Limits...
IGF-1 enhances cell proliferation and survival during early differentiation of mesenchymal stem cells to neural progenitor-like cells.

Huat TJ, Khan AA, Pati S, Mustafa Z, Abdullah JM, Jaafar H - BMC Neurosci (2014)

Bottom Line: To unravel the roles and effects of different growth factors in the differentiation of MSCs into neural lineages, we have differentiated MSCs into neural lineages using different combinations of growth factors.The NPCs derived from IGF-1 treatment also resulted in a better yield after the terminal differentiation into neurons and glial cells than that of the other treated groups.Our results suggested that IGF-1 has a crucial role in the differentiation of MSCs into neuronal lineage by enhancing the proliferation and reducing the apoptosis in the NPCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Jalan Hospital Universiti Sains Malaysia, 16150 Kubang Kerian, Kota Bharu, Kelantan, Malaysia. teejonghuat@gmail.com.

ABSTRACT

Background: There has been increasing interest recently in the plasticity of mesenchymal stem cells (MSCs) and their potential to differentiate into neural lineages. To unravel the roles and effects of different growth factors in the differentiation of MSCs into neural lineages, we have differentiated MSCs into neural lineages using different combinations of growth factors. Based on previous studies of the roles of insulin-like growth factor 1 (IGF-1) in neural stem cell isolation in the laboratory, we hypothesized that IGF-1 can enhance proliferation and reduce apoptosis in neural progenitor-like cells (NPCs) during differentiation of MSCs into NCPs.We induced MSCs differentiation under four different combinations of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, (C) EGF + bFGF + LIF, (D) EGF + bFGF + BDNF, and (E) without growth factors, as a negative control. The neurospheres formed were characterized by immunofluorescence staining against nestin, and the expression was measured by flow cytometry. Cell proliferation and apoptosis were also studied by MTS and Annexin V assay, respectively, at three different time intervals (24 hr, 3 days, and 5 days). The neurospheres formed in the four groups were then terminally differentiated into neuron and glial cells.

Results: The four derived NPCs showed a significantly higher expression of nestin than was shown by the negative control. Among the groups treated with growth factors, NPCs treated with IGF-1 showed the highest expression of nestin. Furthermore, NPCs derived using IGF-1 exhibited the highest cell proliferation and cell survival among the treated groups. The NPCs derived from IGF-1 treatment also resulted in a better yield after the terminal differentiation into neurons and glial cells than that of the other treated groups.

Conclusions: Our results suggested that IGF-1 has a crucial role in the differentiation of MSCs into neuronal lineage by enhancing the proliferation and reducing the apoptosis in the NPCs. This information will be beneficial in the long run for improving both cell-based and cell-free therapy for neurodegenerative diseases.

Show MeSH

Related in: MedlinePlus

Pairwise multiple comparison analyses between groups of NPCs at different time intervals. Pairwise multiple comparison analysis was carried out using Tukey’s HSD (Tukey’s honest significant difference test). The data in red represents mean ± SD for statistically significant results (p < 0.05). P-values stated in blue indicate statistically insignificant comparisons (p > 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4117972&req=5

Fig5: Pairwise multiple comparison analyses between groups of NPCs at different time intervals. Pairwise multiple comparison analysis was carried out using Tukey’s HSD (Tukey’s honest significant difference test). The data in red represents mean ± SD for statistically significant results (p < 0.05). P-values stated in blue indicate statistically insignificant comparisons (p > 0.05).

Mentions: To elucidate the effects of growth factors on proliferation of NPCs we investigated the growth of cells using MTS assays at different time intervals (24 hr, 48 hr, 72 hr, 96 hr, and 120 hr) during the differentiation. Our results showed that the treatment group with IGF-1 had a significantly enhanced proliferation of NPCs at each time interval (Figure 4). To validate these data, we performed a one-way ANOVA across the groups. This demonstrated that IGF-1 could maintain cell proliferation at all time points (n = 12, p < 0.05). Our results were consistent with the previous study by Supeno et al. [16], which found that IGF-1 enhanced the proliferation of neural stem cells. We also carried out multiple comparisons between the groups (Figure 5). These comparisons clearly showed the effects of other growth factors in maintaining cell proliferation and their significance in differentiation activity. However, IGF-1 enhanced proliferation in NPCs more than the other growth factors.Figure 4


IGF-1 enhances cell proliferation and survival during early differentiation of mesenchymal stem cells to neural progenitor-like cells.

