Bone marrow stromal cells produce nerve growth factor and glial cell line-derived neurotrophic factors

García, Rocío; Aguiar, Jorge; Alberti, Esteban; Cuetara, Karelys de la; Pavón, Nancy

doi:10.1016/j.bbrc.2004.02.111

Cited by 91 publications

(47 citation statements)

References 5 publications

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“…Therefore, this therapy of cell replacement has the potential of further improving functional deficits, even though the results from clinical trials are still debatable [30,31]. Intriguingly, we observed that delivery of LacZBMSCs also provided certain degree of neuroprotective effects in this research, and are speculating that it is supposedly due to BMSC's ability of synthesizing and releasing a little GDNF [32][33][34]. Nonetheless, GDNF-BMSCs transplantation brought about a significant better outcome than that of LacZ-BMSCs with regard to behavioral test, the TH positive cells in the SNc, and the TH level in SNc in our study, in favor of the value of GDNF-BMSCs strategy.…”

Section: Discussionmentioning

confidence: 52%

Intrastriatal Transplantation of GDNF-engineered BMSCs and its neuroprotection in Lactacystin-induced Parkinsonian Rat Model

Cao

et al. 2009

Neurochem Res

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The potential value of glial cell line-derived neurotrophic factor (GDNF) in treating Parkinson's disease (PD) remains controversial. In order to evaluate the therapeutic effect of GDNF-engineered bone marrow stromal cells (BMSCs) in parkinsonian rat model, GDNF-BMSCs and LacZ-BMSCs were transplanted into striatum and followed by Lactacystin lesioning at median forebrain bundles 1 week later. We observed that the intrastriatal transplantation of GDNF-BMSCs could significantly rescue the dopaminergic neurons from lactacystin-induced neurotoxicity with regard to behavioral recovery, tyrosine hydroxylase level in nigra and striatum, and striatal dopamine level. We interpret the outcomes that intrastriatal transplantation of GDNF-BMSCs might be beneficial in the treatment of PD.

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Section: Discussionmentioning

confidence: 52%

Intrastriatal Transplantation of GDNF-engineered BMSCs and its neuroprotection in Lactacystin-induced Parkinsonian Rat Model

Cao

et al. 2009

Neurochem Res

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“…Considering that GDNF is produced by bone marrow stromal cells as well as osteoblasts (9,44,45), it is tempting to speculate that GDNF in conjunction with other auto-and paracrine factors may be involved in the regulation of osteoblast recruitment in bone growth and remodelling. Indeed, this study demonstrated that GDNF cooperated with the cytokine TNF-α to stimulate osteoblastic cell growth suggesting an interaction between GDNF and TNF-α signalling pathways in osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

Glial cell line-derived neurotrophic factor influences proliferation of osteoblastic cells

2012

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Little is known about the role of neurotrophic growth factors in bone metabolism. This study investigated the short-term effects of glial cell line-derived neurotrophic factor (GDNF) on calvarial-derived MC3T3-E1 osteoblasts. MC3T3-E1 expressed GDNF as well as its canonical receptors, GFR1 and RET. Addition of recombinant GDNF to cultures in serum-containing medium modestly inhibited cell growth at high concentrations; however, under serum-free culture conditions GDNF dose-dependently increased cell proliferation. GDNF effects on cell growth were inversely correlated with its effect on alkaline phosphatase (ALP) activity showing a significant dose-dependent inhibition of relative ALP activity with increasing concentrations of GDNF in serumfree culture medium. Live/dead and lactate dehydrogenase assays demonstrated GDNF did not significantly affect cell death or survival under serum-containing and serum-free conditions. The effect of GDNF on cell growth was abolished in the presence of inhibitors to GFR1 and RET indicating that GDNF stimulated calvarial osteoblasts via 221 its canonical receptors. Finally, this study found that GDNF synergistically increased tumor necrosis factor-α (TNF-α)-stimulated MC3T3-E1 cell growth suggesting that GDNF interacted with TNF-α-induced signaling in osteoblastic cells. In conclusion, this study provides evidence for a direct, receptor-mediated effect of GDNF on osteoblasts highlighting a novel role for GDNF in bone physiology.

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“…Successful outcomes of neural stem cell grafts in restoration of function after 6-OHDA-induced nigrostriatal degeneration has been attributed to a combination of neural differentiation and trophic factor production (Yasuhara, Matsukawa et al 2006) in large part based on the observation that a large fraction of adult neural stem cells within transplanted grafts retain detectable nestin expression and never fully mature post-transplantation. Likewise, the in vivo neuroprotective effects of other cell types with demonstrated in vitro multi-lineage potential, including mesenchymal stem cells (MSC) (Scuteri, Cassetti et al 2006), umbilical cord matrix stem cells (Weiss, Medicetty et al 2006), and bone marrow derived stromal cells (BMSCs) (Garcia, Aguiar et al 2004;Carvey, Chen et al 2005;Ye, Chen et al 2005), has been shown to be mediated in part through a mechanism of trophic support.…”

Section: Discussionmentioning

confidence: 99%

Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson's disease

McCoy

Martinez

Ruhn

et al. 2008

Experimental Neurology

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Adult adipose contains stromal progenitor cells with neurogenic potential. However, the stability of neuronal phenotypes adopted by Adipose-Derived Adult Stromal (ADAS) cells and whether terminal neuronal differentiation is required for their consideration as alternatives in cell replacement strategies to treat neurological disorders is largely unknown. We investigated whether in vitro neural induction of ADAS cells determined their ability to neuroprotect or restore function in a lesioned dopaminergic pathway. In vitro-expanded naïve or differentiated ADAS cells were autologously transplanted into substantia nigra 1-week after an intrastriatal 6-hydroxydopamine injection. Neurochemical and behavioral measures demonstrated neuroprotective effects of both ADAS grafts against 6-hydroxydopamine-induced dopaminergic neuron death, suggesting that pre-transplantation differentiation of the cells does not determine their ability to survive or neuroprotect in vivo. Therefore, we investigated whether equivalent protection by naïve and neurally-induced ADAS grafts resulted from robust in situ differentiation of both graft types into dopaminergic fates. Immunohistological analyses revealed that ADAS cells did not adopt dopaminergic cell fates in situ, consistent with the limited ability of these cells to undergo terminal differentiation into electrically active neurons in vitro. Moreover, re-exposure of neurally-differentiated ADAS cells to serum-containing medium in vitro confirmed ADAS cell phenotypic instability (plasticity). Lastly, given that gene expression analyses of in vitro-expanded ADAS cells revealed that both naïve and differentiated ADAS cells express potent dopaminergic survival factors, ADAS transplants may have exerted neuroprotective effects by production of trophic factors at the lesion site. ADAS cells may be ideal for ex vivo gene transfer therapies in Parkinson's disease treatment.

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Bone marrow stromal cells produce nerve growth factor and glial cell line-derived neurotrophic factors

Cited by 91 publications

References 5 publications

Intrastriatal Transplantation of GDNF-engineered BMSCs and its neuroprotection in Lactacystin-induced Parkinsonian Rat Model

Intrastriatal Transplantation of GDNF-engineered BMSCs and its neuroprotection in Lactacystin-induced Parkinsonian Rat Model

Glial cell line-derived neurotrophic factor influences proliferation of osteoblastic cells

Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson's disease

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