Protection of dopamine neurons by bone marrow stromal cells

Shintani, Aki; Nakao, Naoyuki; Kakishita, Koji; Itakura, Toru

doi:10.1016/j.brainres.2007.09.086

Cited by 39 publications

(43 citation statements)

References 54 publications

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“…In addition, transplantation of human neural SC cloned by v-myc gene transfer receptors (NGFR) and high-affinity trk receptors and they secrete various growth factors, such as GDNF, (HB1.F3 cells) in 6-OHDA-lesioned rats exerted neuroprotective effects against DA depletion by trophic factor BDNF, bFGF, nerve growth factor (NGF), hepatocyte growth factor, vascular endothelial growth factor secretion and neuronal differentiation (73). The SB623 cells appeared to protect or stimulate regeneration in (VEGF), neurotrophin-3 and 4 (NT-3, NT-4) [ (18,24,26,34,54,63), and unpublished data]. Moreover, it has been host DA neurons rather than providing stem cell-derived DA neurons because there was no evidence of TH-ir reported that human MSC can respond to a neuronal tissue environment with both neurotrophin protein release human cells in graft sites.…”

Section: Facing Pagementioning

confidence: 99%

Reversal of Dopaminergic Degeneration in a Parkinsonian Rat following Micrografting of Human Bone Marrow-Derived Neural Progenitors

et al. 2009

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Parkinson's disease (PD) is a common neurodegenerative disease characterized by the selective loss of dopaminergic (DA) neurons in the midbrain. Various types of stem cells that have potential to differentiate into DA neurons are being investigated as cellular therapies for PD. Stem cells also secrete growth factors and therefore also may have therapeutic effects in promoting the health of diseased DA neurons in the PD brain. To address this possibility in an experimental model of PD, bone marrow-derived neuroprogenitor-like cells were generated from bone marrow procured from healthy human adult volunteers and their potential to elicit recovery of damaged DA axons was studied in a partial lesion rat model of PD. Following collection of bone marrow, mesenchymal stem cells (MSC) were isolated and then genetically modified to create SB623 cells by transient transfection with the intracellular domain of the Notch1 gene (NICD), a modification that upregulates expression of certain neuroprogenitor markers. Ten deposits of 0.5 µl of SB623 cell suspension adjusted from 6,000 to 21,000 cells/µl in PBS or PBS alone were stereotaxically placed in the striatum 1 week after the nigrostriatal projection had been partially lesioned in adult F344 rats by injection of 6-hydroxydopamine (6-OHDA) into the striatum. At 3 weeks, a small number of grafted SB623 cells survived in the lesioned striatum as visualized by expression of the human specific nuclear matrix protein (hNuMA). In rats that received SB623 cells, but not in control rats, dense tyrosine hydroxylase immunoreactive (TH-ir) fibers were observed around the grafts. These fibers appeared to be rejuvenated host DA axons because no TH-ir in soma of surviving SB623 cells or coexpression of TH and hNuMA-ir were observed. In addition, dense serotonin immunoreactive (5-HT-ir) fibers were observed around grafted SB623 cells and these fibers also appeared to be of the host origin. Also, in some SB623 grafted rats that were sacrificed within 2 h of dl-amphetamine injection, hot spots of c-Fos-positive nuclei that coincided with rejuvenated dense TH fibers around the grafted SB623 cells were observed, suggesting increased availability of DA in these locations. Our observations suggest that NICD-transfected MSC hold potential as a readily available autologous or allogenic cellular therapy for ameliorating the degeneration of DA and 5-HT neurons in PD patients.

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Section: Facing Pagementioning

confidence: 99%

Reversal of Dopaminergic Degeneration in a Parkinsonian Rat following Micrografting of Human Bone Marrow-Derived Neural Progenitors

et al. 2009

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“…Treatment with MSC-conditioned medium also increased the survival of embryonic mesencephalic dopaminergic neurons in in vitro neuronal injury models of serum deprivation and exposure to 6-OHDA [231]. Furthermore, marked protection was demonstrated when conditioned medium from astrocyte-like, neurotrophic factor-secreting MSCs or undifferentiated MSCs were applied to neuroblastoma cell line, SH-SY5Y, one hour prior to exposure to neurotoxin 6-OHDA [233].…”

Section: Potential Mechanisms Of Functional Improvement Following Mscmentioning

confidence: 89%

“…[231][232][233], or in neural co-culture systems in vitro [231,233,234]. BDNF, GDNF and FGF-2 have been found to be released by murine MSCs into culture media, and treatment of embryonic dopaminergic neurons with conditioned medium prior to transplantation yielded significantly enhanced graft survival and more rapid behavioral recovery of hemiparkinsonian rats [231]. A different strategy has also been employed in which hMSCs were directed toward an astrocytelike, neurotrophic factor-secreting phenotype [232,233].…”

