Live-cell therapy has emerged as a revolutionary treatment modality, providing a novel therapeutic avenue for intractable diseases. However, a major challenge in live-cell therapy is to maintain live-cell viability and efficacy during the treatment. Microcarriers are crucial for enhancing cell retention, viability, and functions by providing a protective scaffold and creating a supportive environment for live-cell proliferation and metabolism. For microcarrier construction, the microfluidic technology demonstrates excellent characteristics in terms of controllability over microcarrier size and morphology as well as potential for high-throughput production. To date, multiple live-cell delivery microcarrier types (e.g., microspheres, microfibers, and microneedles) are prepared via microfluidic liquid templates to meet different therapeutic needs. In this review, recent developments in microfluidics-based microcarriers for live-cell delivery are presented. It is focused on categorizing the structural design of microfluidic-derived cell-laden microcarriers, and summarizing various therapeutic applications. Finally, an outlook is provided on the future challenges and opportunities in this field.

Exercise-conditioned mesenchymal stem cells (MSCs) may modulate immune responses and improve white adipose tissue (WAT) function. While MSCs are known to reduce inflammation, it remains unclear if exercise-stimulated MSCs can improve obesity-related dysfunctions. This study is the first to explore how exercise-conditioned MSCs may influence adipose tissue inflammation and remodeling in the context of obesity. MSCs were isolated from exercised- and sedentary donor mice, then cultured in vitro. After culture, MSCs were assessed for differentiation capacity and cytokine gene expression, including Il10, as indicators of immune modulation. Exercise-conditioned MSCs were then transplanted into obese recipient mice. Following transplantation, immune cell profiles, inflammatory markers, and adipocyte morphology in recipient WAT were analyzed. Flow cytometry was used to quantify macrophage subtypes (pro-inflammatory and anti-inflammatory), and histological analysis was performed to measure changes in adipocyte size. Exercise-activated MSCs showed a ± 35% increase in Il10 expression and a ± 20% enhancement in differentiation capacity compared to controls, indicating improved immunomodulatory potential. In recipient mice, transplantation led to a ± 25% reduction in pro-inflammatory macrophages (CD86+ CD206-) and a 15% decrease in adipocyte size within WAT. Additionally, WAT in treated mice showed balanced inflammatory profiles and reduced adipose hypertrophy, suggesting restored immune balance and metabolic health. These findings suggest that exercise-modified MSCs exhibit enhanced immunomodulatory and metabolic regulatory properties. This study provides evidence that exercise enhances MSC characteristics, potentially improving their capacity to modulate adipose tissue immune balance and metabolic function in obesity. Exercise-conditioned MSCs may serve as a foundation for future strategies that integrate exercise-induced stem cell modifications to modulate obesity-related metabolic dysfunction.

One of the long-standing challenges in the field of tissue repair and regeneration is the rapid establishment of local microvascular circulation and restoration of perfusion at the site of defects or injuries. Recently, adipose tissue-derived microvascular fragments (ad-MVFs) have attracted increasing attention from researchers. Adipose tissue is rich in blood vessels, and significant progress has been made in the extraction and preservation techniques for microvascular fragments within it. Ad-MVFs promote tissue and organ repair and regeneration through three main mechanisms. First, they accelerate rapid and efficient vascularization at the injury site, enabling early vessel perfusion. Second, the stem cell components within ad-MVFs provide a rich source of cells for tissue and organ regeneration. Third, they play a role in immune regulation, facilitating integration with host tissues after implantation. The application methods of ad-MVFs are diverse. They can be directly implanted or pre-cultivated, facilitating their combination with various scaffolds and broadening their application scope. These properties have led to the wide use of ad-MVFs in tissue engineering, with promising prospects. This review demonstrates that ad-MVFs can serve as a reliable and highly feasible unit for tissue regeneration.

Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen type VI α3 (COL6A3). COL6A3 levels were strongly increased by body mass index and increased coronary artery disease risk. Notably, the carboxyl terminus product of COL6A3, endotrophin, drove this effect. COL6A3 was highly expressed in disease-relevant cell types and tissues. Finally, we found that body fat reduction could reduce plasma levels of COL6A3-derived endotrophin, indicating a tractable way to modify endotrophin levels. In summary, we provide actionable insights into how circulating proteins mediate the effects of obesity on cardiometabolic diseases and prioritize endotrophin as a potential therapeutic target.

