Limits...
Spirulina promotes stem cell genesis and protects against LPS induced declines in neural stem cell proliferation.

Bachstetter AD, Jernberg J, Schlunk A, Vila JL, Hudson C, Cole MJ, Shytle RD, Tan J, Sanberg PR, Sanberg CD, Borlongan C, Kaneko Y, Tajiri N, Gemma C, Bickford PC - PLoS ONE (2010)

Bottom Line: We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress.Quantification of the BrdU positive cells in the subgranular zone of the dentate gyrus demonstrated a decrease in proliferation of the stem/progenitor cells in the hippocampus as a result of the LPS insult.When examined on neural stem cells in culture spirulina increased proliferation at baseline and protected against the negative influence of TNFalpha to reduce neural stem cell proliferation.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pharmacology and Physiology, College of Medicine, University of South Florida, Tampa, Florida, United States of America.

ABSTRACT
Adult stem cells are present in many tissues including, skin, muscle, adipose, bone marrow, and in the brain. Neuroinflammation has been shown to be a potent negative regulator of stem cell and progenitor cell proliferation in the neurogenic regions of the brain. Recently we demonstrated that decreasing a key neuroinflammatory cytokine IL-1beta in the hippocampus of aged rats reversed the age-related cognitive decline and increased neurogenesis in the age rats. We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress. The objectives of this study were to determine if spirulina could protect the proliferative potential of hippocampal neural progenitor cells from an acute systemic inflammatory insult of lipopolysaccharide (LPS). To this end, young rats were fed for 30 days a control diet or a diet supplemented with 0.1% spirulina. On day 28 the rats were given a single i.p. injection of LPS (1 mg/kg). The following day the rats were injected with BrdU (50 mg/kg b.i.d. i.p.) and were sacrificed 24 hours after the first injection of BrdU. Quantification of the BrdU positive cells in the subgranular zone of the dentate gyrus demonstrated a decrease in proliferation of the stem/progenitor cells in the hippocampus as a result of the LPS insult. Furthermore, the diet supplemented with spirulina was able to negate the LPS induced decrease in stem/progenitor cell proliferation. In a second set of studies we examined the effects of spirulina either alone or in combination with a proprietary formulation (NT-020) of blueberry, green tea, vitamin D3 and carnosine on the function of bone marrow and CD34+ cells in vitro. Spirulina had small effects on its own and more than additive effects in combination with NT-020 to promote mitochondrial respiration and/or proliferation of these cells in culture. When examined on neural stem cells in culture spirulina increased proliferation at baseline and protected against the negative influence of TNFalpha to reduce neural stem cell proliferation. These results support the hypothesis that a diet enriched with spirulina and other nutraceuticals may help protect the stem/progenitor cells from insults.

Show MeSH

Related in: MedlinePlus

Spirulina increases proliferation of human hematopoetic stem cells in vitro.(A) The effects of spirulina and NT-020 on the proliferation of human bone marrow cells was examined. Cells were plated in 96 well plates and spirulina at varying concentrations was added to the culture media. In a separate study shown in the same graph the highest dose of spirulina tested alone (125 ng/ml) was added to NT-020. After 72 hours in culture viability was tested using the MTT assay. Data is expressed at % over control, which are cells grown in media only. When spirulina is combined with NT-020 the effect is significantly higher than NT-020 alone was more than additive. (B) The effects of spirulina and NT-020 on the proliferation of human CD34+ cells was examined. Cells were plated in 96 well plates and spirulina at varying doses was added to the culture media, in a separate study shown in the same graph the highest dose of spirulina tested alone (125 ng/ml) was added to NT-020. After 72 hours in culture viability was tested using the MTT assay. Data is expressed at % over control, which is cells grown in media only. When spirulina is combined with NT-020 the effect is significantly higher than NT-020 alone (p<0.05 students 2-tailed t-test) and the effect appears to be additive. ** p<0.001 ***p<0.0001 (compare to control). P<0.0001 (NT-020 vs. spirulina+NT-020).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2864748&req=5

