Insulin-like growth factor-1 short-period therapy stimulates bone marrow cells in obese swiss mice.

Bone marrow cells (BMCs) from obese Swiss mice fed with Western diet show mitochondrial dysfunction. Obesity interferes with BMCs disrupting energetic metabolism, stimulating apoptosis, and reducing cell proliferation since adipose tissue releases inflammatory adipokines into the medullar microenvironment. These changes lead to reduction of BMC differentiation capacity and hematopoiesis impairment, a process responsible for blood cell continuous production through hematopoietic stem cells (HSCs). This work aimed to analyze the effects of IGF-1 therapy on BMC viability in Western diet-induced obesity, in vivo. We observed that after only 1 week of treatment, obese Swiss mice presented reduced body weight and visceral fat and increased mitochondrial oxidative capacity and coupling, indicating mitochondrial function improvement. In addition, IGF-1 was able to reduce apoptosis of total BMCs, stem cell subpopulations (hematopoietic and mesenchymal), and leukocytes, restoring all progenitor hematopoietic lineages. The treatment also contributed to increase proliferative capacity of hematopoietic stem cells and leukocytes, keeping the hematopoietic and immune systems balanced. Therefore, we conclude that IGF-1 short period therapy improved BMC survival, proliferation, and differentiation capacity in obese Swiss mice.

Tomographic and histomorphometric evaluation of socket healing after tooth extraction using leukocyte- and platelet-rich fibrin: A randomized, single-blind, controlled clinical trial.

The use of platelet concentrate in alveolar ridge preservation has been broadly studied. However, no randomized clinical trials with histomorphometric analysis and low risk of bias are available in the literature. We conducted a prospective, single-blind, parallel, randomized, controlled clinical trial to evaluate the efficacy of leukocyte- and platelet-rich fibrin (L-PRF) in socket preservation after tooth extraction. Additionally, the effect of L-PRF on bone formation was analyzed histologically using bone biopsy specimens obtained during implant placement. A total of 48 subjects who underwent a non-molar tooth extraction were randomly assigned to the L-PRF group (n = 24) or the control group (n = 24). Cone-beam computed tomographies were performed immediately after tooth extraction and at 3 months after tooth extraction, prior to implant surgery. A significant difference in bone resorption was registered 1 mm below the crest: 0.93 ± 0.9 mm for the L-PRF group and 2.27 ± 1.2 mm for the control group (p = 0.0001). Histomorphometric analysis showed a higher percentage of new bone formation in the L-PRF group compared with the control group. The values were 55.96 ± 11.97% and 39.69 ± 11.13%, respectively (p = 0.00001). These findings indicate that the administration of L-PRF should always be considered when socket preservation is planned (Clinicaltrials.gov NCT03408418).

Impaired mitochondrial function and reduced viability in bone marrow cells of obese mice.

Bone marrow cells (BMCs) are the main type of cells used for transplantation therapies. Obesity, a major world health problem, has been demonstrated to affect various tissues, including bone marrow. This could compromise the success of such therapies. One of the main mechanisms underlying the pathogenesis of obesity is mitochondrial dysfunction, and recent data have suggested an important role for mitochondrial metabolism in the regulation of stem cell proliferation and differentiation. Since the potential use of BMCs for clinical therapies depends on their viability and capacity to proliferate and/or differentiate properly, the analysis of mitochondrial function and cell viability could be important approaches for evaluating BMC quality in the context of obesity. We therefore compared BMCs from a control group (CG) and an obese group (OG) of mice and evaluated their mitochondrial function, proliferation capacity, apoptosis, and levels of proteins involved in energy metabolism. BMCs from OG had increased apoptosis and decreased proliferation rates compared with CG. Mitochondrial respiratory capacity, biogenesis, and the coupling between oxidative phosphorylation and ATP synthesis were significantly decreased in OG compared with CG, in correlation with increased levels of uncoupling protein 2 and reduced peroxisome proliferator-activated receptor-coactivator 1α content. OG also had decreased amounts of the glucose transporter GLUT-1 and insulin receptor (IRß). Thus, Western-diet-induced obesity leads to mitochondrial dysfunction and reduced proliferative capacity in BMCs, changes that, in turn, might compromise the success of therapies utilizing these cells.