Prunella vulgaris L.(PV) and Tussilago farfara (TF) are perennial herbs rich in flavonoids and phenolic compounds with immense medicinal value. PV extract (PV-E) possesses potent antipyretic, anti-inflammtory, antioxidant, antiseptic, anti-cancer and immune stimulatory properties and have been traditionally known for the treatment of wounds, ulcers and sores. TF extract (TF-E) has been known for antibacterial, antioxidant, anti-inflammatory, anti-viral, anti-diabetic, anti-cancer, anti-obesity and wound healing effects. Additionally, TF-E infusions have been used for asthma, cough, and bronchopneumonia treatments.

The therapeutic efficacy of transplanted human adipose stem cells (hASCs) is abrogated under the deteriorating effects of heat stress offered by burn wounds. Earlier researches has documented antioxidant priming as an effective strategy to enhance stem cell performance. As both PV-E and TF-E are known for their potent antioxidant effects. The present study aims to examine the cryoprotective effects of PV-E and TF-E priming on hASCs against in-vitro heat-induced thermal stress. Moreover, we determined the anti-inflammatory potential of both PV-E and TF-E on rabbits.

Antioxidant capacity of both PV-E and TF-E is examined via DPPH assay and anti-inflammatory activity is assessed in rabbits using carrageen-induced paw edema model of inflammation. Next, we investigate the efficacy of different doses (1.25-100 μg/ml) of PV-E and TF-E on hASCs; MTT, LDH, calcein AM staining, and wound scratch assay were used to assess cell viability, cytotoxicity, proliferation ability and cell migration potential in the cells. Then, hASCs were pretreated for 24 h with optimum doses of PV-E and TF-E determined from MTT assay results and were subsequently exposed to in-vitro thermal injury (51 °C,10 min). The cytoprotective effects of both PV-E and TF-E priming under thermal stress were investigated via MTT, LDH, annexin-V staining and gene expression analysis.

Both PV-E and TF-E extracts demonstrated potent antioxidant and effective anti-inflammatory activities, with a clear reduction in inflammation. Study on hASCs exhibited improved cell viabilities, enhanced cell proliferation and migration abilities of both extracts. While heat stress data revealed that PV-E (2.5 μg/ml) and TF-E (5 μg/ml) pretreatment significantly ameliorated effects of thermal-injuries in hASCs as depicted by significantly enhanced cell viabilities, low LDH release profile, and lower annexin-V expression and regulated gene expression of the pretreated cells.

PV-E and TF-E priming effectively enabled hASCs to combat thermal injury by significantly promoting cell survival than untreated cells. Hence, these findings suggest that PV-E and TF-E priming could be used to attain improved cellular responses and enhanced therapeutic efficacy in burnt tissue.

Obesity is a critical risk factor for the development of metabolic diseases and is often associated with dysfunctional adipocytes. Prevalent treatments such as lifestyle intervention, pharmacotherapy, and bariatric surgery are often accompanied by adverse side effects and poor patient compliance. Nanotechnology and cell-based therapy offer innovative approaches for targeted obesity treatments, as they can directly target adipocytes, regulate lipid metabolism, and minimize off-target effects. Here, we provide an overview of the intricate relationship between adipocytes and obesity, highlighting the potential of nanotechnology and cell-based therapy in obesity treatment. Additionally, we discuss the advancements of adipose-derived mesenchymal stem cells (ADMSCs) in obesity progression, including the latest challenges and considerations for developing adipose-targeted treatments for obesity. The objective is to provide a perspective on the design and development of nanotechnology and cell-based therapy for treating obesity and related comorbidities.

