Mesenchymal stem cell (MSC)-based therapies have yielded beneficial effects in a broad range of preclinical models and clinical trials for human diseases. In the context of MSC transplantation, it is widely recognized that the main mechanism for the regenerative potential of MSCs is not their differentiation, with in vivo data revealing transient and low engraftment rates. Instead, MSCs therapeutic effects are mainly attributed to its secretome, i.e., paracrine factors secreted by these cells, further offering a more attractive and innovative approach due to the effectiveness and safety of a cell-free product.

In this review, we will discuss the potential benefits of MSC-derived secretome in regenerative medicine with particular focus on respiratory, hepatic, and neurological diseases. Both free and vesicular factors of MSC secretome will be detailed. We will also address novel potential strategies capable of improving their healing potential, namely by delivering important regenerative molecules according to specific diseases and tissue needs, as well as non-clinical and clinical studies that allow us to dissect their mechanisms of action.

MSC-derived secretome includes both soluble and non-soluble factors, organized in extracellular vesicles (EVs). Importantly, besides depending on the cell origin, the characteristics and therapeutic potential of MSC secretome is deeply influenced by external stimuli, highlighting the possibility of optimizing their characteristics through preconditioning approaches. Nevertheless, the clarity around their mechanisms of action remains ambiguous, whereas the need for standardized procedures for the successful translation of those products to the clinics urges.

Myocardial infarction (MI) with resulting congestive heart failure is one of the leading causes of death worldwide. Current therapies for treating MI, such as devices, traditional medicine, and surgeries, come with many limitations as patients in their final stages of heart failure have little chances of experiencing any reversible changes. In recent decades, Mesenchymal stem cell (MSC) based therapy has become one of the most popular and rapidly developing fields in treating MI. Their supremacy for clinical applications is partially due to their unique properties and encouraging pre-clinical outcomes in various animal disease models. However, the majority of clinical trials registered for MSC therapy for diverse human diseases, including MI, have fallen short of expectations. This review intends to discuss the recent advances in the clinical application of using MSCs for cardiac repair and discuss challenges facing the clinical translation of MSCs for cardiac regeneration such as restoration of endothelial-cardiomyocyte crosstalk, immunomodulation and immune rejection, poor homing and migration, as well as low retention and survival. Furthermore, we will discuss recent strategies being investigated to help overcome some of these challenges.

Cell therapy utilizing mesenchymal stem cells, which have the ability to differentiate into different lineages, has garnered significant attention in recent years. Melissa officinalis is rich in biologically active compounds and exhibits antioxidant activity, antimicrobial properties, and sedative effects. Nanoemulsions can facilitate the effective transfer of substances and also protect drugs and biological materials from environmental factors. The aim of the present study is to investigate the role of Melissa officinalis extract nanoemulsion and the active ingredients of caffeic acid and quercetin as inducers in increasing the efficiency of differentiation of mesenchymal stem cells into neural cells in a laboratory environment.

Human WJMSCs were cultured in the basic culture medium consisting of: Hight glucose DMEM, 10 % FBS and 1 % penicillin/streptomycin. The alcoholic extract of Melissa officinalis was extracted and its nanoemulsion was prepared along with two other effective substances. Next, zeta potential and size of nanoparticles were measured by Dynamic light scattering (DLS) technique. The optimal dose of all three material was calculated by MTT (3-4,5-dimethylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide) assay and Acridine orange-ethidium bromide (AO/EB) staining. In the following, neural differentiation was investigated using Real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) and immunocytochemistry (ICC) techniques on days 7 and 14.

The results obtained from MTT and AO/EB assays showed that the optimal dose of nanoemulsion M. officinalis, caffeic acid and quercetin is 150 μg/ml, 75 μg/ml and 25 μg/ml, respectively. The ideal particle size for nanoemulsion is below 100 nm. The zeta potential of the M. officinalis extract nanoemulsion was reported to be -9.45 and the average particle size was 17.76 nm. The results of this study indicated that the expression of neural marker genes (MAP-2, β-tubulin III and NSE) and proteins (MAP-2, β-tubulin III and Gamma-enolase) increased in differentiated cells treated with the synthesized nanoemulsion compared to the control group on days 7 and 14 (P ≤ 0.05).

In general, our results showed that M. officinalis extract nanoemulsion, caffeic acid and quercetin caused induction of neural differentiation mechanism in human WJ-MSCs.

