Understanding host-graft crosstalk for predicting the outcome of stem cell transplantation.

Mesenchymal stromal cells (MSCs) hold great promise for tissue regeneration in debilitating disorders. Despite reported improvements, the short-term outcomes of MSC transplantation, which is possibly linked to poor cell survival, demand extensive investigation. Disease-associated stress microenvironments further complicate outcomes. This debate underscores the need for a deeper understanding of the phenotypes of transplanted MSCs and their environment-induced fluctuations. Additionally, questions arise about how to predict, track, and comprehend cell fate post-transplantation. In vivo cellular imaging has emerged as a critical requirement for both short- and long-term safety and efficacy studies. However, translating preclinical imaging methods to clinical settings remains challenging. The fate and function of transplanted cells within the host environment present intricate challenges, including MSC engraftment, variability, and inconsistencies between preclinical and clinical data. The study explored the impact of high glucose concentrations on MSC survival in diabetic environments, emphasizing mitochondrial factors. Preserving these factors may enhance MSC survival, suggesting potential strategies involving genetic modification, biomaterials, and nanoparticles. Understanding stressors in diabetic patients is crucial for predicting the effects of MSC-based therapies. These multifaceted challenges call for a holistic approach involving the incorporation of large-scale data, computational disease modeling, and possibly artificial intelligence to enable deterministic insights.

Stem Cell-Based Therapies for Auditory Hair Cell Regeneration in the Treatment of Hearing Loss.

The incidence and prevalence of hearing loss is increasing globally at an accelerated pace. Hair cells represent the sensory receptors of auditory and vestibular systems. Hair cell absence, loss or degeneration due to congenital diseases, trauma, toxicity, infection or advancing age, results in disabling hearing loss. Regenerative medicine approaches consisting in stem cell-based hair cell rescue or regeneration, gene therapy, as well as cell and tissue engineering are expected to dramatically improve the therapeutic arsenal available for addressing hearing loss. Current strategies that are using different stem cell types to rescue or to induce hair cell proliferation and regeneration are presented. Gene and cell therapy methods that modulates transdifferentiation of surrounding cell types into hair cells are presented, together with their specific advantages and limitations. Several modalities for improving therapeutic targeting to the inner ear such as nanoparticle-mediated cell and gene delivery are introduced. Further steps in building more relevant high-throughput models for testing novel drugs and advanced therapies are proposed as a modality to accelerate translation to clinical settings.

Fe-Cr-Nb-B Magnetic Particles and Adipose-Derived Mesenchymal Cells Trigger Cancer Cell Apoptosis by Magneto-Mechanical Actuation.

Magnetic nanoparticles (MPs) are emerging as powerful and versatile tools for biotechnology, including cancer research and theranostic applications. Stem cell-mediated magnetic particle delivery has been previously recognized as a modality to target sites of malignancies. Here, we propose the use of adipose-derived mesenchymal cells (ADSC) for the targeted delivery of Fe-Cr-Nb-B magnetic particles to human osteosarcoma (HOS) cells and magneto-mechanical actuation (MMA) for targeting and destroying HOS cells. We show that MPs are easily incorporated by ADSCs and HOS cells, as confirmed by TEM images and a ferrozine assay. MP-loaded ADSCs display increased motility towards tumor cells compared with their unloaded counterparts. MMA of MP-loaded ADSCs induces HOS destruction, as confirmed by the MTT and live/dead assays. MMA enables the release of the MPs towards cancer cells, producing a significant decrease (about 80%) in HOS viability immediately after application. In contrast, normal human dermal fibroblasts' (NHDFs) viability exposed to similar conditions remains high, showing a differential behavior of normal and malignant cells to MP load and MMA exposure. Taken together, the method could derive successful strategies for in vivo applications in targeting and destroying malignant cells while protecting normal cells.

Magnetic Nanoparticle Coating Decreases the Senescence and Increases the Targeting Potential of Fibroblasts and Adipose-Derived Mesenchymal Stem Cells.