Obesity is associated with several comorbidities that cause high mortality rates worldwide. Thus, the study of adipose tissue (AT) has become a target of high interest because of its crucial contribution to many metabolic diseases and metabolizing potential. However, many AT-related physiological, pathophysiological, and toxicological mechanisms in humans are still poorly understood, mainly due to the use of non-human animal models. Organ-on-chip (OoC) platform is a promising alternative to animal models. However, the use of adipose-derived human mesenchymal stem cells (hASCs) in these models is still scarce, and more knowledge on the effects properties of culturing hASCs in OoC models is needed. Here, we present the development of an OoC using hASCs to assess adipogenic differentiation. The device capability to increase hASC differentiation levels was confirmed by Nile red staining to verify lipid droplets inside cells after 10 days of culture and fluid flow of 10 µL/h. The Adipo-on-a-chip system increases hASC proliferation and differentiation area compared with the standard culture method under static conditions (96-well plates) verified in hASCs from different donors by image analysis of cells stained with Nile red. The expression of the gene FABP4 is lower in the MPS, which calls attention to different homeostasis and control of lipids in cells in the MPS, compared with the plates. An increase of hASC proliferation in the MPS related to the 96-well plate was verified through protein Ki-67 expression. Cell and nuclei morphology (area, roundness, perimeter, width, length, width to length rate, symmetry, compactness, axial and radial properties to nuclei, and texture) and dominant direction of cells inside the MPS were evaluated to characterize hASCs in the present model. The presented microphysiological system (MPS) provides a promising tool for applications in mechanistic research aiming to investigate adipogenesis in AT and toxicological assessment based on the hASC differentiation potential.

Knee osteoarthritis (OA) is a leading cause of disability, with current treatment options often falling short of providing satisfactory outcomes. Autologous-cultured adipose-derived mesenchymal stem cells (ADMSCs) and stromal vascular fractions (SVFs) have emerged as potential regenerative therapies.

A comprehensive search was conducted among multiple databases for studies up to June 2023. The risk of bias was assessed in randomized and non-randomized studies, adhering to PRISMA guidelines. The study has been registered with PROSPERO (CRD 42023433160).

Our analysis encompassed 31 studies involving 1,406 patients, of which, 19 studies with 958 patients were included in a meta-analysis, examining both SVF and autologous-cultured ADMSC methods. Significant pain reduction was observed with autologous-cultured ADMSCs starting at 3 months (MD = -2.43, 95% CI, -3.99, -0.86), whereas significant pain mitigation in response to SVF therapy was found to start at 12 months (MD = -2.13, 95% CI, -3.06, -1.21). Both autologous-cultured ADMSCs and SVF provided significant improvement in knee function starting at 12 months (MD = -9.19, 95% CI, -12.48, -5.90 vs. MD = -9.09, 95% CI, -12.67, -5.51, respectively). We found no evidence of severe adverse events linked directly to ADMSC therapy.

Autologous-cultured ADMSCs offer a promising alternative for more rapid pain relief in knee OA, with both ADMSCs and SVF demonstrating substantial long-term benefits in joint function and cartilage regeneration, in the absence of any severe ADMSC-related adverse events.

Hepatocellular carcinoma (HCC) is a common cause of cancer-related mortality and morbidity globally, and with the prevalence of metabolic-related diseases, the incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) related hepatocellular carcinoma (MAFLD-HCC) continues to rise with the limited efficacy of conventional treatments, which has created a major challenge for HCC surveillance. Immune checkpoint inhibitors (ICIs) and molecularly targeted drugs offer new hope for advanced MAFLD-HCC, but the evidence for the use of both types of therapy in this type of tumour is still insufficient. Theoretically, the combination of immunotherapy, which awakens the body's anti-tumour immunity, and targeted therapies, which directly block key molecular events driving malignant progression in HCC, is expected to produce synergistic effects. In this review, we will discuss the progress of immunotherapy and molecular targeted therapy in MAFLD-HCC and look forward to the opportunities and challenges of the combination therapy.

