deep understanding of the molecular characteristics of it would significantly enhance the advancement of cell therapy for neurological disorders. Therefore, in this study, we isolated, identified, and studied neural progenitors by measuring expression levels through neurogenesis pathway of three neural differentiation markers nestin (NES), neurofilament (NF-L), and microtubule association protein (MAP-2) from mouse bone marrow MSCs (mouse bmMSCs) by using butylated hydroxyanisole (BHA) and diethyl sulfoxide (DMSO) as neural inducers agents. The results of immunocytochemistry and Real Time-PCR showed that in contrast to MSCs, neural differentiated cells showed neural progenitor pattern by showing stable increase in NES gene expression through differentiation process with increasing the protein expression through different exposures times, while NF-L gene and protein expression start to increased after 48 h but not replaced the NES expression completely even when its expression passed NES levels. The maturation marker Map-2 expression was low during the duration of differentiation period in protein and gene expression, which prove that these cells are still progenitors and can be redirected into specific type of neurons by further treatments. * Corresponding authors. M. Mohammad et al.2

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“…Original reports that bone marrow cells could differentiate towards Purkinje neurons were challenged by others, reporting that these cells were the result of fusion of donor cells with endogenous Purkinje neurons (Alvarez-Dolado et al, 2003;Weimann et al, 2003b). Next to these in vivo studies, several in vitro studies have shown that stem cells could be isolated out of bone marrow and that these stem cells were capable of transdifferentiation towards neural-like cells (Woodbury et al, 2000;SanchezRamos et al, 2000;Kohyama et al, 2001;Deng et al, 2001;Kabos et al, 2002;Jiang et al, 2003Jiang et al, , 2002Kim et al, 2002;Munoz-Elias et al, 2003;Rismanchi et al, 2003;Levy et al, 2003;Locatelli et al, 2003;Padovan et al, 2003;Dezawa et al, 2004;Tondreau et al, 2004;Magaki et al, 2005;Bossolasco et al, 2005). In some of these studies, bone marrow-derived cells were even capable of differentiation towards cells of the three different germinal layers (endoderm, mesoderm and ectoderm).…”

Section: Introductionmentioning

confidence: 99%

Differentiation assays of bone marrow-derived Multipotent Adult Progenitor Cell (MAPC)-like cells towards neural cells cannot depend on morphology and a limited set of neural markers

Raedt

Pinxteren

Dycke

et al. 2007

Experimental Neurology

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There are accumulating studies that report a neurogenic potential of bone marrow-derived cells both in vitro as well as in vivo. Most claims of neural "transdifferentiation" have based their conclusions on morphology and neural gene expression. Recently, doubts have been raised about the validity of both outcome parameters since non-neural cells can extend neurites and show aberrant neural gene expression as a response to stress inducing factors. In this study, we compared bone marrow-derived Multipotent Adult Progenitor Cell (MAPC)-like cells and neural stem cells (NSC) in their morphology and neural gene expression profile after neural differentiation using three differentiation protocols. We evaluated the expression of five neuroglial antigens [neurofilament 200 (NF200); beta III tubulin (β3 tub); tau; Glial Fibrillary Acidic Protein (GFAP); Myelin Basic Protein (MBP) and RIP antigen] using real-time PCR (RT-PCR) and immunocytochemistry (ICC). MAPC-like cells adopted a neural-like morphology in one protocol but a fibroblast-like morphology in the two other protocols. RT-PCR and ICC show that MAPC-like cells already express the neural antigens beta III tubulin and NF200 at baseline, but no upregulation of these genes after exposure to three distinct differentiation protocols was seen. In contrast, NSC adopt neural and glial morphologies with a clear increase in expression of all neuroglial genes in all differentiation protocols used. In conclusion, our data demonstrate that neural-like morphology and expression of a limited set of neural marker genes by MAPC-like cells after differentiation are not absolute proof of neural transdifferentiation because MAPC-like cells only partially meet the criteria which are fulfilled by NSC after neural differentiation.

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Differentiation of adult bone marrow stem cells into neuroprogenitor cells in vitro

Cited by 149 publications

References 19 publications

Induction-dependent neural marker expression and electrophysiological characteristics of bone marrow mesenchymal stem cells that naturally express high levels of nestin

Induction-dependent neural marker expression and electrophysiological characteristics of bone marrow mesenchymal stem cells that naturally express high levels of nestin

Production of Neural Progenitors from Bone Marrow Mesenchymal Stem Cells

Differentiation assays of bone marrow-derived Multipotent Adult Progenitor Cell (MAPC)-like cells towards neural cells cannot depend on morphology and a limited set of neural markers

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