Magnetic nanoparticles (MNPs) are intensely scrutinized for applications in emerging biomedical fields. Their potential use for drug delivery, tracking, and targeting agents or for cell handling is tested for regenerative medicine and tissue engineering applications. The large majority of MNPs tested for biomedical use are coated with different lipids and natural or synthetic polymers in order to decrease their degradation process and to increase the ability to transport drugs or bioactive molecules. Our previous studies highlighted the fact that the as-prepared MNP-loaded cells can display increased resistance to culture-induced senescence as well as ability to target pathological tissues; however, this effect tends to be dependent on the cell type. Here, we assessed comparatively the effect of two types of commonly used lipid coatings, oleic acid (OA) and palmitic acid (PA), on normal human dermal fibroblasts and adipose-derived mesenchymal cells with culture-induced senescence and cell motility in vitro. OA and PA coatings improved MNPs stability and dispersibility. We found good viability for cells loaded with all types of MNPs; however, a significant increase was obtained with the as-prepared MNPs and OA-MNPs. The coating decreases iron uptake in both cell types. Fibroblasts (Fb) integrate MNPs at a slower rate compared to adipose-derived mesenchymal stem cells (ADSCs). The as-prepared MNPs induced a significant decrease in beta-galactosidase (B-Gal) activity with a nonsignificant one observed for OA-MNPs and PA-MNPs in ADSCs and Fb. The as-prepared MNPs significantly decrease senescence-associated B-Gal enzymatic activity in ADSCs but not in Fb. Remarkably, a significant increase in cell mobility could be detected in ADSCs loaded with OA-MNPscompared to controls. The OA-MNPs uptake significantly increases ADSCs mobility in a wound healing model in vitro compared to nonloaded counterparts, while these observations need to be validated in vivo. The present findings provide evidence that support applications of OA-MNPs in wound healing and cell therapy involving reparative processes as well as organ and tissue targeting.

Towards Regenerative Audiology: Immune Modulation of Adipose-Derived Mesenchymal Cells Preconditioned with Citric Acid-Coated Antioxidant-Functionalized Magnetic Nanoparticles.

Introduction and Background: Based on stem cells, bioactive molecules and supportive structures, regenerative medicine (RM) is promising for its potential impact on field of hearing loss by offering innovative solutions for hair cell rescue. Nanotechnology has recently been regarded as a powerful tool for accelerating the efficiency of RM therapeutic solutions. Adipose-derived mesenchymal cells (ADSCs) have already been tested in clinical trials for their regenerative and immunomodulatory potential in various medical fields; however, the advancement to bedside treatment has proven to be tedious. Innovative solutions are expected to circumvent regulatory and manufacturing issues related to living cell-based therapies. The objectives of the study were to test if human primary ADSCs preconditioned with magnetic nanoparticles coated with citric acid and functionalized with antioxidant protocatechuic acid (MNP-CA-PCA) retain their phenotypic features and if conditioned media elicit immune responses in vitro. MNP-CA-PCA was synthesized and characterized regarding size, colloidal stability as well as antioxidant release profile. Human primary ADSCs preconditioned with MNP-CA-PCA were tested for viability, surface marker expression and mesenchymal lineage differentiation potential. Conditioned media (CM) from ADSCs treated with MNP-CA-PCA were tested for Il-6 and IL-8 cytokine release using ELISA and inhibition of lectin-stimulated peripheral blood monocyte proliferation. Results: MNP-CA-PCA-preconditioned ADSCs display good viability and retain their specific mesenchymal stem cell phenotype. CM from ADSCs conditioned with MNP-CA-PCA do not display increased inflammatory cytokine release and do not induce proliferation of allergen-stimulated allogeneic peripheral blood monocytes in vitro. Conclusions: While further in vitro and in vivo tests are needed to validate these findings, the present results indicated that CM from ADSCs preconditioned with MNP-CA-PCA could be developed as possible cell-free therapies for rescuing auditory hair cells.

Magnetic nanowires substrate increases adipose-derived mesenchymal cells osteogenesis.

