Effects Of Bone Marrow Mononuclear Cells Research Articles

Different mechanisms guide the antinociceptive effect of bone marrow-mononuclear cells and bone marrow-mesenchymal stem/stromal cells in trigeminal neuralgia

AimsTrigeminal neuralgia (TN) is a type of chronic orofacial pain evoked by trivial stimuli that manifests as episodes of excruciating and sudden, recurrent paroxysmal pain. Most patients are refractory to pharmacological therapy used for the treatment of TN. Mononuclear cells (MNC) and mesenchymal stem/stromal cells (MSC) have shown therapeutic potential in painful neuropathies, but their mechanism of action is not fully understood. The present work aimed to investigate the antinociceptive effect and mechanism of action of MNC and MSC in experimental TN. Materials and methodsMice submitted to the chronic constriction injury of the infraorbital nerve (CCI-ION) mouse model of TN received a single intravenous injection of saline, MNC, or MSC (1 × 106 cells/mouse). The effect of the treatments on the behavioral signs of painful neuropathy, morphological aspects of the infraorbital nerve, and inflammatory and oxidative stress markers in the infraorbital nerve were assessed. Key findingsMNC and MSC improved behavioral painful neuropathy, activated key cell signaling antioxidant pathways by increasing Nrf2 expression, and reduced the proinflammatory cytokines IL-1β and TNF-α. However, treatment with MSC, but not MNC, was associated with a sustained increase of IL-10 and with the re-establishment of the morphometric pattern of the infraorbital nerve, indicating a difference in the mechanism of action between MNC and MSC. In line with this result, in IL-10 knockout mice, MSC transplantation did not induce an antinociceptive effect. SignificanceImportantly, these data suggest an IL-10-induced disease-modifying profile related to MSC treatment and reinforce cell therapy's potential in treating trigeminal neuralgia.

Bone-marrow mononuclear cells and acellular human amniotic membrane improve global cardiac function without inhibition of the NLRP3 Inflammasome in a rat model of heart failure.

Recent studies have suggested that therapies with stem cells and amniotic membrane can modulate the inflammation following an ischemic injury in the heart. This study evaluated the effects of bone-marrow mononuclear cells (BMMC) and acellular human amniotic membrane (AHAM) on cardiac function and NLRP3 complex in a rat model of heart failure.On the 30th day,the echocardiographic showed improvements on ejection fraction and decreased pathological ventricular remodeling on BMMC and AHAM groups.Oxidative stress analysis was similar between the three groups,and the NLRP3 inflammasome activity were not decreased with the therapeutic use of both BMMC and AHAM,in comparison to the control group.

Rat Bone Marrow-Derived Mononuclear Cells Outperform Folic Acid in the Treatment of Diabetic Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats

Background: Diabetes mellitus is the most common cause of peripheral neuropathy, which itself is mediated in part via oxidative stress. Recent studies have used stem-cell-based therapies to regenerate nerve tissues following diabetic neuropathy. Folic acid supplementation promotes neuronal development and protection in some neurological diseases. Aim: This study aims to compare the effects of bone marrow-mononuclear cells (BM-MNCs) and folic acid (FA) in the treatment of peripheral neuropathy in streptozotocin-induced diabetic rats. Methods: Forty adult male albino rats were randomly divided into five groups: Group I (healthy control group); Group II, diabetic group (a single intraperitoneal streptozotocin injection); Group III, diabetic rats that received BM-MNCs; Group IV, diabetic rats that were treated with FA (10 mg/kg/day intraperitoneal injection) for 4 weeks and Group V (FA): Folic Acid-treated group. Random blood sugar was measured for all groups. The animals were euthanized, and the right sciatic nerve was carefully extracted to measure sciatic nerve conduction velocity and processed for histopathological, immunohistochemical (CD68), electron microscopic and morphometric studies. Results: The diabetic group showed progressive histological changes characteristic of neuropathy in the sciatic nerve. Also increased number of CD68-immunopositive cells were detected. In BM-MNC transplantation group, the sciatic nerve sections showed improved histological changes characteristic of neuropathy with a decreased number of CD68-immunopositive cells. The diabetic group treated with FA showed less histological results relative to diabetic rats treated with BM-MNCs. Conclusion: Diabetic rats treated with BM-MNC showed better improvement in diabetic neuropathy than diabetic rats treated with folic acid.