Mesenchymal stem cells (MSCs) have demonstrated considerable potential in tissue repair and the treatment of immune-related diseases, but there are problems with homing efficiency during MSCs transplantation. Exercise, as an intervention, has been shown to have an important impact on the properties of MSCs. This review summarizes the effects of exercise on the properties (including proliferation, apoptosis, differentiation, and homing) of bone marrow-derived MSCs and adipose-derived MSCs. Studies indicated that exercise enhances bone marrow-derived MSCs proliferation, osteogenic differentiation, and homing while reducing adipogenic differentiation. For adipose-derived MSCs, exercise enhances proliferation and reduces adipogenic differentiation. In addition, studies have investigated the therapeutic effects of combined therapy of MSCs transplantation with exercise on diseases of the bone, cardiac, and nervous systems. The combined therapy improves tissue repair by increasing the homing of transplanted MSCs and cytokine secretion (such as neurotrophin 4). Furthermore, MSCs transplantation also has potential for the treatment of obesity. Although the effect is not significant in weight loss, MSCs transplantation shows effects in controlling blood glucose, improving dyslipidemia, reducing inflammation, and improving liver disease. Finally, the potential role of combined MSCs transplantation and exercise therapy in addressing obesity is discussed.

Loss-of-function mutations of the gene encoding the trafficking protein particle complex subunit 9 (Trappc9) cause autosomal recessive intellectual disability and obesity by unknown mechanisms. Genome-wide analysis links Trappc9 to nonalcoholic fatty liver disease (NAFLD). Trappc9-deficient mice have been shown to appear overweight shortly after weaning. Here, we analyzed serum biochemistry and histology of adipose and liver tissues to determine the incidence of obesity and NAFLD in Trappc9-deficient mice and combined transcriptomic and proteomic analyses, pharmacological studies, and biochemical and histological examinations of postmortem mouse brains to unveil mechanisms involved. We found that Trappc9-deficient mice presented with systemic glucose homeostatic disturbance, obesity, and NAFLD, which were relieved upon chronic treatment combining dopamine receptor D2 (DRD2) agonist quinpirole and DRD1 antagonist SCH23390. Blood glucose homeostasis in Trappc9-deficient mice was restored upon administering quinpirole alone. RNA-sequencing analysis of DRD2-containing neurons and proteomic study of brain synaptosomes revealed signs of impaired neurotransmitter secretion in Trappc9-deficient mice. Biochemical and histological studies of mouse brains showed that Trappc9-deficient mice synthesized dopamine normally, but their dopamine-secreting neurons had a lower abundance of structures for releasing dopamine in the striatum. Our study suggests that Trappc9 loss of function causes obesity and NAFLD by constraining dopamine synapse formation.

Diabetes mellitus is a highly prevalent disease characterized by hyperglycaemia that damages the vascular system, leading to micro- (retinopathy, neuropathy, nephropathy) and macrovascular diseases (cardiovascular disease). There are also secondary complications of diabetes (cardiomyopathy, erectile dysfunction or diabetic foot ulcers). Stem cell-based therapies have become a promising tool targeting diabetes symptoms and its chronic complications. Among all stem cells, adipose-derived mesenchymal stem cells (ADMSCs) are of great importance because of their abundance, non-invasive isolation and no ethical limitations. Characteristics that make ADMSCs good candidates for cell-based therapy are their wide immunomodulatory properties and paracrine activities through the secretion of an array of growth factors, chemokines, cytokines, angiogenic factors and anti-apoptotic molecules. Besides, after transplantation, ADMSCs show great ex vivo expansion capacity and differentiation to other cell types, including insulin-producing cells, cardiomyocytes, chondrocytes, hepatocyte-like cells, neurons, endothelial cells, photoreceptor-like cells, or astrocytes. Preclinical studies have shown that ADMSC-based therapy effectively improved visual acuity, ameliorated polyneuropathy and foot ulceration, arrested the development and progression of diabetic kidney disease, or alleviated the diabetes-induced cardiomyocyte hypertrophy. However, despite the positive results obtained in animal models, there are still several challenges that need to be overcome before the results of preclinical studies can be translated into clinical applications. To date, there are several clinical trials or ongoing trials using ADMSCs in the treatment of diabetic complications, most of them in the treatment of diabetic foot ulcers. This narrative review summarizes the most recent outcomes on the usage of ADMSCs in the treatment of long-term complications of diabetes in both animal models and clinical trials.

The traditional treatment of diabetic wounds is unsatisfactory. Exosomes isolated from bone marrow mesenchymal stem cells (BMSCs) promote the healing of diabetic wounds. However, whether the exosomes secreted by interferon (IFN)-γ-pretreated BMSCs have an enhanced therapeutic effect on diabetic wound healing and the relevant mechanisms remain unclear.