The role of cancer cell metabolic reprogramming in the formation and maintenance of cancer stem cells (CSCs) has been well established. This reprogramming involves alterations in the metabolic pathways of cancer cells, leading to the acquisition of stem cell-like properties such as self-renewal and differentiation. This study aimed to investigate the potential effects of bone marrow mesenchymal stem cells (BM-MSCs) on the enrichment of breast CSCs. Exosomes (Exo) and conditioned media (CM) were isolated from BM-MSCs for use in this experimental study. The impact of BM-MSCs-Exo and BM-MSCs-CM on the expression of stemness genes NANOG and OCT-4, as well as CD24 and CD44 markers, was assessed in MCF-7 and MDA-MB-231 cell cultures to identify CSCs. Furthermore, the effects of BM-MSCs-Exo and BM-MSCs-CM on cancer cell metabolism were evaluated by examining changes in glycolysis, the pentose phosphate pathway (PPP), and amino acid profiles. Additionally, the influence of BM-MSCs-Exo and BM-MSCs-CM on tumor growth in vivo was also investigated. The analysis of stemness marker expression in cells treated with BM-MSCs-Exo and BM-MSCs-CM revealed an increase in stemness characteristics compared to the control group. Furthermore, the examination of changes in cell metabolism following these treatments showed alterations in glycolysis, PPP, and amino acid metabolism pathways. Additionally, it was demonstrated that BM-MSCs-Exo and BM-MSCs-CM can promote tumor growth in mice following transplantation of 4T1 cells. These findings suggest that BM-MSCs-Exo and BM-MSCs-CM can enrich the population of CSCs in MCF-7 and MDA-MB-231 cells by targeting metabolic pathways, however, further studies are required to elicit the exact mechanisms of these phenomena.

Many patients struggle to control glucose without side effects. Due to their immunomodulatory and regenerative properties, mesenchymal stem cells (MSCs) might treat Diabetes Mellitus (DM). The authors employed this meta-analysis to evaluate the efficacy and safety of umbilical cord MSCs (UCMSCs) for DM management.

The PubMed, Cochrane, WOS, Embase, and Scopus databases were searched for randomized controlled trials (RCTs) investigating the effects of UCMSCs on DM (Types 1, 2) till January 2024. Patient demographics, interventions, and outcomes, including glycated hemoglobin (HbA1c%), C-peptide levels, and insulin requirements, were extracted. A comprehensive meta-analysis software was used.

Eight CTs of 334 patients (172 experimental and 162 controls) were included. UMSCs treatment substantially lowered HbA1c levels (MD = -1.06, 95% CI [-1.27, -0.85], p < 0.00001) with consistent outcomes (i2 = 0%, p = 0.43). Fasting C-peptide levels were heterogeneous but favored placebo (MD = 0.35, 95% CI [0.15, 0.56], p = 0.0007). In T1D patients, daily insulin requirements decreased considerably (MD = -0.24, 95% CI [-0.29, -0.18], p < 0.00001), with heterogeneity addressed by sensitivity analysis.

UMSCs therapy reduced HbA1c and insulin requirements, and increased C-peptide levels. Multicenter clinical trials are required to confirm the long-term efficacy and safety of UMSC therapy.

In recent years, the therapeutic utility of mesenchymal stem cells (MSCs) has received substantial attention from investigators, owing to their pleiotropic properties. The emerging insights from the developments in tissue engineering provide perspectives for the repair of damaged tissue and the replacement of failing organs. Perivascular cells including MSC-like pericytes, vascular smooth muscles, and other cells located around blood vessels, have been acknowledged to contribute to in situ angiogenesis and repair process. MSCs offer a wide array of therapeutic applications in different pathological states. However, in the current article, we have highlighted the recent updates on MSCs and their key applications in cardiac and cerebrovascular diseases, evident in different preclinical and clinical studies. We believe the present article would assist the investigators in understanding the recent advances of MSCs and exploring their therapeutic potential in varied ailments, especially cardiac and cerebrovascular diseases.

Traumatic brain injury (TBI) is a complex condition involving mechanisms that lead to brain dysfunction and nerve damage, resulting in significant morbidity and mortality globally. Affecting ~50 million people annually, TBI's impact includes a high death rate, exceeding that of heart disease and cancer. Complications arising from TBI encompass concussion, cerebral hemorrhage, tumors, encephalitis, delayed apoptosis, and necrosis. Current treatment methods, such as pharmacotherapy with dihydropyridines, high-pressure oxygen therapy, behavioral therapy, and non-invasive brain stimulation, have shown limited efficacy. A comprehensive understanding of vascular components is essential for developing new treatments to improve blood vessel-related brain damage. Recently, mesenchymal stem cells (MSCs) have shown promising results in repairing and mitigating brain damage. Studies indicate that MSCs can promote neurogenesis and angiogenesis through various mechanisms, including releasing bioactive molecules and extracellular vesicles (EVs), which help reduce neuroinflammation. In research, the distinctive characteristics of MSCs have positioned them as highly desirable cell sources. Extensive investigations have been conducted on the regulatory properties of MSCs and their manipulation, tagging, and transportation techniques for brain-related applications. This review explores the progress and prospects of MSC therapy in TBI, focusing on mechanisms of action, therapeutic benefits, and the challenges and potential limitations of using MSCs in treating neurological disorders.