Section: Potential Mechanisms Of Functional Improvement Following Mscmentioning

confidence: 99%

“…Detection of BDNF, GDNF, FGF-2 and FGF-8 expression in vitro by undifferentiated and neuronal-differentiated MSCs, suggested that neurotrophic factor secretion could be the mechanism behind recovery [217]. [231][232][233], or in neural co-culture systems in vitro [231,233,234]. BDNF, GDNF and FGF-2 have been found to be released by murine MSCs into culture media, and treatment of embryonic dopaminergic neurons with conditioned medium prior to transplantation yielded significantly enhanced graft survival and more rapid behavioral recovery of hemiparkinsonian rats [231].…”

Section: Potential Mechanisms Of Functional Improvement Following Mscmentioning

confidence: 99%

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Mesenchymal Stem Cell-Based Therapies for Parkinson’s Disease: Progress, Controversies and Lessons for the Future

Khoo¹,

Tao²,

D.F.³

2011

J Stem Cell Res Ther

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Scientific and clinical research interest in mesenchymal stem cells (MSCs) has increased exponentially since the identification of MSCs in the bone marrow. It is now recognized that MSCs possess the in vitro characteristics of stem cells with the abilities to proliferate, symmetrically divide, and produce multi-lineage mesodermal derivatives, making MSCs attractive candidates for use in potential cellular therapies. Furthermore, MSCs can be relatively easily isolated and expanded in culture with low tumorigenicity and teratoma formation, and have been reported to display immunomodulatory properties that may be advantageous in clinical transplantation. Discovery of the ability of MSCs to differentiate into cells of non-mesodermal tissues, particularly neural cells, has also raised the possibility of utilizing MSCs in regenerative and reparative therapies for neurological disorders. However, a number of hurdles remain to be resolved, including conflicting findings concerning the capacity of MSCs to suppress immune responses and contribute to multiple tissue lineages, highlighting the need for a greater understanding of mechanisms underlying the observed phenomena. In this review we will discuss: (1) recent advances in our understanding of MSC plasticity/transdifferentiation and immunomodulatory properties; (2) evidence for cell-based therapies, in particular MSC-based therapies for Parkinson's disease; and (3) current challenges and potential strategies for the utilization of MSCs in the treatment of Parkinson's disease.

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“…The authors reported successful transfer and expression of the TH gene in the rat striatum, as well as clinical improvement . Experimental studies have shown that MSCs conditioned medium promotes the survival of grafted xenogeneic dopaminergic neurons in affected mice (Shintani et al 2007). Another study using MSCs intravenously showed a significant decrease in the loss of dopaminergic neurons in rats treated with MG-132, which causes a neurodegenerative disease similar to PD (Park et al 2008).…”

Section: Parkinson's Diseasementioning

confidence: 99%

Mesenchymal stem cells for the treatment of neurodegenerative and psychiatric disorders

Colpo¹,

Ascoli

Wollenhaupt-Aguiar

et al. 2015

An. Acad. Bras. Ciênc.

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Mesenchymal stem cells (MSCs) are multipotent progenitor cells that have the capacity to differentiate into all lineages of mesodermal origin, e.g., cartilage, bone, and adipocytes. MSCs have been identified at different stages of development, including adulthood, and in different tissues, such as bone marrow, adipose tissue and umbilical cord. Recent studies have shown that MSCs have the ability to migrate to injured sites. In this regard, an important characteristic of MSCs is their immunomodulatory and antiinflammatory effects. For instance, there is evidence that MSCs can regulate the immune system by inhibiting proliferation of T and B cells. Clinical interest in the use of MSCs has increased considerably over the past few years, especially because of the ideal characteristics of these cells for regenerative medicine. Therapies with MSCs have shown promising results neurodegenerative diseases, in addition to regulating inflammation, they can promote other beneficial effects, such as neuronal growth, decrease free radicals, and reduce apoptosis. Notwithstanding, despite the vast amount of research into MSCs in neurodegenerative diseases, the mechanism of action of MSCs are still not completely clarified, hindering the development of effective treatments. Conversely, studies in models of psychiatric disorders are scarce, despite the promising results of MSCs therapies in this field as well.

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Protection of dopamine neurons by bone marrow stromal cells

Cited by 39 publications

References 54 publications

Reversal of Dopaminergic Degeneration in a Parkinsonian Rat following Micrografting of Human Bone Marrow-Derived Neural Progenitors

Reversal of Dopaminergic Degeneration in a Parkinsonian Rat following Micrografting of Human Bone Marrow-Derived Neural Progenitors

Mesenchymal Stem Cell-Based Therapies for Parkinson’s Disease: Progress, Controversies and Lessons for the Future

Mesenchymal stem cells for the treatment of neurodegenerative and psychiatric disorders

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