pone-0010496-g006: Spirulina increases proliferation of human hematopoetic stem cells in vitro.(A) The effects of spirulina and NT-020 on the proliferation of human bone marrow cells was examined. Cells were plated in 96 well plates and spirulina at varying concentrations was added to the culture media. In a separate study shown in the same graph the highest dose of spirulina tested alone (125 ng/ml) was added to NT-020. After 72 hours in culture viability was tested using the MTT assay. Data is expressed at % over control, which are cells grown in media only. When spirulina is combined with NT-020 the effect is significantly higher than NT-020 alone was more than additive. (B) The effects of spirulina and NT-020 on the proliferation of human CD34+ cells was examined. Cells were plated in 96 well plates and spirulina at varying doses was added to the culture media, in a separate study shown in the same graph the highest dose of spirulina tested alone (125 ng/ml) was added to NT-020. After 72 hours in culture viability was tested using the MTT assay. Data is expressed at % over control, which is cells grown in media only. When spirulina is combined with NT-020 the effect is significantly higher than NT-020 alone (p<0.05 students 2-tailed t-test) and the effect appears to be additive. ** p<0.001 ***p<0.0001 (compare to control). P<0.0001 (NT-020 vs. spirulina+NT-020).

Mentions: We analyzed the effects of spirulina on human neural progenitor cells and human bone marrow and CD34+ cells in culture to determine if spirulina could have a potentially direct effect on the proliferation of stem cells. Using this assay we previously found that NT-020 could promote proliferation of bone marrow and bone marrow derived CD34+ progenitors and progenitor cells from peripheral blood (CD133+) in vitro [14]. Using this previously validated assay, human bone marrow cells were grown in culture with either spirulina alone, NT-020 alone, or spirulina in combination with NT-020 added to the culture media for 72 hours. A significant effect was found in the bone marrow cells proliferation assay (F(5,35) = 166.8, p<0.0001; Fig 6.A). Replicating previously published results, NT-020 significantly increased proliferation of bone marrow cells (p<0.001; Fig 6A) [14]. Spirulina alone at concentrations of 62 ng/ml (p<0.001) and 125 ng/ml (p<0.001) significantly increased proliferation of bone marrow cells in culture when compared with control conditions without spirulina. When spirulina (125 ng/ml) was combined with NT-020 the combined group was significantly different from NT-020 alone (p<0.001). Moreover the effect on cell proliferation was 50% greater then what would be expected if the increase in proliferation was an additive effect. One caveat to take into consideration when considering these results is that the MTT assay measures mitochondrial function and thus is an indirect measure of proliferation, thus if a primary effect of these treatments is an increase in mitochondrial respiration, then this may exaggerate the conclusion of proliferative effects of this treatment.


Spirulina promotes stem cell genesis and protects against LPS induced declines in neural stem cell proliferation.

Bachstetter AD, Jernberg J, Schlunk A, Vila JL, Hudson C, Cole MJ, Shytle RD, Tan J, Sanberg PR, Sanberg CD, Borlongan C, Kaneko Y, Tajiri N, Gemma C, Bickford PC - PLoS ONE (2010)

Spirulina increases proliferation of human hematopoetic stem cells in vitro.(A) The effects of spirulina and NT-020 on the proliferation of human bone marrow cells was examined. Cells were plated in 96 well plates and spirulina at varying concentrations was added to the culture media. In a separate study shown in the same graph the highest dose of spirulina tested alone (125 ng/ml) was added to NT-020. After 72 hours in culture viability was tested using the MTT assay. Data is expressed at % over control, which are cells grown in media only. When spirulina is combined with NT-020 the effect is significantly higher than NT-020 alone was more than additive. (B) The effects of spirulina and NT-020 on the proliferation of human CD34+ cells was examined. Cells were plated in 96 well plates and spirulina at varying doses was added to the culture media, in a separate study shown in the same graph the highest dose of spirulina tested alone (125 ng/ml) was added to NT-020. After 72 hours in culture viability was tested using the MTT assay. Data is expressed at % over control, which is cells grown in media only. When spirulina is combined with NT-020 the effect is significantly higher than NT-020 alone (p<0.05 students 2-tailed t-test) and the effect appears to be additive. ** p<0.001 ***p<0.0001 (compare to control). P<0.0001 (NT-020 vs. spirulina+NT-020).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2864748&req=5

