Adipose Tissue-Derived Mesenchymal Stromal Cells from Ex-Morbidly Obese Individuals Instruct Macrophages towards a M2-Like Profile .

Obesity, which continues to increase worldwide, was shown to irreversibly impair the differentiation potential and angiogenic properties of adipose tissue mesenchymal stromal cells (ADSCs). Because these cells are intended for regenerative medicine, especially for the treatment of inflammatory conditions, and the effects of obesity on the immunomodulatory properties of ADSCs are not yet clear, here we investigated how ADSCs isolated from former obese subjects (Ex-Ob) would influence macrophage differentiation and polarization, since these cells are the main instructors of inflammatory responses. Analysis of the subcutaneous adipose tissue (SAT) of overweight (OW) and Ex-Ob subjects showed the maintenance of approximately twice as many macrophages in Ex-Ob SAT, contained within the CD68/FXIII-A inflammatory pool.

The role of macrophages in fracture healing: a narrative review of the recent updates and therapeutic perspectives.

Objective: This review addresses the latest advances in research on the role of macrophages in fracture healing, exploring their relationship with failures in bone consolidation and the perspectives for the development of advanced and innovative therapies to promote bone regeneration.

Background: The bone can fully restore its form and function after a fracture. However, the regenerative process of fracture healing is complex and is influenced by several factors, including macrophage activity.

The Effects of Titanium Dioxide Nanoparticles on Osteoblasts Mineralization: A Comparison between 2D and 3D Cell Culture Models.

Although several studies assess the biological effects of micro and titanium dioxide nanoparticles (TiO NPs), the literature shows controversial results regarding their effect on bone cell behavior. Studies on the effects of nanoparticles on mammalian cells on two-dimensional (2D) cell cultures display several disadvantages, such as changes in cell morphology, function, and metabolism and fewer cell-cell contacts. This highlights the need to explore the effects of TiO NPs in more complex 3D environments, to better mimic the bone microenvironment.

Establishing a Diaphyseal Femur Fracture Model in Mice.

Bones have a significant regenerative capacity. However, fracture healing is a complex process, and depending on the severity of the lesions and the age and overall health status of the patient, failures can occur, leading to delayed union or nonunion. Due to the increasing number of fractures resulting from high-energy trauma and aging, the development of innovative therapeutic strategies to improve bone repair based on the combination of skeletal/mesenchymal stem/stromal cells and biomimetic biomaterials is urgently needed.

The Isolation and Manufacture of GMP-Grade Bone Marrow Stromal Cells from Bone Specimens.

Bone marrow stromal cells (BMSCs, also known as bone marrow mesenchymal stem cells) are a plastic-adherent heterogeneous cell population that contain inherent skeletal progenitors and a subset of multipotential skeletal stem cells (SSCs). Application of BMSCs in therapeutic protocols implies its isolation and expansion under good manufacturing practices (GMP). Here we describe the procedures we have found to successfully generate practical BMSCs numbers, with preserved biological potency.

The Manufacture of GMP-Grade Bone Marrow Stromal Cells with Validated In Vivo Bone-Forming Potential in an Orthopedic Clinical Center in Brazil.

In vitro-expanded bone marrow stromal cells (BMSCs) have long been proposed for the treatment of complex bone-related injuries because of their inherent potential to differentiate into multiple skeletal cell types, modulate inflammatory responses, and support angiogenesis. Although a wide variety of methods have been used to expand BMSCs on a large scale by using good manufacturing practice (GMP), little attention has been paid to whether the expansion procedures indeed allow the maintenance of critical cell characteristics and potency, which are crucial for therapeutic effectiveness. Here, we described standard procedures adopted in our facility for the manufacture of clinical-grade BMSC products with a preserved capacity to generate bone in vivo in compliance with the Brazilian regulatory guidelines for cells intended for use in humans.

Atrophic nonunion stromal cells form bone and recreate the bone marrow environment in vivo.

Introduction: Nonunion is a challenging condition in orthopaedics as its etiology is not fully understood. Clinical interventions currently aim to stimulate both the biological and mechanical aspects of the bone healing process by using bone autografts and surgical fixation. However, recent observations showed that atrophic nonunion tissues contain putative osteoprogenitors, raising the hypothesis that its reactivation could be explored to achieve bone repair.