Treatment with mesenchymal stem cells (MSCs) is a new promising therapeutic approach with substantial very auspicious potential. They have been shown to protect various played a role in protecting organs from damage. This current study aims to evaluate the impact of the treatment of olive leaf extract (OLE), bone marrow-derived (BM-MSCs), and their combination on hepatotoxicity in pregnant rats with diabetes.

Animals were divided into five groups (10 pregnant rats each) as follows: control, GDM group, and OLE group (rats received streptozotocin (STZ) at a dose of 35 mg/kg body weight). GD + OLE set (pregnant rats were administered OLE at a dose of 200 mg extract/kg of body weight). GD + MSCs group (pregnant rats treated with MSCs). GD + OLE + MSCs group (pregnant rats were treated with both MSCs and OLE).

STZ induced significant changes in liver parameters, lipid profile, and oxidative stress. Treatment with OLE, BM-MSCs, and their combination significantly ameliorated STZ-induced liver damage and oxidative stress. STZ resulted in a significant change in liver parameters, lipid profile, and oxidative stress. OLE, BM-MSC, and combination have significantly improved STZ-induced deterioration in liver and improved oxidative stress.

The findings demonstrate that OLE and BM-MSCs have beneficial effects in mitigating diabetes-related liver alterations. These outcomes showed that OLE and BM-MSC have beneficial effects in alleviating diabetes-related alterations in the liver.

The mesenchymal stem/stromal cells (MSCs) are multipotent cells that were initially discovered in the bone marrow in the late 1960s but have so far been discovered in almost all tissues of the body. The multipotent property of MSCs enables them to differentiate into various cell types and lineages, such as adipocytes, chondrocytes, and osteocytes. The immunomodulation capacity and tumor-targeting features of MSCs made their use crucial for cell-based therapies in cancer treatment, yet limited advancement could be observed in translational medicine prospects due to the need for more information regarding the controversial roles of MSCs in crosstalk tumors. In this review, we discuss the therapeutic potential of MSCs, the controversial roles played by MSCs in cancer progression, and the anticancer therapeutic strategies that are in association with MSCs. Finally, the clinical trials designed for the direct use of MSCs for cancer therapy or for their use in decreasing the side effects of other cancer therapies are also mentioned in this review to evaluate the current status of MSC-based cancer therapies.

Stem cells are capable of self-renewal and differentiation into specialised types. They range from totipotent cells to multipotent or somatic stem cells and ultimately to unipotent cells. Some adult multipotent stem cells can have the potential to regenerate and colonise diverse tissues. The respiratory airways and lung mucosa, exposed to ambient air, perform vital roles for all human tissues and organs. They serve as barriers against airborne threats and are essential for tissue oxygenation. Despite low steady-state turnover, lungs are vulnerable to injuries and diseases from environmental exposure. Lung stem cells are crucial due to their regenerative potential and ability to replace damaged cells. Lung repair with extrapulmonary stem cells can occur, leading to the coexistence of respiratory cells with different genetic origins, a phenomenon known as airway epithelial chimerism. The impact of such chimerism in lung repair and disease is actively studied. This review explores different stem cell types, focusing on pulmonary stem cells. It discusses airway epithelium models derived from stem cells for studying lung diseases and examines lung chimerism, particularly in lung transplantation and haematopoietic stem cell transplantation, highlighting its significance in understanding tissue repair and chimerism-mediated repair processes in lung pathology.

Mesenchymal stromal cells (MSCs) are a heterogeneous population of non-hematopoietic adult stem cells derived from the embryonic mesoderm. They possess self-renewal and multipotent differentiation capabilities, allowing them to give rise to mesodermal cell types, such as osteoblasts, chondroblasts, and adipocytes, as well as non-mesodermal cells, including neuron-like cells and endothelial cells. MSCs play a vital role in maintaining homeostasis across various tissues by facilitating tissue repair, immune regulation, and inflammatory response balance. Initially identified in bone marrow, MSCs have since been found in multiple tissues, including muscle, adipose tissue, and dental pulp, and are characterized by specific surface markers and differentiation abilities.Aging induces cellular senescence, an irreversible growth arrest linked to various stressors, which has significant implications for regenerative medicine. While initially viewed as a protective mechanism against tumorigenesis, the accumulation of senescent cells, particularly in MSCs, leads to age-related diseases through the senescence-associated secretory phenotype (SASP). The onset of senescence in MSCs diminishes their therapeutic potential and contributes to homeostatic imbalance. Key drivers of MSC senescence include genetic damage, noncoding RNA, and mitochondrial dysfunction, among others.This study outlines the principal methodologies for the isolation and characterization of MSCs, alongside techniques to induce acute senescence via hydrogen peroxide or irradiation, as well as replicative senescence, to investigate senescence-related changes in vitro. Understanding the mechanisms of MSC senescence will provide critical insights into the molecular pathways of aging and pave way for advancements in cellular therapies targeting age-related diseases.

