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Stem cell therapy and curcumin synergistically enhance recovery from spinal cord injury.

Ormond DR, Shannon C, Oppenheim J, Zeman R, Das K, Murali R, Jhanwar-Uniyal M - PLoS ONE (2014)

Bottom Line: Stem cell therapy improved recovery from moderate SCI, however, it had a limited effect on recovery after severe SCI.Curcumin stimulated NSC proliferation in vitro, and in combination with stem cell therapy, induced profound recovery from severe SCI as evidenced by improved functional locomotor recovery, increased body weight, and soleus muscle mass.Furthermore, our results indicate that the effect of curcumin extends beyond its known anti-inflammatory properties to the regulation of stem cell proliferation.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, New York Medical College, Valhalla, New York, United States of America.

ABSTRACT
Acute traumatic spinal cord injury (SCI) is marked by the enhanced production of local cytokines and pro-inflammatory substances that induce gliosis and prevent reinnervation. The transplantation of stem cells is a promising treatment strategy for SCI. In order to facilitate functional recovery, we employed stem cell therapy alone or in combination with curcumin, a naturally-occurring anti-inflammatory component of turmeric (Curcuma longa), which potently inhibits NF-κB. Spinal cord contusion following laminectomy (T9-10) was performed using a weight drop apparatus (10 g over a 12.5 or 25 mm distance, representing moderate or severe SCI, respectively) in Sprague-Dawley rats. Neural stem cells (NSC) were isolated from subventricular zone (SVZ) and transplanted at the site of injury with or without curcumin treatment. Functional recovery was assessed by BBB score and body weight gain measured up to 6 weeks following SCI. At the conclusion of the study, the mass of soleus muscle was correlated with BBB score and body weight. Stem cell therapy improved recovery from moderate SCI, however, it had a limited effect on recovery after severe SCI. Curcumin stimulated NSC proliferation in vitro, and in combination with stem cell therapy, induced profound recovery from severe SCI as evidenced by improved functional locomotor recovery, increased body weight, and soleus muscle mass. These findings demonstrate that curcumin in conjunction with stem cell therapy synergistically improves recovery from severe SCI. Furthermore, our results indicate that the effect of curcumin extends beyond its known anti-inflammatory properties to the regulation of stem cell proliferation.

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Stem cell therapy in conjunction with low-dose curcumin had a synergistic effect in recovery from severe SCI, as demonstrated by improved BBB score.A: Functional analysis (BBB) after moderate SCI showed that stem cell therapy with a high dose of curcumin rendered BBB scores, which were statistically significant as compared to control rats (DMSO), starting from week 3. B: In severe SCI, rats undergoing combined NSC transplantation and curcumin showed consistent improvement in BBB score as compared to DMSO treated controls. Statistical analysis of combined NSC+curcumin treatment also demonstrated significant improvement in comparison to NSC or curcumin treatment alone.
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pone-0088916-g002: Stem cell therapy in conjunction with low-dose curcumin had a synergistic effect in recovery from severe SCI, as demonstrated by improved BBB score.A: Functional analysis (BBB) after moderate SCI showed that stem cell therapy with a high dose of curcumin rendered BBB scores, which were statistically significant as compared to control rats (DMSO), starting from week 3. B: In severe SCI, rats undergoing combined NSC transplantation and curcumin showed consistent improvement in BBB score as compared to DMSO treated controls. Statistical analysis of combined NSC+curcumin treatment also demonstrated significant improvement in comparison to NSC or curcumin treatment alone.

Mentions: Animals undergoing NSC transplant, or with combined treatment using NSC+curcumin, were tested after moderate SCI. Rats treated with NSC transplant demonstrated a significant improvement starting at week three. A significant difference in BBB score between cohorts was seen with the scores of 12.14±0.65 and 9.33±0.99 (p = 0.028) at week five and 12.86±0.93 and 9.67±1.02(p = 0.029) at week six, for NSC treated and control rats, respectively. Combinational treatment with high dose curcumin and NSC transplant significantly improved the BBB score as compared to control. However, between combinational treatment and NSC alone, there was no noticeable difference in improvement based on BBB score (Fig. 2A). Curcumin monotherapy showed significant improvement in recovery from SCI in comparison to control, as we have previously reported [14].


