Paracrine-Mediated Neuroprotection and Neuritogenesis of Axotomised Retinal Ganglion Cells by Human Dental Pulp Stem Cells: Comparison with Human Bone Marrow and Adipose-Derived Mesenchymal Stem Cells

Abstract

We have investigated and compared the neurotrophic activity of human dental pulp stem cells (hDPSC), human bone marrow-derived mesenchymal stem cells (hBMSC) and human adipose-derived stem cells (hAMSC) on axotomised adult rat retinal ganglion cells (RGC) in vitro in order to evaluate their therapeutic potential for neurodegenerative conditions of RGC. Using the transwell system, RGC survival and length/number of neurites were quantified in coculture with stem cells in the presence or absence of specific Fc-receptor inhibitors to determine the role of NGF, BDNF, NT-3, VEGF, GDNF, PDGF-AA and PDGF-AB/BB in stem cell-mediated RGC neuroprotection and neuritogenesis. Conditioned media, collected from cultured hDPSC/hBMSC/hAMSC, were assayed for the secreted growth factors detailed above using ELISA. PCR array determined the hDPSC, hBMSC and hAMSC expression of genes encoding 84 growth factors and receptors. The results demonstrated that hDPSC promoted significantly more neuroprotection and neuritogenesis of axotomised RGC than either hBMSC or hAMSC, an effect that was neutralized after the addition of specific Fc-receptor inhibitors. hDPSC secreted greater levels of various growth factors including NGF, BDNF and VEGF compared with hBMSC/hAMSC. The PCR array confirmed these findings and identified VGF as a novel potentially therapeutic hDPSC-derived neurotrophic factor (NTF) with significant RGC neuroprotective properties after coculture with axotomised RGC. In conclusion, hDPSC promoted significant multi-factorial paracrine-mediated RGC survival and neurite outgrowth and may be considered a potent and advantageous cell therapy for retinal nerve repair.

Immunomodulatory and neuroprotective effect of cryopreserved allogeneic mesenchymal stem cells on spinal cord injury in rats

“…These results support the hypothesis that MSCs can act in secondary events favoring neuronal survival and regeneration (Nakamura et al, 2003;Yune et al, 2003;Mead et al, 2014).…”

“…Similarly, the reduced TGF-β expression observed at 21 days in the GMSC may also have decreased formation of the glial scar and stimulated the recovery of motor function in the present study. As observed in previous studies (Hawryluk et al, 2012;Mead et al, 2014), MSCs cannot produce or stimulate the synthesis of BDNF. However, some authors reported increased expression of BDNF in animals subjected to injury and treated with MSCs (Osaka et al, 2010;Zhou et al, 2013;Kingham et al, 2014).…”

“…MSCs modify their secretion profile according to their microenvironment. In addition, there is variability in the production capacity of neurotrophins among MSCs from different individuals and tissues (Zhukareva et al, 2010;Mead et al, 2014).…”

Revisiting the role of erythropoietin for treatment of ocular disorders

“…107 Various stem cells such as embryonic stem cells, [108][109][110] hematopoietic stem cells, [111][112][113] mesenchymal stem cells (MSCs), [114][115][116] induced pluripotent stem cells, 117,118 and EPC 119,120 have been shown to demonstrate the capability to regenerate into retinal neurons, 108,[110][111][112][113]117 retinal pigmented epithelium, 109,121,122 and improve blood vessels permeability 123 in both in vitro and in vivo studies. It is noteworthy that the transplanted cells will need to survive the harsh microenvironment before cell programming can occur for the replacement of damaged tissue.…”

The transplantation of mesenchymal stem cells derived from unconventional sources: an innovative approach to multiple sclerosis therapy

“…Indeed, secretome of DT-MSCs contains elevated levels of BDNF, neurotrophin-3, GDNF, and NGF (Mead, Logan et al 2014). In addition, compared to BM-MSCs and AD-MSCs secretome, DT-MSCs secreted important growth factors and cytokines such as VEGF, RANTES, FLT-3, MCP-1, Fractalkine, and GM-CSF (Ahmed et al 2016).…”