Recently, it has been reported that mesenchymal stem cell (MSC)-derived humoral factors promote skin wound healing. As these humoral factors are transiently stored in cytoplasm, we collected them as part of the cell extracts from MSCs (MSC-ext). This study aimed to investigate the effects of MSC-ext on skin wound healing. We examined the effects of MSC-ext on cell proliferation and migration. Additionally, the effect of MSC-ext on skin wound healing was evaluated using a mouse skin defect model. The MSC-ext enhanced the proliferation of dermal fibroblasts, epithelial cells, and endothelial cells. It also increased the number of migrating fibroblasts and epithelial cells. The skin defects treated with MSC-ext demonstrated rapid wound closure compared to those treated with phosphate-buffered saline. The MSC-ext group exhibited a thicker dermis, larger Picrosirius red-positive areas, and a higher number of Ki67-positive cells. Our results indicate that MSC-ext promotes the proliferation and/or migration of fibroblasts, epithelial cells, and endothelial cells, and enhances skin wound healing. This suggests the therapeutic potential of MSC-ext in treating skin defects as a novel cell-free treatment modality.

This comprehensive overview of the historical milestones in cell culture underscores key breakthroughs that have shaped the field over time. It begins with Wilhelm Roux's seminal experiments in the 1880s, followed by the pioneering efforts of Ross Granville Harrison, who initiated groundbreaking experiments that fundamentally shaped the landscape of cell culture in the early 20th century. Carrel's influential contributions, notably the immortalization of chicken heart cells, have marked a significant advancement in cell culture techniques. Subsequently, Johannes Holtfreter, Aron Moscona, and Joseph Leighton introduced methodological innovations in three-dimensional (3D) cell culture, initiated by Alexis Carrel, laying the groundwork for future consolidation and expansion of the use of 3D cell culture in different areas of biomedical sciences. The advent of induced pluripotent stem cells by Takahashi and Yamanaka in 2006 was revolutionary, enabling the reprogramming of differentiated cells into a pluripotent state. Since then, recent innovations have included spheroids, organoids, and organ-on-a-chip technologies, aiming to mimic the structure and function of tissues and organs in vitro, pushing the boundaries of biological modeling and disease understanding. In this review, we overview the history of cell culture shedding light on the main discoveries, pitfalls and hurdles that were overcome during the transition from 2D to 3D cell culture techniques. Finally, we discussed the future directions for cell culture research that may accelerate the development of more effective and personalized treatments.

As people's living standards continue to improve and human life span expectancy increases, the incidence and mortality rates of breast cancer are continuously rising. Early detection of breast cancer and targeted therapy for different breast cancer subtypes can significantly reduce the mortality rate and alleviate the suffering of patients. Exosomes are extracellular vesicles secreted by various cells in the body. They participate in physiological and pathological responses by releasing active substances and play an important role in regulating intercellular communication. In recent years, research on exosomes has gradually expanded, and their special membrane structure and targetable characteristics are being increasingly applied in various clinical studies. Mesenchymal stem cells (MSCs)-derived exosomes play an important role in regulating the progression of breast cancer. In this review, we summarize the current treatment methods for breast cancer, the connection between MSCs, exosomes, and breast cancer, as well as the application of exosomes derived from MSCs from different sources in cancer treatment. We highlight how the rational design of modified MSCs-derived exosomes (MSCs-Exos) delivery systems can overcome the uncertainties of stem cell therapy and overcome the clinical translation challenges of nanomaterials. This work aims to promote future research on the application of MSCs-Exos in breast cancer treatment.

Bone tissue provides structural support for our bodies, with the inner bone marrow (BM) acting as a hematopoietic organ. Within the BM tissue, two types of stem cells play crucial roles: mesenchymal stem cells (MSCs) (or skeletal stem cells) and hematopoietic stem cells (HSCs). These stem cells are intricately connected, where BM-MSCs give rise to bone-forming osteoblasts and serve as essential components in the BM microenvironment for sustaining HSCs. Despite the mid-20th century proposal of BM-MSCs, their in vivo identification remained elusive owing to a lack of tools for analyzing stemness, specifically self-renewal and multipotency. To address this challenge, Cre/loxP-based cell lineage tracing analyses are being employed. This technology facilitated the in vivo labeling of specific cells, enabling the tracking of their lineage, determining their stemness, and providing a deeper understanding of the in vivo dynamics governing stem cell populations responsible for maintaining hard tissues. This review delves into cell lineage tracing studies conducted using commonly employed genetically modified mice expressing Cre under the influence of LepR, Gli1, and Axin2 genes. These studies focus on research fields spanning long bones and oral/maxillofacial hard tissues, offering insights into the in vivo dynamics of stem cell populations crucial for hard tissue homeostasis.