Magnetic nanomaterials are increasingly impacting the field of biology and medicine. Their versatility in terms of shape, structure, composition, coating, and magnetic responsivity make them attractive for drug delivery, cell targeting and imaging. Adipose derived-mesenchymal cells (ASCs) are intensely scrutinized for tissue engineering and regenerative medicine. However, differentiation into musculoskeletal lineages can be challenging. In this paper, we show that uncoated nickel nanowires (Ni NW) partially released from their alumina membrane offer a mechanically-responsive substrate with regular topography that can be used for the delivery of magneto-mechanical stimulation. We have used a tailored protocol for improving ASCs adherence to the substrate, and showed that cells retain their characteristic fibroblastic appearance, cytoskeletal fiber distribution and good viability. We report here for the first time significant increase in osteogenic but not adipogenic differentiation of ASCs on Ni NW exposed to 4 mT magnetic field compared to non-exposed. Moreover, magnetic actuation is shown to induce ASCs osteogenesis but not adipogenesis in the absence of external biochemical cues. While these findings need to be verified in vivo, the use of Ni NW substrate for inducing osteogenesis in the absence of specific differentiation factors is attractive for bone engineering. Implant coating with similar surfaces for orthopedic and dentistry could be as well envisaged as a modality to improve osteointegration.

Adipose tissue in bone regeneration - stem cell source and beyond.

Adipose tissue (AT) is recognized as a complex organ involved in major home-ostatic body functions, such as food intake, energy balance, immunomodulation, development and growth, and functioning of the reproductive organs. The role of AT in tissue and organ homeostasis, repair and regeneration is increasingly recognized. Different AT compartments (white AT, brown AT and bone marrow AT) and their interrelation with bone metabolism will be presented. AT-derived stem cell populations - adipose-derived mesenchymal stem cells and pluripotent-like stem cells. Multilineage differentiating stress-enduring and dedifferentiated fat cells can be obtained in relatively high quantities compared to other sources. Their role in different strategies of bone and fracture healing tissue engineering and cell therapy will be described. The current use of AT- or AT-derived stem cell populations for fracture healing and bone regenerative strategies will be presented, as well as major challenges in furthering bone regenerative strategies to clinical settings.

A Simple Protocol for Sample Preparation for Scanning Electron Microscopic Imaging Allows Quick Screening of Nanomaterials Adhering to Cell Surface.

Preparing biological specimens for scanning electron microscopy (SEM) can be difficult to implement, as it requires specialized equipment and materials as well as the training of dedicated personnel. Moreover, the procedure often results in damage to the samples to be analyzed. This work presents a protocol for the preparation of biological samples to evaluate the adherence of nanomaterials on the cell surface using SEM. To this end, we used silicon wafers as a substrate to grow cells and replaced difficult steps such as the critical point drying of the samples in order to make the method quicker and easier to perform. The new protocol was tested using two different types of cells, i.e., human osteosarcoma cells and adipose-derived mesenchymal stem cells, and it proved that it can grossly preserve cell integrity in order to be used to estimate nanomaterials' interaction with cell surfaces.

Magnetic Nanoparticles and Magnetic Field Exposure Enhances Chondrogenesis of Human Adipose Derived Mesenchymal Stem Cells But Not of Wharton Jelly Mesenchymal Stem Cells.

