23 research outputs found
The Unexplored Role of Intra-articular Adipose Tissue in the Homeostasis and Pathology of Articular Joints
No full textIntra-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
The Unexplored Role of Intra-articular Adipose Tissue in the Homeostasis and Pathology of Articular Joints
No full textMitochondria and pluripotency: from established models to emerging roles in adult stem cells
No full textPluripotency, once considered an exclusive attribute of early embryonic cells, is increasingly recognized in certain adult tissue-derived stem cell populations, challenging traditional developmental paradigms. Recent findings highlight mitochondria as key regulators of cellular identity, integrating metabolic status, redox signaling, and epigenetic cues to influence stemness and differentiation. This review synthesizes current knowledge on mitochondrial features (from morphology, dynamics, to bioenergetics and correlation to cellular epigenetic status) in pluripotent stem cells (ESCs and iPSCs) as well as in multipotent adult tissue stem cells (ASC) emphasizing transitions between glycolytic and oxidative metabolism during reprogramming and lineage specification. Particular attention is given to existing evidence on adult pluripotent-like stem cells, including VSELs, MAPCs, MUSE cells, MIAMI, and DFATs, which remain incompletely characterized but demonstrate promising regenerative capacities. While direct data on mitochondrial behavior in these cells are sparse, parallels with multipotent adult stem cells as well as with ESC and IPSCs suggest a model wherein stress-induced bioenergetic shifts, ROS signaling, and mitochondrial remodeling act as modulators of latent pluripotency. Understanding these mechanisms could offer insights on adult pluripotent stem cell role in orchestrating regeneration during major trauma or environmental stress as well as on their distinctive responsiveness compared to ASC. Such an approach could inform future strategies in regenerative medicine, offering novel insights into how adult cells might resume developmental plasticity through mitochondrial balance, intercellular transfer and networking
Obesity, Osteoarthritis, and Myokines: Balancing Weight Management Strategies, Myokine Regulation, and Muscle Health
No full textObesity and osteoarthritis (OA) are increasingly prevalent conditions that are intricately linked, with each exacerbating the other’s pathogenesis and worsening patient outcomes. This review explores the dual impact of obesity on OA, highlighting the role of excessive weight in aggravating joint degeneration and the limitations OA imposes on physical activity, which further perpetuates obesity. The role of muscle tissue, particularly the release of myokines during physical activity, is examined in the context of OA and obesity. Myokines such as irisin, IL-6, and myostatin are discussed for their roles in metabolic regulation, inflammation, and tissue repair, offering insights into their potential therapeutic targets. This review emphasizes the importance of supervised weight management methods in parallel with muscle rehabilitation in improving joint health and metabolic balance. The potential for myokine modulation through targeted exercise and weight loss interventions to mitigate the adverse effects of obesity and OA is also discussed, suggesting avenues for future research and therapy development to reduce the burden of these chronic conditions
Towards Regenerative Audiology: Immune Modulation of Adipose-Derived Mesenchymal Cells Preconditioned with Citric Acid-Coated Antioxidant-Functionalized Magnetic Nanoparticles
No full textIntroduction 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
Systems Biology and Stem Cell Pluripotency:Revisiting the Discovery of Induced Pluripotent Stem Cell
No full textRecent breakthroughs in stem cell biology have accelerated research in the area of regenerative medicine. Over the past years, it has become possible to derive patient-specific stem cells which can be used to generate different cell populations for potential cell therapy. Systems biological modeling of stem cell pluripotency and differentiation have largely been based on prior knowledge of signaling pathways, gene regulatory networks, and epigenetic factors. However, there is a great need to extend the complexity of the modeling and to integrate different types of data, which would further improve systems biology and its uses in the field. In this chapter, we first give a general background on stem cell biology and regenerative medicine. Stem cell potency is introduced together with the hierarchy of stem cells ranging from pluripotent embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to tissue-specific multipotent and unipotent stem cells. Secondly, we address some of the systems biological approaches which have already added valuable knowledge to the stem cell field. Particular attention is paid to the most commonly used knowledge-based models as well as to the unsupervised data-driven model. Finally, we will revisit the discovery of the iPSCs by Yamanaka in 2006 and superimpose a data-driven systems biological approach on the data which this amazing discovery was based on. This approach helps to demonstrate how systems biology can complement the field of stem cell biology