pone-0010496-g006: Spirulina increases proliferation of human hematopoetic stem cells in vitro.(A) The effects of spirulina and NT-020 on the proliferation of human bone marrow cells was examined. Cells were plated in 96 well plates and spirulina at varying concentrations was added to the culture media. In a separate study shown in the same graph the highest dose of spirulina tested alone (125 ng/ml) was added to NT-020. After 72 hours in culture viability was tested using the MTT assay. Data is expressed at % over control, which are cells grown in media only. When spirulina is combined with NT-020 the effect is significantly higher than NT-020 alone was more than additive. (B) The effects of spirulina and NT-020 on the proliferation of human CD34+ cells was examined. Cells were plated in 96 well plates and spirulina at varying doses was added to the culture media, in a separate study shown in the same graph the highest dose of spirulina tested alone (125 ng/ml) was added to NT-020. After 72 hours in culture viability was tested using the MTT assay. Data is expressed at % over control, which is cells grown in media only. When spirulina is combined with NT-020 the effect is significantly higher than NT-020 alone (p<0.05 students 2-tailed t-test) and the effect appears to be additive. ** p<0.001 ***p<0.0001 (compare to control). P<0.0001 (NT-020 vs. spirulina+NT-020).
Mentions: We analyzed the effects of spirulina on human neural progenitor cells and human bone marrow and CD34+ cells in culture to determine if spirulina could have a potentially direct effect on the proliferation of stem cells. Using this assay we previously found that NT-020 could promote proliferation of bone marrow and bone marrow derived CD34+ progenitors and progenitor cells from peripheral blood (CD133+) in vitro [14]. Using this previously validated assay, human bone marrow cells were grown in culture with either spirulina alone, NT-020 alone, or spirulina in combination with NT-020 added to the culture media for 72 hours. A significant effect was found in the bone marrow cells proliferation assay (F(5,35) = 166.8, p<0.0001; Fig 6.A). Replicating previously published results, NT-020 significantly increased proliferation of bone marrow cells (p<0.001; Fig 6A) [14]. Spirulina alone at concentrations of 62 ng/ml (p<0.001) and 125 ng/ml (p<0.001) significantly increased proliferation of bone marrow cells in culture when compared with control conditions without spirulina. When spirulina (125 ng/ml) was combined with NT-020 the combined group was significantly different from NT-020 alone (p<0.001). Moreover the effect on cell proliferation was 50% greater then what would be expected if the increase in proliferation was an additive effect. One caveat to take into consideration when considering these results is that the MTT assay measures mitochondrial function and thus is an indirect measure of proliferation, thus if a primary effect of these treatments is an increase in mitochondrial respiration, then this may exaggerate the conclusion of proliferative effects of this treatment.

Bottom Line: We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress.Quantification of the BrdU positive cells in the subgranular zone of the dentate gyrus demonstrated a decrease in proliferation of the stem/progenitor cells in the hippocampus as a result of the LPS insult.When examined on neural stem cells in culture spirulina increased proliferation at baseline and protected against the negative influence of TNFalpha to reduce neural stem cell proliferation.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pharmacology and Physiology, College of Medicine, University of South Florida, Tampa, Florida, United States of America.

ABSTRACT
Adult stem cells are present in many tissues including, skin, muscle, adipose, bone marrow, and in the brain. Neuroinflammation has been shown to be a potent negative regulator of stem cell and progenitor cell proliferation in the neurogenic regions of the brain. Recently we demonstrated that decreasing a key neuroinflammatory cytokine IL-1beta in the hippocampus of aged rats reversed the age-related cognitive decline and increased neurogenesis in the age rats. We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress. The objectives of this study were to determine if spirulina could protect the proliferative potential of hippocampal neural progenitor cells from an acute systemic inflammatory insult of lipopolysaccharide (LPS). To this end, young rats were fed for 30 days a control diet or a diet supplemented with 0.1% spirulina. On day 28 the rats were given a single i.p. injection of LPS (1 mg/kg). The following day the rats were injected with BrdU (50 mg/kg b.i.d. i.p.) and were sacrificed 24 hours after the first injection of BrdU. Quantification of the BrdU positive cells in the subgranular zone of the dentate gyrus demonstrated a decrease in proliferation of the stem/progenitor cells in the hippocampus as a result of the LPS insult. Furthermore, the diet supplemented with spirulina was able to negate the LPS induced decrease in stem/progenitor cell proliferation. In a second set of studies we examined the effects of spirulina either alone or in combination with a proprietary formulation (NT-020) of blueberry, green tea, vitamin D3 and carnosine on the function of bone marrow and CD34+ cells in vitro. Spirulina had small effects on its own and more than additive effects in combination with NT-020 to promote mitochondrial respiration and/or proliferation of these cells in culture. When examined on neural stem cells in culture spirulina increased proliferation at baseline and protected against the negative influence of TNFalpha to reduce neural stem cell proliferation. These results support the hypothesis that a diet enriched with spirulina and other nutraceuticals may help protect the stem/progenitor cells from insults.

Show MeSH
Related in: MedlinePlus