Purpose: Iron oxide based magnetic nanoparticles (MNP) are versatile tools in biology and medicine. Adipose derived mesenchymal stem cells (ADSC) and Wharton Jelly mesenchymal stem cells (WJMSC) are currently tested in different strategies for regenerative regenerative medicine (RM) purposes. Their superiority compared to other mesenchymal stem cell consists in larger availability, and superior proliferative and differentiation potential. Magnetic field (MF) exposure of MNP-loaded ADSC has been proposed as a method to deliver mechanical stimulation for increasing conversion to musculoskeletal lineages. In this study, we investigated comparatively chondrogenic conversion of ADSC-MNP and WJMSC with or without MF exposure in order to identify the most appropriate cell source and differentiation protocol for future cartilage engineering strategies. Methods: Human primary ADSC and WJMSC from various donors were loaded with proprietary uncoated MNP. The in vitro effect on proliferation and cellular senescence (beta galactosidase assay) in long term culture was assessed. In vitro chondrogenic differentiation in pellet culture system, with or without MF exposure, was assessed using pellet histology (Safranin O staining) as well as quantitative evaluation of glycosaminoglycan (GAG) deposition per cell. Results: ADSC-MNP complexes displayed superior proliferative capability and decreased senescence after long term (28 days) culture in vitro compared to non-loaded ADSC and to WJMSC-MNP. Significant increase in chondrogenesis conversion in terms of GAG/cell ratio could be observed in ADSC-MNP. MF exposure increased glycosaminoglycan deposition in MNP-loaded ADSC, but not in WJMSC. Conclusion: ADSC-MNP display decreased cellular senescence and superior chondrogenic capability in vitro compared to non-loaded cells as well as to WJMSC-MNP. MF exposure further increases ADSC-MNP chondrogenesis in ADSC, but not in WJMSC. Loading ADSC with MNP can derive a successful procedure for obtaining improved chondrogenesis in ADSC. Further in vivo studies are needed to confirm the utility of ADSC-MNP complexes for cartilage engineering.

Magnetic nanoparticle loaded human adipose derived mesenchymal cells spheroids in levitated culture.

Magnetic nanoparticles (MNP) are intensely scrutinized for biomedical applications due to their excellent biocompatibility and adjustable magnetic field (MF) responsiveness. Three-dimensional spheroid culture of ADSC improves stem cell proliferation and differentiation, increasing their potential for clinical applications. In this study we aimed to detect if MF levitated culture of ADSC loaded with proprietary MNP maintain the properties of ADSC and improve their performances. Levitated ADSC-MNP formed aggregates with increased volume and reduced number compared to nonlevitated ones. ADSC-MNP from levitated spheroid displayed higher viability, proliferation and mobility compared to nonlevitated and 2D culture. Levitated and nonlevitated ADSC-MNP spheroids underwent three lineage differentiation, demonstrating preserved ADSC stemness. Quantitative osteogenesis showed similar values in MNP-loaded levitated and nonlevitated spheroids. Significant increases in adipogenic conversion was observed for all 3D formulation. Chondrogenic conversion in levitated and nonlevitated spheroids produced comparable ratio glucosaminoglycan (GAG)/DNA. Increased chondrogenesis could be observed for ADSC-MNP in both levitated and nonlevitated condition. Taken together, ADSC-MNP levitated spheroids retain stemness and display superior cell viability and migratory capabilities. Furthermore, the method consistently increases spheroid maneuverability, potentially facilitating large scale manufacturing and automation. Levitated spheroid culture of ADSC-MNP can be further tested for various application in regenerative medicine and organ modeling.

Flash-cooling assisted sol-gel self-ignited synthesis of magnetic carbon dots-based heterostructure with antitumor properties.

This work addresses current direction of the nanoparticles-based systems intended for cancer therapy by developing a newly-formulated innovative chemically-engineered anti-tumor composite consisting in a magnetic, fluorescent, lipophilic, and biologically-active carbon heterostructure capable by itself or through coupling with a chemotherapeutic agent to selectively induce tumor cell death. The anti-tumor compound was synthesized through a modified sol-gel method by addition of a low-cost molecule with recently proven anti-tumor properties which was combusted and flash-cooled along with magnetic iron oxides precursors at 250 °C. The synthesized compound consisted in carbon dots, graphene and hematite nanoparticles which endowed the composite with unique simultaneous fluorescence, magnetic and anti-tumor properties. The in-vitro cytotoxicity performed on tumor cells (human osteosarcoma) and normal cells (fibroblasts) showed a selective cytotoxic effect induced after 24 h of treatment by the drug-free composite, leading to a cell death of 37%, for a composite concentration of 0.01 mg/mL per 104 tumor cells, whereas the composite loaded with an antitumor drug (mitoxantrone) boosted the cell death effect to 47% for similar exposure conditions. The method shows high potential as it boosts drug transfer within tumor cells. Different antitumor drugs already in clinical use can be used following their separate or in-cocktail controlled combustion.