In this study, we isolated exosomes from the corresponding supernatants of BMSCs with (IExos) or without IFN-γ treatment (NExos). Human umbilical vein endothelial cells (HUVECs) were used to investigate the proliferation, migration, and tube formation under different treatments in vitro. Diabetic mice were induced by intraperitoneal administration of streptozotocin, and a circular full-thickness dermal defect was then made on the back of each mouse, followed by a multisite subcutaneous injection of phosphate buffered saline or exosomes. Hematoxylin-eosin (H&E) staining, Masson's trichrome staining, and histological analysis were performed to assess the speed and quality of wound healing.

NExos treatment accelerated the healing of diabetic wounds by promoting angiogenesis in vivo and in vitro, and IExos exhibited superior therapeutic efficiency. MicroRNA (miR)-126-3p was significantly increased in IExos, and exosomal miR-126-3p promoted angiogenesis and diabetic wound healing via its transfer to HUVECs. miR-126-3p regulates SPRED1 by directly targeting the 3'-UTR. Mechanistically, IFN-γ-pretreated BMSCs secreted miR-126-3p-enriched exosomes, which enhanced the function of HUVECs and promoted angiogenesis via the SPRED1/Ras/Erk pathway.

Exosomal miR-126-3p secreted from IFN-γ-pretreated BMSCs exhibited higher therapeutic efficacy than NExos in diabetic wound healing by promoting angiogenesis via the SPRED1/Ras/Erk axis.

Bioactive polysaccharides are a promising way for bone disease prevention with high efficiency. Schizophyllan (SPG) is a polysaccharide derived from a species of fungus with anticancer, antitumor, and anti-inflammatory effects. In the present study, for the first time, the cell proliferation, osteogenic markers, mineral deposition, and osteogenic gene expression of human adipose tissue-derived mesenchymal stem cells (hADMSCs) grown on SPG were evaluated by in vitro assays.

The cytotoxicity of SPG was measured using the MTT assay and acridine orange staining. Differentiation of hADMSCs was assessed using alkaline phosphatase (ALP) activity test, cellular calcium content assay, and mineralized matrix staining. To this end, Alizarin red S, von Kossa staining, and the expression of bone-specific markers, including ALP, Runx2, and osteonectin, were used by real-time RT-PCR over a 2-week period. According to the results, SPG at 10 µg/ml concentration was determined as the optimal dosage for differentiation studies. The results of osteogenic differentiation tests showed that compared to the control groups in vitro, SPG enhanced the osteogenic markers and mineralization as well as upregulation of the expression of bone specific genes in differentiated hADMSCs during differentiation.

The results revealed that SPG could be applied as effective factor for osteogenic differentiation in the future. The current study provides insights into the hADMSC-based treatment and introduces promising therapeutic material for individuals who suffer from bone defects and injuries.

To investigate whether ADSC-derived miR-23-enriched exosomes could protect against calcium oxalate stone formation in a hyperoxaluria rat model.

An ethylene glycol- (EG-) induced hyperoxaluria rat model and an in vitro model of COM-induced HK-2 cells coculturing with RAW264.7 cells were established to explore the protective mechanisms of ADSC-derived miR-23-enriched exosomes.

The results showed that treatment with miR-23-enriched exosomes from ADSCs protected EG-induced hyperoxaluria rats, and cell experiments confirmed that coculturing with miR-23-enriched exosomes alleviated COM-induced cell autophagy. Overexpressed miR-23 suppressed M1 macrophage polarization by inhibiting IRF1 expression. Furthermore, the predicted binding site between the IRF1 messenger RNA 3'-untranslated region (3'-UTR) and miR-23 was confirmed by the dual-luciferase reporter assay.

In conclusion, our research gave the first evidence that ADSC-derived miR-23-enriched exosomes affected the polarization of M1 macrophages by directly inhibiting IRF1 and protecting against calcium oxalate stone formation in a hyperoxaluria rat model.

