Bone marrow‐derived mesenchymal stem cells alleviate paclitaxel‐induced mechanical allodynia in rats

Abstract

Anticancer drug paclitaxel (PTX) frequently causes painful peripheral neuropathy; however, no medication has been shown to be effective in the treatment of this debilitating side effect. We aimed to investigate the efficacy of two different doses of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) on PTX-induced mechanical allodynia and spinal cytokine levels and their localization to target tissues such as the spinal cord and sciatic nerve. After the development of mechanical allodynia with repeated PTX administration, two different doses of rat BM-MSCs, low or high (1 × 10 6 -5 × 10 6 ), were transplanted into rats and the evaluation continued for 30 days. Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-10 levels in spinal cord samples of animals were analyzed by enzyme-linked immunosorbent assay. PTX-induced mechanical allodynia was relieved significantly 15 days after the transplantation of high-dose of BM-MSCs. Both MSCs doses were effective in alleviating allodynia, but the onset of effect was earlier with the high dose. High-dose of BM-MSCs significantly decreased spinal IL-1β and TNF-α levels compared to the PTX group. Fluorescent dye-labeled BM-MSCs were observed much more frequently in the sciatic nerve and spinal cord samples of the high-dose BM-MSCs transplanted group than in the low-dose group animals. In conclusion, we found that the antiallodynic effects of BM-MSCs appeared earlier when high-dose of cells were administered. We think that other mechanisms may play a role in the effects of MSCs, besides localization to damaged tissues and reducing spinal inflammatory cytokine levels. We show that BM-MSCs can be a novel approach in PTX-induced mechanical allodynia.

Effects of Physical Cues on Stem Cell-Derived Extracellular Vesicles toward Neuropathy Applications

“…Xiang et al also observed the secretion of anti-inflammatory and anti-fibrotic factors that effectively improved renal function and inhibited the harmful progression of DPN [ 216 ]. Within CIPN, the administration of MSCs reversed the pain in mice exposed to chemotherapeutic medications known to negatively affect mitochondrial function and increase oxidative stress [ 220 , 221 ]. After 24 days of MSC treatment, mitochondrial respiration was restored, attributed to the increased MSC and M2 macrophage expression of IL-10 signaling [ 221 ].…”

“…After 24 days of MSC treatment, mitochondrial respiration was restored, attributed to the increased MSC and M2 macrophage expression of IL-10 signaling [ 221 ]. The limitations of the systemic administration of MSCs are still an issue, requiring an abundant amount of MSCs in the hope that they stay viable, successfully differentiate, and accurately treat the desired target site [ 220 , 224 ].…”

“…BM-MSC CIPN Bone marrow-derived mesenchymal stem cells alleviate paclitaxel-induced mechanical allodynia in rats. [220] MSC CIPN Nasal administration of mesenchymal stem cells reverses chemotherapy-induced peripheral neuropathy in mice.…”

Multipotent Mesenchymal Stem Cell-Based Therapies for Spinal Cord Injury: Current Progress and Future Prospects

“…For instance, inflammatory cytokines, such as TNF-α and IL-1β, have been reported to influence MSC differentiation, potentially biasing MSCs towards a particular cell phenotype, such as astrocytes. High levels of these pro-inflammatory cytokines have been shown to inhibit neuronal differentiation while promoting the differentiation of MSCs into astrocytes [40,41]. On the other hand, anti-inflammatory cytokines, such as IL-4 and IL-10, have been reported to promote neuronal differentiation and inhibit glial differentiation of MSCs [42].…”

Intravenous application of human umbilical cord mesenchymal stem cells alleviate neuropathic pain by suppressing microglia activation in rats

“…To date, intravenous injection remains the most commonly used, convenient, and easily applicable method in clinical practice. However, the therapeutic effect of MSCs via intravenous injection might be affected by the potentially depositing in lung [ 18 , 19 ], yet the limited evidence upon peripheral neuropathic pain treatment was inconsistent [ 20 , 21 ]. Therefore, further investigations are imperative to clarify the efficacy and the concomitant underlying mechanisms of MSC administration via intravenous intervention.…”