Mesenchymal stromal cells (MSCs) showed promising potential for regenerative and therapeutic applications for several pathologies and conditions. Their potential is mainly ascribed to the factors and extracellular vesicles (EVs) they release, which are now envisioned as cell-free therapeutics in cutting-edge clinical studies. A main cornerstone is the preferential uptake by target cells and tissues, in contrast to clearance by phagocytic cells or removal from circulation before reaching the final destination. Recent literature has suggested how the surface properties of EVs might influence their half-life, bio-distribution, and specific uptake. In particular, the concept of a protein corona surrounding EVs emerged. Especially for culture-purified EVs, the process of tailoring a treatment or tissue-specific corona was explored. Liam-Or et al. examined the impact of protein corona on MSC-EVs when specific proteins, preferentially albumin, were adsorbed from media on the EV surface before isolation. This resulted in improved uptake by liver parenchymal cells and reduced incorporation by macrophages, together with an increased half-life in the circulation system. Thus, producing MSC-EVs with an albumin-enriched protein corona might be a camouflage strategy to enhance non-phagocytic uptake in the liver. This research might be a milestone for future studies on other EVs-camouflage approaches tailored to specific tissues and therapeutic applications.

In this editorial we comment on the article by Safwan M et al. We especially focused on the cardiac function restoration by the use of mesenchymal stem cells (MSCs) therapy for heart failure (HF), which has emerged as a new treatment approach as "Living Biodrugs". HF remains a significant clinical challenge due to the heart's inability to pump blood effectively, despite advancements in medical and device-based therapies. MSCs have emerged as a promising therapeutic approach, offering benefits beyond traditional treatments through their ability to modulate inflammation, reduce fibrosis, and promote endogenous tissue regeneration. MSCs can be derived from various tissues, including bone marrow and umbilical cord. Umbilical cord-derived MSCs exhibit superior expansion capabilities, making them an attractive option for HF therapy. Conversely, bone marrow-derived MSCs have been extensively studied for their potential to improve cardiac function but face challenges related to cell retention and delivery. Future research is focusing on optimizing MSC sources, enhancing differentiation and immune modulation, and improving delivery methods to overcome current limitations.

Telomeres are pivotal determinants of cell stemness, organismal aging, and lifespan. Herein, we examined similarities in telomeres of Arabidopsis thaliana, mice, and humans. We report the common traits, which include their composition in multimers of TTAGGG sequences and their protection by specialized proteins. Moreover, given the link between telomeres, on the one hand, and cell proliferation and stemness on the other, we discuss the counterintuitive convergence between plants and mammals in this regard, focusing on the impact of niches on cell stemness. Finally, we suggest that tackling the study of telomere function and cell stemness by taking into consideration both plants and mammals can aid in the understanding of interconnections and contribute to research focusing on aging and organismal lifespan determinants.

Mesenchymal stem cells (MSC) are fibroblast-like non-hematopoietic cells with self-renewal and differentiation capacity, and thereby great potential in regeneration and wound healing. MSC populations are heterogeneous not only inherently, but also among different model species. In particular, porcine MSC serve as a frequently used resource for translational research, due to pigs' distinctive closeness to human anatomy and physiology. However, information on gene expression profiles from porcine MSC and its dynamics during differentiation is sparse, especially with regard to cell surface and inner cell markers. In this study, we investigated the transcriptome of bone marrow-derived MSC and its differentiated cell types in a minipig breed for experimental research, known as Mini-LEWE, using bulk mRNA sequencing. Our data highlighted Rap1 signaling and downstream pathways PI3K-Akt and MAPK signaling as potential players for the maintenance of stemness of BM-MSC. In addition, we were able to link the process of differentiation to changes in the regulation of actin cytoskeleton. A total of 18 "BM-MSC differentiation driver markers" were identified, potentially promoting the process of differentiation into adipocytes, chondrocytes as well as osteocytes. Our results offer a new perspective on the molecular phenotype of porcine BM-MSC and the transcriptional responses in new differentiated progeny.