Comparison of Bone Marrow-derived Mononuclear Cells vs. Mesenchymal Stem Cells in Protecting Random-pattern Skin Flap Survival in Rats

Both cultured Bone Marrow Mesenchymal Stem Cells (BMSCs) and non-cultured Bone Marrow Mononuclear Cells (BM-MNCs) can improve random-pattern skin flap survival. However, whether prior culture expansion of bone marrow cells is beneficial for this therapy remains unclear. In the current study, the protective effects of BM-MNCs and BMSCs derived from identical bone marrow aspirates were compared in a random-pattern skin flap rat model. The mean skin flap survival rates were 71.6 ± 8.4% in the BM-MNC-treated group and 66.2 ± 3.1% in the BMSCtreated group, both of which were significantly higher than the control group (55.9 ± 3.4%). The protective effects were confirmed by blood perfusion analysis and vessel density assay. However, no significant difference was observed between the cell transplanted groups. These results indicate that the current method for pre-culture of BMSCs does not bring therapeutic benefits in skin flap protection. Therefore, BM-MNCs without pre-culture might be more practicable in the clinical setting.

Uncultured bone marrow mononuclear cells delay the dedifferentiation of unexpanded chondrocytes in pellet culture

Uncultured bone marrow mononuclear cells (BMMC) were recently used to successfully repair damaged cartilage. However, the effect of BMMCs on the proliferation and differentiation of chondrocytes that are critical to cartilage repair is unclear. Here, we investigate the influence of BMMCs on chondrocyte dedifferentiation in pellet culture. We isolated and mixed BMMCs and chondrocytes in a 1:1 (BMMC/C) ratio and cultured in pellets (1.6 × 10(6) cells per pellet) for 2, 4, or 8weeks. Chondrocyte differentiation was evaluated using macrography, histological examination, immunohistochemistry and gene expression analysis. While a transparent and smooth surface was observed in both BMMC/C and chondrocyte cultures over time, the former was smaller in size after 2 and 4weeks of culture. Interestingly, after 8weeks, BMMC/C cultures became significantly larger than chondrocyte cultures (P = 0.003). The distribution of a cartilage-specific extracellular matrix (ECM), that includes components like glycosaminoglycan (GAG) and type II collagen, was gradually reduced in chondrocyte cultures. On the other hand, while we found no obvious differences in the ECM in BMMC/C cultures between 2 and 4weeks in vitro, after 8weeks the concentration of ECM components decreased significantly. Further, we detected an upregulation of cartilage-specific genes in BMMC/C cultures, when compared with chondrocytes. Altogether, we demonstrate that co-culture with BMMCs delays the dedifferentiation of chondrocytes in pellet cultures in vitro. This suggests that uncultured BMMC, which can be quickly and safely obtained, could serve as a potential alternative cell source for engineering of cartilage tissue.

Potential advantages of cell administration on the inflammatory response compared to standard ACE inhibitor treatment in experimental myocardial infarction

BackgroundBone Marrow (BM) progenitor cells can target the site of myocardial injury, contributing to tissue repair by neovascolarization and/or by a possible direct paracrine effect on the inflammatory cascade. Angiotensin Converting Enzyme inhibitors (ACE-I) are effective in reducing mortality and preventing left ventricular (LV) function deterioration after myocardial infarction.MethodsWe investigated the short term effects of BM mononuclear cells (BMMNCs) therapy on the pro-inflammatory cytokines (pro-CKs) and on LV remodelling and compared these effects over a standard ACE-I therapy in a rat model of myocardial cryodamage.Forty two adult inbread Fisher-F344 rats were randomized into three groups: untreated (UT; n = 12), pharmacological therapy (ACE-I; n = 14, receiving quinapril), and cellular therapy (BMMNCs; n = 16, receiving BMMNCs infusion). Rats underwent to a standard echocardiogram in the acute setting and 14 days after the damage, before the sacrifice. Pro-CKs analysis (interleukin (IL)1β, IL-6, tumor necrosis factor (TNF)α was performed (multiplex proteome arrays) on blood samples obtained by direct aorta puncture before the sacrifice; a control group of 6 rats was considered as reference.ResultsConcerning the extension of the infarcted area as well as the LV dimensions, no differences were observed among the animal groups; treated rats had lower left atrial diameters and higher indexes of LV function. Pro-Cks were increased in infarcted-UT rats if compared with controls, and significantly reduced by BMMNCs and ACE-I ; TNFα inversely correlated with LV fractional shortening.ConclusionAfter myocardial infarction, both BMMNCs and ACE-I reduce the pattern of pro-Ck response, probably contributing to prevent the deterioration of LV function observed in UT rats.