The effect of magnetic field exposure on differentiation of magnetite nanoparticle-loaded adipose-derived stem cells.

Magnetic nanoparticles (MNPs) are versatile tools for various applications in biotechnology and nanomedicine. MNPs-mediated cell tracking, targeting and imaging are increasingly studied for regenerative medicine applications in cell therapy and tissue engineering. Mechanical stimulation influences mesenchymal stem cell differentiation. Here we show that MNPs-mediated magneto-mechanical stimulation of human primary adipose derived stem cells (ADSCs) exposed to variable magnetic field (MF) influences their adipogenic and osteogenic differentiation. ADSCs loaded with biocompatible magnetite nanoparticles of 6.6 nm, and with an average load of 21 picograms iron/cell were exposed to variable low intensity (0.5 mT - LMF) and higher intensity magnetic fields (14.7 and 21.6 mT - HMF). Type, duration, intensity and frequency of MF differently affect differentiation. Short time (2 days) intermittent exposure to LMF increases adipogenesis while longer (7 days) intermittent as well as continuous exposure favors osteogenesis. HMF (21.6 mT) short time intermittent exposure favors osteogenesis. Different exposure protocols can be used to increase differentiation dependently on expected results. Magnetic remotely-actuated MNPs up-taken by ADSCs promotes the shift towards osteoblastic lineage. ADSCs-MNPs under MF exposure could be used for enabling osteoblastic conversion during cell therapy for systemic osteoporosis. Current results enable further in vivo studies investigating the role of remotely-controlled magnetically actuated ADSCs-MNPs for the treatment of osteoporosis.

Association of intracellular lipid accumulation in subcutaneous adipocyte precursors and plasma adipokines in bariatric surgery candidates.

BACKGROUND: The adipocyte expansion is a critical process with implications in the pathogenesis of obesity associated metabolic syndrome. Impaired adipogenesis leads to dysfunctional, hypertrophic adipocytes, local inflammation and peripheric insulin resistance. METHODS: We assessed the relationship between the adipogenic differentiation capacity of the subcutaneous adipose derived stem cells (ASCs), evaluated by total lipid accumulation, and the metabolic and hormonal profile in a group of obese female patients proposed for bariatric surgery (N = 20) versus normal weight female controls (N = 7). RESULTS: The lipid accumulation (measured as optical density at 492 nm) of ASCs during their differentiation to adipocytes was significantly lower in ASCs isolated from obese patients as compared to ASCs isolated from normal weight patients (0.49 ± 0.1 vs. 0.71 ± 0.1, p < 0.001). Significant negative correlations between lipid accumulation in adipogenic differentiated ASCs and plasma concentrations of triglycerides (p < 0.01), insulin (p < 0.001), HOMA-IR (p < 0.01), adiponectin (p < 0.05) and leptin/adiponectin ratio (p < 0.05) were found in obese group. CONCLUSIONS: In severely obese female patients, the abnormal adipogenesis is related to insulin resistance and leptin/adiponectin ratio. The abnormal lipid accumulation in the mature adipocyte derived from obese ASCs could possible predict the further development of type 2 diabetes mellitus in severely obese patients and influence the selection of patients for bariatric surgery.

Human adult pluripotency: Facts and questions.

Cellular reprogramming and induced pluripotent stem cell (IPSC) technology demonstrated the plasticity of adult cell fate, opening a new era of cellular modelling and introducing a versatile therapeutic tool for regenerative medicine. While IPSCs are already involved in clinical trials for various regenerative purposes, critical questions concerning their medium- and long-term genetic and epigenetic stability still need to be answered. Pluripotent stem cells have been described in the last decades in various mammalian and human tissues (such as bone marrow, blood and adipose tissue). We briefly describe the characteristics of human-derived adult stem cells displaying in vitro and/or in vivo pluripotency while highlighting that the common denominators of their isolation or occurrence within tissue are represented by extreme cellular stress. Spontaneous cellular reprogramming as a survival mechanism favoured by senescence and cellular scarcity could represent an adaptative mechanism. Reprogrammed cells could initiate tissue regeneration or tumour formation dependent on the microenvironment characteristics. Systems biology approaches and lineage tracing within living tissues can be used to clarify the origin of adult pluripotent stem cells and their significance for regeneration and disease.

