1.The mechanism of human neural stem cell secretomes improves neuropathic pain and locomotor function in spinal cord injury rat models: through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities
I Nyoman SEMITA ; Dwikora Novembri UTOMO ; Heri SUROTO ; I Ketut SUDIANA ; Parama GANDI
The Korean Journal of Pain 2023;36(1):72-83
Background:
Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%–69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)-secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.
Methods:
A proper experimental study investigated 15 Rattus norvegicus divided into normal, control, and treatment groups (30 µL HNSC-secretome, intrathecal in the level of T10, three days post-traumatic SCI). Twentyeight days post-injury, specimens were collected, and matrix metalloproteinase (MMP)-9, F2-Isoprostanes, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and brain derived neurotrophic factor (BDNF) were analyzed. Locomotor recovery was evaluated via Basso, Beattie, and Bresnahan scores. Neuropathic pain was evaluated using the Rat Grimace Scale.
Results:
The HNSC-secretome could improve locomotor recovery and neuropathic pain, decrease F2-Isoprostane (antioxidant), decrease MMP-9 and TNF-α (anti-inflammatory), as well as modulate TGF-β and BDNF (neurotrophic factor). Moreover, HNSC-secretomes maintain the extracellular matrix of SCI by reducing the matrix degradation effect of MMP-9 and increasing the collagen formation effect of TGF-β as a resistor of glial scar formation.
Conclusions
The present study demonstrated the mechanism of HNSC-secretome in improving neuropathic pain and locomotor function in SCI through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.
2.The Role of Human Neural Stem Cell Secretomes on the Repair of Spinal Cord Injury Post-laminectomy in Rattus norvegicus Through the Analysis of Basso–Beattie–Bresnahan Score Locomotors, Interleukin-10, Matrix Metalloproteinase 9, and Transforming Growth Factor-β
I Nyoman SEMITA ; Dwikora Novembri UTOMO ; Heri SUROTO ; I Ketut SUDIANA
Asian Spine Journal 2023;17(2):231-239
Methods:
This experimental study investigated 15 Rattus norvegicus rats that were divided into three groups: (1) normal, (2) SCI+nonsecretome, and (3) SCI+secretome (30 μL, intrathecal Th10). Model subacute SCI post-laminectomy was performed in 60 seconds using an aneurysm Yasargil clip with a closing forceps weighing 65 g (150 kdyn). At 35 days post-injury, the specimens were collected, and the immunohistochemicals of IL-10, MMP9, and TGF-β were analyzed. Motor recovery was evaluated based on the BBB scores.
Results:
The SCI post-laminectomy of rats treated with HNSC secretomes showed improvements in their locomotor recovery based on the BBB scores (p =0.000, mean=18.4) and decreased MMP9 (p =0.015) but had increased the levels of IL-10 (p =0.045) and TGF-β (p =0.01).
Conclusions
These results indicate that the factors associated with the HNSC secretomes can mitigate their pathophysiological processes of secondary damage after SCI and improve the locomotor functional outcomes in rats.