Stem cell therapy and curcumin synergistically enhance recovery from spinal cord injury.

Ormond DR, Shannon C, Oppenheim J, Zeman R, Das K, Murali R, Jhanwar-Uniyal M - PLoS ONE (2014)

Stem cell therapy in conjunction with low-dose curcumin had a synergistic effect in recovery from severe SCI, as demonstrated by improved BBB score.A: Functional analysis (BBB) after moderate SCI showed that stem cell therapy with a high dose of curcumin rendered BBB scores, which were statistically significant as compared to control rats (DMSO), starting from week 3. B: In severe SCI, rats undergoing combined NSC transplantation and curcumin showed consistent improvement in BBB score as compared to DMSO treated controls. Statistical analysis of combined NSC+curcumin treatment also demonstrated significant improvement in comparison to NSC or curcumin treatment alone.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3928327&req=5

pone-0088916-g002: Stem cell therapy in conjunction with low-dose curcumin had a synergistic effect in recovery from severe SCI, as demonstrated by improved BBB score.A: Functional analysis (BBB) after moderate SCI showed that stem cell therapy with a high dose of curcumin rendered BBB scores, which were statistically significant as compared to control rats (DMSO), starting from week 3. B: In severe SCI, rats undergoing combined NSC transplantation and curcumin showed consistent improvement in BBB score as compared to DMSO treated controls. Statistical analysis of combined NSC+curcumin treatment also demonstrated significant improvement in comparison to NSC or curcumin treatment alone.
Mentions: Animals undergoing NSC transplant, or with combined treatment using NSC+curcumin, were tested after moderate SCI. Rats treated with NSC transplant demonstrated a significant improvement starting at week three. A significant difference in BBB score between cohorts was seen with the scores of 12.14±0.65 and 9.33±0.99 (p = 0.028) at week five and 12.86±0.93 and 9.67±1.02(p = 0.029) at week six, for NSC treated and control rats, respectively. Combinational treatment with high dose curcumin and NSC transplant significantly improved the BBB score as compared to control. However, between combinational treatment and NSC alone, there was no noticeable difference in improvement based on BBB score (Fig. 2A). Curcumin monotherapy showed significant improvement in recovery from SCI in comparison to control, as we have previously reported [14].

Bottom Line: Stem cell therapy improved recovery from moderate SCI, however, it had a limited effect on recovery after severe SCI.Curcumin stimulated NSC proliferation in vitro, and in combination with stem cell therapy, induced profound recovery from severe SCI as evidenced by improved functional locomotor recovery, increased body weight, and soleus muscle mass.Furthermore, our results indicate that the effect of curcumin extends beyond its known anti-inflammatory properties to the regulation of stem cell proliferation.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, New York Medical College, Valhalla, New York, United States of America.

ABSTRACT
Acute traumatic spinal cord injury (SCI) is marked by the enhanced production of local cytokines and pro-inflammatory substances that induce gliosis and prevent reinnervation. The transplantation of stem cells is a promising treatment strategy for SCI. In order to facilitate functional recovery, we employed stem cell therapy alone or in combination with curcumin, a naturally-occurring anti-inflammatory component of turmeric (Curcuma longa), which potently inhibits NF-κB. Spinal cord contusion following laminectomy (T9-10) was performed using a weight drop apparatus (10 g over a 12.5 or 25 mm distance, representing moderate or severe SCI, respectively) in Sprague-Dawley rats. Neural stem cells (NSC) were isolated from subventricular zone (SVZ) and transplanted at the site of injury with or without curcumin treatment. Functional recovery was assessed by BBB score and body weight gain measured up to 6 weeks following SCI. At the conclusion of the study, the mass of soleus muscle was correlated with BBB score and body weight. Stem cell therapy improved recovery from moderate SCI, however, it had a limited effect on recovery after severe SCI. Curcumin stimulated NSC proliferation in vitro, and in combination with stem cell therapy, induced profound recovery from severe SCI as evidenced by improved functional locomotor recovery, increased body weight, and soleus muscle mass. These findings demonstrate that curcumin in conjunction with stem cell therapy synergistically improves recovery from severe SCI. Furthermore, our results indicate that the effect of curcumin extends beyond its known anti-inflammatory properties to the regulation of stem cell proliferation.

Show MeSH
Related in: MedlinePlus