Alzheimer's disease (AD) remains a progressive neurodegenerative disease with no cure. Treatment of AD relies on administering drugs that only subside the symptoms. In recent studies, mesenchymal stem cell (MSC)-exosomes have been marked to possess therapeutic potential for treating AD. This study aims to systematically review and analyse findings that focus on the isolation, characterisation, and sources of MSC-derived exosomes used to unravel the therapeutic potential of these exosomes targeting AD using in vitro and in vivo models. It is hypothesised that MSC-exosomes exhibit high therapeutic potential for AD treatment by exerting various modes of action. PubMed, Scopus, and Medline were used to find relevant published works from January 2016 until December 2020, using assigned keywords including "Alzheimer's disease", "secretome", and "exosomes". Only research articles meeting the predefined inclusion/exclusion criteria were selected and analysed. The risk of bias was assessed using the Office of Health Assessment and Translation tool (OHAT). A total of 17 eligible in vivo and in vitro studies were included in this review. Bone marrow-derived stem cells (BMSCs) were the most used source for exosome isolation, even though studies on exosomes from adipose-derived stem cells (ADSCs) and human umbilical cord stem cells (HUCSCs) provide more information on the characteristics. When the risk of bias was assessed, the studies presented various levels of biases. Notably, the in vitro and in vivo studies revealed neuroprotective properties of MSC-exosomes through different modes of action to alleviate AD pathology. Our review discovered that most MSC exosomes could degrade Aβ plaques, enhance neurogenesis, extenuate neuroinflammatory response through microglial activation, regulate apoptosis and reduce oxidative stress. Delivery of exosomal micro-RNAs was also found to reduce neuroinflammation. Findings from this review provided convincing systematic evidence highlighting the therapeutic properties of MSC-derived exosomes as a prospective source for cell-free (acellular) therapy in treating AD.

Mesenchymal stem cells (MSCs) are naturally-derived regenerative materials that exhibit significant potential in regenerative medicine. Previous studies have demonstrated that MSCs-based therapy can improve heart function in ischemia-injured hearts, offering an exciting therapeutic intervention for myocardial ischemic infarction, a leading cause of worldwide mortality and disability. However, the efficacy of MSCs-based therapies is significantly disturbed by the myocardial microenvironment, which undergoes substantial changes following ischemic injury. After the ischemic injury, blood vessels become obstructed and damaged, and cardiomyocytes experience ischemic conditions. This activates the hypoxia-induced factor 1 (HIF-1) pathway, leading to the rapid production of several cytokines and chemokines, including vascular endothelial growth factor (VEGF) and stromal-derived factor 1 (SDF-1), which are crucial for angiogenesis, cell migration, and tissue repair, but it is not sustainable. MSCs respond to these cytokines and chemokines by homing to the injured site and participating in myocardial regeneration. However, the deteriorated microenvironment in the injured myocardium poses challenges for cell survival, interacting with MSCs, and constraining their homing, retention, and migration capabilities, thereby limiting their regenerative potential. This review discusses how the deteriorated microenvironment negatively affects the ability of MSCs to promote myocardial regeneration. Recent studies have shown that optimizing the microenvironment through the promotion of angiogenesis can significantly enhance the efficacy of MSCs in treating myocardial infarction. This approach harnesses the full therapeutic potential of MSCs-based therapies for ischemic heart disease.

Advances in stem cell technology offer new possibilities for patients with untreated diseases and disorders. Stem cell-based therapy, which includes multipotent mesenchymal stem cells (MSCs), has recently become important in regenerative therapies. MSCs are multipotent progenitor cells that possess the ability to undergo in vitro self-renewal and differentiate into various mesenchymal lineages. MSCs have demonstrated promise in several areas, such as tissue regeneration, immunological modulation, anti-inflammatory qualities, and wound healing. Additionally, the development of specific guidelines and quality control methods that ultimately result in the therapeutic application of MSCs has been made easier by recent advancements in the study of MSC biology. This review discusses the latest clinical uses of MSCs obtained from the umbilical cord (UC), bone marrow (BM), or adipose tissue (AT) in treating various human diseases such as pulmonary dysfunctions, neurological disorders, endocrine/metabolic diseases, skin burns, cardiovascular conditions, and reproductive disorders. Additionally, this review offers comprehensive information regarding the clinical application of targeted therapies utilizing MSCs. It also presents and examines the concept of MSC tissue origin and its potential impact on the function of MSCs in downstream applications. The ultimate aim of this research is to facilitate translational research into clinical applications in regenerative therapies.