Bone intramedullary reaming grafts the fracture site with CD146 skeletal progenitors and downmodulates the inflammatory environment.

Introduction: Femoral shaft fractures generally occur in young adults following a high-energy trauma and are prone to delayed union/non-union. Novel therapies to stimulate bone regeneration will have to mimic some of the aspects of the biology of fracture healing; however, which are these aspects is unclear. Locked intramedullary nailing is the current treatment of choice for the stabilisation of femur shaft fractures, and it is associated with accelerated healing and increased union rates.

Vertical femoral neck fractures in young adults: a closed fixation strategy using a transverse cancellous lag screw.

Vertical femoral neck fractures (Pauwels type III classification) in young adults generally occur as a consequence of high-energy trauma and are frequently seen in association with multiple injuries. Considering the controversies regarding the optimal fixation for this fracture, our aim was to evaluate the clinical outcome of a closed fixation strategy for vertical femoral neck fractures in young adults using two parallel and one transverse cancellous lag screws. This was a single-surgeon, prospective study including 20 young adults with average age of 38.

PS1/-Secretase-Mediated Cadherin Cleavage Induces -Catenin Nuclear Translocation and Osteogenic Differentiation of Human Bone Marrow Stromal Cells.

Bone marrow stromal cells (BMSCs) are considered a promising tool for bone bioengineering. However, the mechanisms controlling osteoblastic commitment are still unclear. Osteogenic differentiation of BMSCs requires the activation of -catenin signaling, classically known to be regulated by the canonical Wnt pathway.

Mesenchymal stromal cells from bone marrow treated with bovine tendon extract acquire the phenotype of mature tenocytes.

Objective: This study evaluated in vitro differentiation of mesenchymal stromal cells isolated from bone marrow, in tenocytes after treatment with bovine tendon extract.

Methods: Bovine tendons were used for preparation of the extract and were stored at -80 °C. Mesenchymal stromal cells from the bone marrow of three donors were used for cytotoxicity tests by means of MTT and cell differentiation by means of qPCR.

The effect of autologous concentrated bone-marrow grafting on the healing of femoral shaft non-unions after locked intramedullary nailing.

The aim of this study was to assess the union rates in a series of patients with failed femoral shaft aseptic non-union who were treated with percutaneous concentrated autologous bone marrow grafting. Bone marrow harvesting and cell injection were performed under general anaesthesia in a single surgical procedure. Radiographic union was diagnosed in fractures with a score ≥ 10 according to the radiographic union scale in tibial fractures (RUST) and confirmed by clinical examination.

Late adherent human bone marrow stromal cells form bone and restore the hematopoietic microenvironment in vivo.

Bone marrow stromal cells (BMSCs) are a valuable resource for skeletal regenerative medicine because of their osteogenic potential. In spite of the very general term "stem cell," this population of cells is far from homogeneous, and different BMSCs clones have greatly different phenotypic properties and, therefore, potentially different therapeutic potential. Adherence to a culture flask surface is a primary defining characteristic of BMSCs.

Heterologous mesenchymal stem cells successfully treat femoral pseudarthrosis in rats.

Background: This study evaluated the effectiveness of treating pseudarthrosis in rats by using bone marrow cell suspensions or cultures of bone marrow mesenchymal stromal cells

Methods: Thirty-eight specific pathogen-free (SPF) animals were randomly assigned to four groups: Group 1, Control, without surgical intervention; Group 2 (Placebo), experimental model of femoral pseudarthrosis treated only with saline solution; Group 3, experimental model of femoral pseudarthrosis treated with heterologous bone marrow cells suspension; Group 4, experimental model of femoral pseudarthrosis treated with cultures of heterologous mesenchymal stromal cells from bone marrow. When pseudarthrosis was confirmed by simple radiological studies, digital radiography and histopathology after a 120-day postoperative period, Groups 2, 3 and 4 were treated as above. At 30, 60 and 90 days after the treatment, all animals were evaluated by simple radiological studies, and at the end of the experiment, the animals were assessed by computed axial tomography and anatomopathological and histomorphometric examinations.