Huat TJ, Khan AA, Pati S, Mustafa Z, Abdullah JM, Jaafar H - BMC Neurosci (2014)

Pairwise multiple comparison analyses between groups of NPCs at different time intervals. Pairwise multiple comparison analysis was carried out using Tukey’s HSD (Tukey’s honest significant difference test). The data in red represents mean ± SD for statistically significant results (p < 0.05). P-values stated in blue indicate statistically insignificant comparisons (p > 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4117972&req=5

Fig5: Pairwise multiple comparison analyses between groups of NPCs at different time intervals. Pairwise multiple comparison analysis was carried out using Tukey’s HSD (Tukey’s honest significant difference test). The data in red represents mean ± SD for statistically significant results (p < 0.05). P-values stated in blue indicate statistically insignificant comparisons (p > 0.05).
Mentions: To elucidate the effects of growth factors on proliferation of NPCs we investigated the growth of cells using MTS assays at different time intervals (24 hr, 48 hr, 72 hr, 96 hr, and 120 hr) during the differentiation. Our results showed that the treatment group with IGF-1 had a significantly enhanced proliferation of NPCs at each time interval (Figure 4). To validate these data, we performed a one-way ANOVA across the groups. This demonstrated that IGF-1 could maintain cell proliferation at all time points (n = 12, p < 0.05). Our results were consistent with the previous study by Supeno et al. [16], which found that IGF-1 enhanced the proliferation of neural stem cells. We also carried out multiple comparisons between the groups (Figure 5). These comparisons clearly showed the effects of other growth factors in maintaining cell proliferation and their significance in differentiation activity. However, IGF-1 enhanced proliferation in NPCs more than the other growth factors.Figure 4

Bottom Line: To unravel the roles and effects of different growth factors in the differentiation of MSCs into neural lineages, we have differentiated MSCs into neural lineages using different combinations of growth factors.The NPCs derived from IGF-1 treatment also resulted in a better yield after the terminal differentiation into neurons and glial cells than that of the other treated groups.Our results suggested that IGF-1 has a crucial role in the differentiation of MSCs into neuronal lineage by enhancing the proliferation and reducing the apoptosis in the NPCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Jalan Hospital Universiti Sains Malaysia, 16150 Kubang Kerian, Kota Bharu, Kelantan, Malaysia. teejonghuat@gmail.com.

ABSTRACT

Background: There has been increasing interest recently in the plasticity of mesenchymal stem cells (MSCs) and their potential to differentiate into neural lineages. To unravel the roles and effects of different growth factors in the differentiation of MSCs into neural lineages, we have differentiated MSCs into neural lineages using different combinations of growth factors. Based on previous studies of the roles of insulin-like growth factor 1 (IGF-1) in neural stem cell isolation in the laboratory, we hypothesized that IGF-1 can enhance proliferation and reduce apoptosis in neural progenitor-like cells (NPCs) during differentiation of MSCs into NCPs.We induced MSCs differentiation under four different combinations of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, (C) EGF + bFGF + LIF, (D) EGF + bFGF + BDNF, and (E) without growth factors, as a negative control. The neurospheres formed were characterized by immunofluorescence staining against nestin, and the expression was measured by flow cytometry. Cell proliferation and apoptosis were also studied by MTS and Annexin V assay, respectively, at three different time intervals (24 hr, 3 days, and 5 days). The neurospheres formed in the four groups were then terminally differentiated into neuron and glial cells.

Results: The four derived NPCs showed a significantly higher expression of nestin than was shown by the negative control. Among the groups treated with growth factors, NPCs treated with IGF-1 showed the highest expression of nestin. Furthermore, NPCs derived using IGF-1 exhibited the highest cell proliferation and cell survival among the treated groups. The NPCs derived from IGF-1 treatment also resulted in a better yield after the terminal differentiation into neurons and glial cells than that of the other treated groups.

Conclusions: Our results suggested that IGF-1 has a crucial role in the differentiation of MSCs into neuronal lineage by enhancing the proliferation and reducing the apoptosis in the NPCs. This information will be beneficial in the long run for improving both cell-based and cell-free therapy for neurodegenerative diseases.

Show MeSH
Related in: MedlinePlus