Mesenchymal stromal cells (MSCs) can be isolated from various tissues of healthy or patient donors to be retransplanted in cell therapies. Because the number of MSCs obtained from biopsies is typically too low for direct clinical application, MSC expansion in cell culture is required. However, ex vivo amplification often reduces the desired MSC regenerative potential and enhances undesired traits, such as activation into fibrogenic myofibroblasts. Transiently activated myofibroblasts restore tissue integrity after organ injury by producing and contracting extracellular matrix into scar tissue. In contrast, persistent myofibroblasts cause excessive scarring-called fibrosis-that destroys organ function. In this review, we focus on the relevance and molecular mechanisms of myofibroblast activation upon contact with stiff cell culture plastic or recipient scar tissue, such as hypertrophic scars of large skin burns. We discuss cell mechanoperception mechanisms such as integrins and stretch-activated channels, mechanotransduction through the contractile actin cytoskeleton, and conversion of mechanical signals into transcriptional programs via mechanosensitive co-transcription factors, such as YAP, TAZ, and MRTF. We further elaborate how prolonged mechanical stress can create persistent myofibroblast memory by direct mechanotransduction to the nucleus that can evoke lasting epigenetic modifications at the DNA level, such as histone methylation and acetylation. We conclude by projecting how cell culture mechanics can be modulated to generate MSCs, which epigenetically protected against myofibroblast activation and transport desired regeneration potential to the recipient tissue environment in clinical therapies.

Mesenchymal stem cells (MSCs) and macrophages collaboratively contribute to bone regeneration after injury. However, detailed mechanisms underlying the interaction between MSCs and inflammatory macrophages (M1) remain unclear. A macrophage-depleted tooth extraction model was generated in 5-wk-old female C57BL/6J mice using clodronate liposome (12.5 mg/kg/mouse, intraperitoneally) or saline injection (control) before maxillary first molar extraction. Mice were sacrificed on days 1, 3, 5, 7, and 10 after tooth extraction (n = 4). Regenerated bone volume evaluation of tooth extraction socket (TES) and histochemical analysis of CD80+M1, CD206+M2 (anti-inflammatory macrophages), PDGFRα+MSC, and TNF-α+ cells were performed. In vitro, isolated MSCs with or without TNF-α stimulation (10 ng/mL, 24 h, n = 3) were bulk RNA-sequenced (RNA-Seq) to identify TNF-α stimulation-specific MSC transcriptomes. Day 7 micro-CT and HE staining revealed significantly lower mean bone volume (clodronate vs control: 0.01 mm3 vs 0.02 mm3, p<.0001) and mean percentage of regenerated bone area per total TES in clodronate group (41.97% vs 54.03%, p<.0001). Clodronate group showed significant reduction in mean number of CD80+, TNF-α+, PDGFRα+, and CD80+TNF-α+ cells on day 5 (306.5 vs 558.8, p<.0001; 280.5 vs 543.8, p<.0001; 365.0 vs 633.0, p<.0001, 29.0 vs 42.5, p<.0001), while these cells recovered significantly on day 7 (493.3 vs 396.0, p=.0004; 479.3 vs 384.5, p=.0008; 593.0 vs 473.0, p=.0010, 41.0 vs 32.5, p=.0003). RNA-Seq analysis showed that 15 genes (|log2FC| > 5.0, log2TPM > 5) after TNF-α stimulation were candidates for regulating MSC's immunomodulatory capacity. In vivo, Clec4e and Gbp6 are involved in inflammation and bone formation. Clec4e, Gbp6, and Cxcl10 knockdown increased osteogenic differentiation of MSCs in vitro. Temporal reduction followed by apparent recovery of TNF-α-producing M1 macrophages and MSCs after temporal macrophage depletion suggests that TNF-α activated MSCs during TES healing. In vitro mimicking the effect of TNF-α on MSCs indicated that there are 15 candidate MSC genes for regulation of immunomodulatory capacity.

Regenerative medicine, specifically bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP), has become a novel adjunct that orthopedic surgeons have started to use with surgical rotator cuff repairs (RCR). Thus, we are conducting this systematic review to determine if either RCRs with BMAC alone or with BMAC and PRP result in superior functional outcomes. We conducted a comprehensive search using five databases including PubMed, Web of Science, Embase, Scopus, and Cochrane. After duplicates were removed, 1205 studies were screened by title and abstract using Rayyan, resulting in three included studies (one BMAC with PRP and two BMAC only). Only studies that reported functional outcomes using the American Shoulder and Elbow Surgeons Shoulder Score and the University of California Los Angeles Shoulder Score were included. Changes in assessment scores from baseline to follow-up evaluation were quantified using the effect size and used in the meta-analysis for each group. Interpretation of treatment efficacy was represented using Cohen's d. The effect size of BMAC with PRP (Cohen's d = 2.19) was not significantly different (p = 0.76) from that of BMAC alone (Cohen's d = 2.35). Between-group differences in functional outcomes were Cohen's d = 0.16, which was not significant. Given the lack of superiority and the small sample size, more research is required before a conclusion can be drawn as to the benefits of combining PRP with BMAC for RCR. If functional outcomes are the same, using BMAC alone as an adjunct may be optimal to reduce resources used and cost. Future studies should be conducted with a larger pool as our primary limitation is that only three studies were included.

