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Secretome Cues Modulate the Neurogenic Potential of Bone Marrow and Dental Stem Cells

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Abstract

Dental tissue is emerging as a promising source of stem cells especially in nerve regeneration mainly due to their neural origin and ease of harvest. We isolated dental stem cells from three sources, namely, dental pulp (DPSCs), dental follicle (DFSCs), and apical papilla (SCAP), and explored the efficacy of each towards neural differentiation in comparison to bone marrow-derived stem cells. The neural differentiation potential was assessed by expression of various neural markers and neurosphere assay. We observed that DPSCs were inherently predisposed towards neural lineage. To further delineate the paracrine cues responsible for the differences in neural differentiation potential, we harvested the conditioned secretome from each of the stem cell population and observed their effect on colony formation, neurite extension, and neural gene expression of IMR-32, a pre-neuroblastic cell line. We found that neural differentiation was significantly enhanced when IMR-32 cells were treated with secretome derived from DMSCs as compared to the same from BMSCs. Th1/Th2/Th17 cytokine array revealed DPSC secretome had higher expression of the cytokines like GCSF, IFNγ, and TGFβ that promote neural differentiation. Thus, we concluded that DPSCs may be the preferred source of cells for obtaining neural lineage among the four sources of stem cells. Our results also indicate that the DPSC-secreted factors may be responsible for their propensity towards neural differentiation. This study suggests that DPSCs and their secretomes can be a potentially lucrative source for cell-based and “cell-free” (secretome) therapy for neural disorders and injury.

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Acknowledgments

AK received fellowship support from CSIR, Govt. of India.

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Authors and Affiliations

  1. Department of Biophysics, PGIMER, Chandigarh, 160012, India

    Ajay Kumar & Shalmoli Bhattacharyya

  2. Department of Nephrology, PGIMER, Chandigarh, India

    Vinod Kumar & Vivekanand Jha

  3. Unit of Oral and Maxillofacial surgery, Oral health science centre, PGIMER, Chandigarh, India

    Vidya Rattan

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Correspondence to Shalmoli Bhattacharyya.

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Electronic supplementary material

Figure S1

FACS characterization and multilineage differentiation of primary stem cells. a. FACS cytogram of BMSCs, b. DPSC, c. SCAP, d. DFSC to show the expression level of different stem cell markers, for DPSC (n = 5), SCAP (n = 5) and DFSC (n = 5) and BMSC (n = 3), e. Multilineage potential of different stem cell populations in cellular derivatives of osteocytes (alizarin red staining), adipocytes (oil red O staining is visible in lipid droplets) and hepatocytes (final images are merged images of LDL Dylight fluorochrome-red for low density lipoprotein uptake and LDL receptor-green). Magnification is 10X for osteocytes and 20X for adipocytes and hepatocytes, scale bar 100 μm (GIF 17 kb)

High resolution image (TIFF 2217 kb)

Figure S2

Intensity surface plots representing a 3D reconstruction of antibody binding intensities of NFM and MAP-2 antibody expression on surface of neural cells obtained after neural differentiation (GIF 7 kb)

High resolution image (TIFF 548 kb)

Figure S3

Neurosphere integrity assay. DIC images of neurospheres generated from different stem cells post seven days of differentiation and after 24 h of maintenance on adherent cell culture plate. Magnification-20X, scale bar 100 μm (GIF 5 kb)

High resolution image (TIFF 1020 kb)

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Kumar, A., Kumar, V., Rattan, V. et al. Secretome Cues Modulate the Neurogenic Potential of Bone Marrow and Dental Stem Cells. Mol Neurobiol 54, 4672–4682 (2017). https://doi.org/10.1007/s12035-016-0011-3

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  • DOI: https://doi.org/10.1007/s12035-016-0011-3

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