The Akt substrate of 160 kDa (AS160), also known as TBC1 domain family member 4 (TBC1D4), represents a crucial regulator of insulin-stimulated glucose uptake in skeletal muscle and adipose tissue. Recent evidence suggests that AS160/TBC1D4 may also control the cellular entry of long-chain fatty acids (LCFAs), resulting in changes to the lipid profile of muscles and fat cells in lean subjects. However, there are virtually no data on AS160/TBC1D4 expression and its modulatory role in lipid metabolism in the adipocytes from morbidly obese individuals of different metabolic status. In this study, we evaluated the effect of the three main factors, i.e., AS160 silencing, obesity, and metabolic syndrome on lipid uptake and profile in fully differentiated adipocytes derived from mesenchymal stem cells (ADMSCs) of lean and obese (with/without metabolic syndrome) postmenopausal women. Additionally, we tested possible interactions between the explanatory variables. In general, obesity translated into a greater content of fatty acid transporters (especially CD36/SR-B2 and SLC27A4/FATP4) and boosted accumulation of all the examined lipid fractions, i.e., triacylglycerols (TAGs), diacylglycerols (DAGs), and free fatty acids (FFAs). The aforementioned were further enhanced by metabolic syndrome. Moreover, AS160 deficiency also increased the abundance of SLC27A4/FATP4 and CD36/SR-B2, especially on the cell surface of the adipocytes derived from ADMSCs of subcutaneous deposit. This was further accompanied by increased LCFA (palmitic acid) uptake. Despite the aforementioned, AS160 silencing seemed unable to significantly affect the phenotype of the adipocytes stemming from obese patients with respect to their cellular lipid profile as we observed virtually no changes in TAG, DAG, and FFA contents when compared to cells with the reference level of proteins. Nevertheless, knockdown of AS160 stimulated fatty acid oxidation, which may indicate that adaptive mechanisms counteract excessive lipid accumulation. At the same time, adipocytes of visceral origin were rather insensitive to the applied intervention.

The worldwide increase in the prevalence of diabetes mellitus has raised the demand for new therapeutic strategies targeting diabetic symptoms and its chronic complications. Among different treatment options for diabetes, adipose-derived mesenchymal stem cells (ADMSCs) therapy attract the most attention. The therapeutic effects of ADMSCs are based primarily on their paracrine release of immunomodulatory, anti-inflammatory, and trophic factors. Animal models of diabetes as well as human clinical trials have shown that ADMSCs can effectively facilitate endogenous β cell regeneration, preserve residual β cell mass, reduce islet graft rejection, regulate the immune system, and ultimately improve insulin sensitivity or ameliorate insulin resistance in peripheral tissues. Nevertheless, transplantation of mesenchymal stem cells is associated with certain risks; therefore recently much attention has been devoted to ADMSCs derivatives, such as exosomes or conditioned media, as therapeutic agents for the treatment of diabetes. Compared to ADMSCs, cell-free therapy has even better therapeutic potential. This narrative review summarizes recent outcomes and molecular mechanisms of ADMSCs action in the treatment for both type 1 DM and type 2 DM, as well as shows their feasibility, benefits, and current limitations.

Over the last decade, adipose-derived stem cells (ADSCs) have attracted increasing attention in the field of regenerative medicine. ADSCs appear to be the most advantageous cell type for regenerative therapies owing to their easy accessibility, multipotency, and active paracrine activity. This review highlights current challenges in translating ADSC-based therapies into clinical settings and discusses novel strategies to overcome the limitations of ADSCs. To further establish ADSC-based therapies as an emerging platform for regenerative medicine, this review also provides an update on the advancements in this field, including fat grafting, wound healing, bone regeneration, skeletal muscle repair, tendon reconstruction, cartilage regeneration, cardiac repair, and nerve regeneration. ADSC-based therapies are expected to be more tissue-specific and increasingly important in regenerative medicine.

Intra-articular injection of mesenchymal stromal cells (MSCs) with immunomodulatory features and their paracrine secretion of regenerative factors proposed a noninvasive therapeutic modality for cartilage regeneration in knee osteoarthritis (KOA).