Human adipose-derived stem cells loaded with drug-coated magnetic nanoparticles for in-vitro tumor cells targeting.

Magnetic nanoparticles (MNPs) functionalized with different therapeutics delivered by mesenchymal stem cells represent a promising approach to improve the typical drug delivery methods. This innovative method, based on the "Trojan horse" principle, faces however important challenges related to the viability of the MNPs-loaded cells and drug stability. In the present study we report about an in vitro model of adipose-derived stem cells (ADSCs) loaded with palmitate-coated MNPs (MNPsPA) as antitumor drug carriers targeting a 3D tissue-like osteosarcoma cells. Cell viability, MNPsPA-drug loading capacity, cell speed, drug release rate, magnetization and zeta potential were determined and analysed. The results revealed that ADSCs loaded with MNPsPA-drug complexes retained their viability at relatively high drug concentrations (up to 1.22 pg antitumor drug/cell for 100% cell viability) and displayed higher speed compared to the targeted tumor cells in vitro. The magnetization of the sterilized MNPsPA complexes was 67 emu/g within a magnetic field corresponding to induction values of clinical MRI devices. ADSCs payload was around 9 pg magnetic material/cell, with an uptake rate of 6.25 fg magnetic material/min/cell. The presented model is a proof-of-concept platform for stem cells-mediated MNPs-drug delivery to solid tumors that could be further correlated with MRI tracking and magnetic hyperthermia for theranostic applications.

Comparative effects of magnetic and water-based hyperthermia treatments on human osteosarcoma cells.

INTRODUCTION: Hyperthermia (HT) based on magnetic nanoparticles (MNPs) represents a promising approach to induce the apoptosis/necrosis of tumor cells through the heat generated by MNPs submitted to alternating magnetic fields. However, the effects of temperature distribution on the cancer cells' viability as well as heat resistance of various tumor cell types warrant further investigation. METHODS: In this work, the effects induced by magnetic hyperthermia (MHT) and conventional water-based hyperthermia (WHT) on the viability of human osteosarcoma cells at different temperatures (37°C-47°C) was comparatively investigated. Fe-Cr-Nb-B magnetic nanoparticles were submitted either to alternating magnetic fields or to infrared radiation generated by a water-heated incubator. RESULTS: In terms of cell viability, significant differences could be observed after applying the two HT treatment methods. At about equal equilibrium temperatures, MHT was on average 16% more efficient in inducing cytotoxicity effects compared to WHT, as assessed by MTT cytotoxicity assay. CONCLUSION: We propose the phenomena can be explained by the significantly higher cytotoxic effects initiated during MHT treatment in the vicinity of the heat-generating MNPs compared to the effects triggered by the homogeneously distributed temperature during WHT. These in vitro results confirm other previous findings regarding the superior efficiency of MHT over WHT and explain the cytotoxicity differences observed between the two antitumor HT methods.

Stem cells as delivery vehicles for regenerative medicine-challenges and perspectives.

The use of stem cells as carriers for therapeutic agents is an appealing modality for targeting tissues or organs of interest. Combined delivery of cells together with various information molecules as therapeutic agents has the potential to enhance, modulate or even initiate local or systemic repair processes, increasing stem cell efficiency for regenerative medicine applications. Stem-cell-mediated delivery of genes, proteins or small molecules takes advantage of the innate capability of stem cells to migrate and home to injury sites. As the native migratory properties are affected by in vitro expansion, the existent methods for enhancing stem cell targeting capabilities (modified culture methods, genetic modification, cell surface engineering) are described. The role of various nanoparticles in equipping stem cells with therapeutic small molecules is revised together with their class-specific advantages and shortcomings. Modalities to circumvent common challenges when designing a stem-cell-mediated targeted delivery system are described as well as future prospects in using this approach for regenerative medicine applications.

The Unexplored Role of Intra-articular Adipose Tissue in the Homeostasis and Pathology of Articular Joints.

Intra-articular adipose tissue deposits known as articular fat pads (AFPs) are described to exist within synovial joints. Their assumed role in normal joint biomechanics is increasingly objectivized by means of advanced methods of functional imaging. AFPs possess structural similarity with body subcutaneous white adipose tissue (WAT), however, seems to be regulated by independent metabolic loops. AFP dimension are conserved during extreme WAT states: obesity, metabolic syndrome, lipodystrophy, and cachexia. Hoffa fat pad (HFP) in the knee is increasingly recognized as a major player in pathological joint states such as anterior knee pain and osteoarthritis. HFP contains numerous population of mesenchymal and endothelial progenitors; however, the possible role of mature adipocytes in the maintenance of stem cell niche is unknown. We propose that AFP is an active component of the joint organ with multifunctional roles in the maintenance of joint homeostasis. Endowed with a rich network of sensitive nervous fibbers, AFPs may act as a proprioceptive organ. Adipokines and growth factors released by AFP-resident mature adipocytes could participate in the maintenance of progenitor stem cell niche as well as in local immune regulation. AFP metabolism may be locally controlled, correlated with but independent of WAT homeostasis. The identification of AFP role in normal joint turnover and its possible implication in pathological states could deliver diagnostic and therapeutic targets. Drug and/or cell therapies that restore AFP structure and function could become the next step in the design of disease modifying therapies for disabling joint conditions such as osteoarthritis and inflammatory arthritis.

Human Adipose Derived Stem Cells and Osteoblasts Interaction with Fe-Cr-Nb-B Magnetic Nanoparticles.

The use of materials at nanoscale is currently of increasing interest for life sciences and medicine. Magnetic nanoparticles (MNPs) are under scrutiny for a large array of applications in nanomedicine as diagnostic and therapeutic tools. Proprietary Fe-Cr-Nb-B MNPs display heating properties that recommends them as potent agents for delivery of local hyperthermia for the treatment of solid tumours. Stem cell mediated delivery represents a safe and accurate modality to target remote or metastatic tumour sites. In this study we investigated the interaction of Fe-Cr-Nb-B nanoparticles with human adipose derived mesenchymal stem cells and human primary osteoblasts. We found that: (a) bare and chitosan coated Fe-Cr-Nb-B are internalized by both cell types, (b) they can be detected up to 28 days inside the cells without signs of membrane disruption and (c) they do not display in vitro toxicity. MNPs are uploaded by cells in a time dependent manner with maximum uptake after 7-8 days cell-particle incubation. Particle internalization do not interfere with proliferative and differentiation potential (osteogenesis and adipogenesis) demonstrating an unaltered cellular phenotype. Further investigation of the potential effect of MNPs internalization on cytoskeleton dynamics and in inducing oxidative stress will be required as it is of interest for predicting cell migration and survival after transplantation. Present results are encouraging for designing a stemcell mediated delivery of Fe-Cr-Nb-B magnetic nanoparticles to solid tumour sites for hyperthermia applications.

Stem cells for the treatment of musculoskeletal pain.

Musculoskeletal-related pain is one of the most disabling health conditions affecting more than one third of the adult population worldwide. Pain from various mechanisms and origins is currently underdiagnosed and undertreated. The complexity of molecular mechanisms correlating pain and the progression of musculoskeletal diseases is not yet fully understood. Molecular biomarkers for objective evaluation and treatment follow-up are needed as a step towards targeted treatment of pain as a symptom or as a disease. Stem cell therapy is already under investigation for the treatment of different types of musculoskeletal-related pain. Mesenchymal stem cell-based therapies are already being tested in various clinical trials that use musculoskeletal system-related pain as the primary or secondary endpoint. Genetically engineered stem cells, as well as induced pluripotent stem cells, offer promising novel perspectives for pain treatment. It is possible that a more focused approach and reassessment of therapeutic goals will contribute to the overall efficacy, as well as to the clinical acceptance of regenerative medicine therapies. This article briefly describes the principal types of musculoskeletal-related pain and reviews the stem cell-based therapies that have been specifically designed for its treatment.