Total number of 40 patients with KOA enrolled in two groups. Twenty patients received intra-articular injection of 100 × 10⁶ allogeneic adipose-derived mesenchymal stromal cells (AD-MSCs), and 20 patients as control group received placebo (normal saline). Questionnaire-based measurements, certain serum biomarkers, and some cell surface markers were evaluated for 1 year. Magnetic resonance imaging (MRI) before and 1 year after injection was performed to measure possible changes in the articular cartilage.

Forty patients allocated including 4 men (10%) and 36 women (90%) with average age of 56.1 ± 7.2 years in control group and 52.8 ± 7.5 years in AD-MSCs group. Four patients (two patients from AD-MSCs group and two patients from the control group) excluded during the study. Clinical outcome measures showed improvement in AD-MSCs group. Hyaluronic acid and cartilage oligomeric matrix protein levels in blood serum decreased significantly in patients who received AD-MSCs (P < 0.05). Although IL-10 level significantly increased after 1 week (P < 0.05), the serum level of inflammatory markers dramatically decreased after 3 months (P < 0.001). Expressions of CD3, CD4, and CD8 have a decreasing trend during 6-month follow-up (P < 0.05), (P < 0.001), and (P < 0.001), respectively. However, the number of CD25⁺ cells increased remarkably in the treatment group 3 months after intervention (P < 0.005). MRI findings showed a slight increase in the thickness of tibial and femoral articular cartilages in AD-MSCs group. The changes were significant in the medial posterior and medial anterior areas of ​​the tibia with P < 0.01 and P < 0.05, respectively.

Inter-articular injection of AD-MSCs in patients with KOA is safe. Laboratory data, MRI findings, and clinical examination of patients at different time points showed notable articular cartilage regeneration and significant improvement in the treatment group.

Iranian registry of clinical trials (IRCT, https://en.irct.ir/trial/46 ), IRCT20080728001031N23. Registered 24 April 2018.

The rapid increase in both the lifespan and proportion of older adults is accompanied by the unprecedented rise in age-associated chronic diseases, including sarcopenia and obesity. Aging is also manifested by increased susceptibility to multiple endogenous and exogenous stresses enabling such chronic conditions to develop. Among the main physiological regulators of cellular adaption to various stress stimuli, such as DNA damage, hypoxia, and oxidative stress, are sestrins (Sesns), a family of three evolutionarily conserved proteins, Sesn1, 2, and 3. Age-associated sarcopenia and obesity are characterized by two key processes: (i) accumulation of senescent cells in the skeletal muscle and adipose tissue and (ii) creation of a systemic, chronic, low-grade inflammation (SCLGI). Presumably, failed SCLGI resolution governs the development of these chronic conditions. Noteworthy, Sesns activate senolytics, which are agents that selectively eliminate senescent cells, as well as specialized pro-resolving mediators, which are factors that physiologically provide inflammation resolution. Sesns reveal clear beneficial effects in pre-clinical models of sarcopenia and obesity. Based on these observations, we propose a novel treatment strategy for age-associated sarcopenia and obesity, complementary to the conventional therapeutic modalities: Sesn activation, SCLGI resolution, and senescent cell elimination.

Type 2 diabetes mellitus (T2DM) is a lifelong condition and a grave threat to human health. Innovative efforts to relieve its detrimental effects are acutely needed. The sine qua non in T2DM management is consistent adherence to a prudent lifestyle and nutrition, combined with aerobic and resistance exercise regimens, together repeatedly shown to lead to complete reversal and even long-term remission. Non-adherence to the above lifestyle adjustments condemns any treatment effort and ultimately the patient to a grim fate. It is thus imperative that every study evaluating the effects of innovative interventions in T2DM objectively compares the novel treatment modality to lifestyle modifications, preferably through double-blind controlled randomization, before claiming efficacy.

We previously reported that synthetic oleoyl chalcones had a favorable effect to alleviate metabolic consequences of obesity in male SD rats. In this work, we prepared and characterized by spectroscopic tools, a set of six oleoyl chalcones (5a-c, 10 and 11a,b). The comparative effects of the previously prepared oleoyl chalcones and their new synthetic analogs on metabolic and histological changes in obese male SD rats were studied. It was found that the oleoyl chalcones III_a and IV were the best in improving many metabolic parameters, e. g., FBG, FI, ISI, TG, and total cholesterol. They cured systemic inflammation, through inhibition of the TNF-α and induction of adiponectin production. Moreover, chalcones III_a and IV alleviated the oxidative stress accompanying obesity through the induction of the antioxidant enzymes GPX, SOD and CAT besides, GSH. Interestingly, chalcones III_a and IV exerted hepatoprotective potency and ameliorated the manifestations of NAFLD via inhibition of apoptosis and induction of autophagy of hepatic cells. In conclusion, the oleoyl chalcones III_a and IV were the most effective candidates among the series of synthetic chalcones in correcting body weight and the consequent metabolic and histological changes in adiposity.

Mesenchymal stem cells have a known regenerative potential and are used in many indications. They secrete many growth factors, including for fibroblasts (FGF), endothelium (VEGF), as well as 14 anti-inflammatory cytokines, and they stimulate tissue regeneration, promoting the secretion of proteins and glycosaminoglycans of extracellular matrices, such as collagen I, II, III, and V, elastin, and also metalloproteinases. They secrete exosomes that contain proteins, nucleic acids, lipids, and enzymes. In addition, they show the activity of inactivating free radicals. The aim of this study was an attempt to collect the existing literature on the use of stem cells in the treatment of a burn wound. There were 81 studies included in the analysis. The studies differed in terms of the design, burn wound model, source of stem cells, and methods of cellular therapy application. No major side effects were reported, and cellular therapy reduced the healing time of the burn wound. Few case reports on human models did not report any serious adverse events. However, due to the heterogeneity of the evidence, cellular therapy in burn wound treatment remains an experimental method.

Genetic mutations of trappc9 cause intellectual disability with the atrophy of brain structures and variable obesity by poorly understood mechanisms. Trappc9-deficient mice develop phenotypes resembling pathological changes in humans and appear overweight shortly after weaning, and thus are useful for studying the pathogenesis of obesity. Here, we investigated the effects of trappc9 deficiency on the proliferation and differentiation capacity of adipose-derived stem cells (ASCs). We isolated ASCs from mice before overweight was developed and found that trappc9-null ASCs exhibited signs of premature senescence and cell death. While the lineage commitment was retained, trappc9-null ASCs preferred adipogenic differentiation. We observed a profound accumulation of lipid droplets in adipogenic cells derived from trappc9-deficient ASCs and marked differences in the distribution patterns and levels of calcium deposited in osteoblasts obtained from trappc9-null ASCs. Biochemical studies revealed that trappc9 deficiency resulted in an upregulated expression of rab1, rab11, and rab18, and agitated autophagy in ASCs. Moreover, we found that the content of neural stem cells in both the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus vastly declined in trappc9-null mice. Collectively, our results suggest that obesity, as well as brain structure hypoplasia induced by the deficiency of trappc9, involves an impairment in the plasticity of stem cells.

Adipose tissue is an abundant source of mesenchymal stem cells (ADMSCs). Evidence has suggested that depot-specific ADMSCs (obtained from subcutaneous or visceral adipose tissue-subADMSCs or visADMSCs, respectively) account for differential responses of each depot to metabolic challenges. However, little is known about the phenotype and changes in metabolism of the adipocytes derived from ADMSCs of obese individuals. Therefore, we investigated the phenotypic and metabolic characteristics, particularly the lipid profile, of fully differentiated adipocytes derived from ADMSCs of lean and obese (with/without metabolic syndrome) postmenopausal women. We observed a depot-specific pattern, with more pronounced changes present in the adipocytes obtained from subADMSCs. Namely, chronic oversupply of fatty acids (present in morbid obesity) triggered an increase in CD36/SR-B2 and FATP4 protein content (total and cell surface), which translated to an increased LCFA influx (3H-palmitate uptake). This was associated with the accumulation of TAG and DAG in these cells. Furthermore, we observed that the adipocytes of visADMSCs origin were larger and showed smaller granularity than their counterparts of subADMSCs descent. Although ADMSCs were cultured in vitro, in a fatty acids-deprived environment, obesity significantly influenced the functionality of the progenitor adipocytes, suggesting the existence of a memory effect.