Pluripotent stem cells are defined as cells that can generate cells of lineages from all three germ layers, ectoderm, mesoderm, and endoderm. On the contrary, unipotent and multipotent stem cells develop into one or more cell types respectively, but their differentiation is limited to the cells present in the tissue of origin or, at most, from the same germ layer. Multipotent and unipotent stem cells have been isolated from a variety of adult tissues, Instead, the presence in adult tissues of pluripotent stem cells is a very debated issue. In the early embryos, all cells are pluripotent. In mammalians, after birth, pluripotent cells are maintained in the bone-marrow and possibly in gonads. In fact, pluripotent cells were isolated from marrow aspirates and cord blood and from cultured bone-marrow stromal cells (MSCs). Only in few cases, pluripotent cells were isolated from other tissues. In addition to have the potential to differentiate toward lineages derived from all three germ layers, the isolated pluripotent cells shared other properties, including the expression of cell surface stage specific embryonic antigen (SSEA) and of transcription factors active in the early embryos, but they were variously described and named. However, it is likely that they are part of the same cell population and that observed diversities were the results of different isolation and expansion strategies. Adult pluripotent stem cells are quiescent and self-renew at very low rate. They are maintained in that state under the influence of the "niche" inside which they are located. Any tissue damage causes the release in the blood of inflammatory cytokines and molecules that activate the stem cells and their mobilization and homing in the injured tissue. The inflammatory response could also determine the dedifferentiation of mature cells and their reversion to a progenitor stage and at the same time stimulate the progenitors to proliferate and differentiate to replace the damaged cells. In this review we rate articles reporting isolation and characterization of tissue resident pluripotent cells. In the attempt to reconcile observations made by different authors, we propose a unifying picture that could represent a starting point for future experiments.

In recent years, cell therapy has provided desirable properties for promising new drugs. Mesenchymal stem cells are promising candidates for developing genetic engineering and drug delivery strategies due to their inherent properties, including immune regulation, homing ability and tumor tropism. The therapeutic potential of mesenchymal stem cells is being investigated for cancer therapy, inflammatory and fibrotic diseases, among others. Mesenchymal stem cells are attractive cellular carriers for synthetic nanoparticles for drug delivery due to their inherent homing ability. In this review, we comprehensively discuss the various genetic and non-genetic strategies of mesenchymal stem cells and their derivatives in drug delivery, tumor therapy, immune regulation, tissue regeneration and other fields. In addition, we discuss the current limitations of stem cell therapy and the challenges in clinical translation, aiming to identify important development areas and potential future directions.

Mesenchymal stem cells (MSCs) have promising potential for bone tissue engineering in bone healing and regeneration. They are regarded as such due to their capacity for self-renewal, multiple differentiation, and their ability to modulate the immune response. However, changes in the molecular pathways and transcription factors of MSCs in osteogenesis can lead to bone defects and metabolic bone diseases. DNA methylation is an epigenetic process that plays an important role in the osteogenic differentiation of MSCs by regulating gene expression. An increasing number of studies have demonstrated the significance of DNA methyltransferases (DNMTs), Ten-eleven translocation family proteins (TETs), and MSCs signaling pathways about osteogenic differentiation in MSCs. This review focuses on the progress of research in these areas.

This study aimed to identify osteoporosis-related core genes using bioinformatics analysis and machine learning algorithms.

mRNA expression profiles of osteoporosis patients were obtained from the Gene Expression Profiles (GEO) database, with GEO35958 and GEO84500 used as training sets, and GEO35957 and GSE56116 as validation sets. Differential gene expression analysis was performed using the R software "limma" package. A weighted gene co-expression network analysis (WGCNA) was conducted to identify key modules and modular genes of osteoporosis. Kyoto Gene and Genome Encyclopedia (KEGG), Gene Ontology (GO), and gene set enrichment analysis (GSEA) were performed on the differentially expressed genes. LASSO, SVM-RFE, and RF machine learning algorithms were used to screen for core genes, which were subsequently validated in the validation set. Predicted microRNAs (miRNAs) from the core genes were also analyzed, and differential miRNAs were validated using quantitative real-time PCR (qPCR) experiments.

A total of 1280 differentially expressed genes were identified. A disease key module and 215 module key genes were identified by WGCNA. Three core genes (ADAMTS5, COL10A1, KIAA0040) were screened by machine learning algorithms, and COL10A1 had high diagnostic value for osteoporosis. Four core miRNAs (has-miR-148a-3p, has-miR-195-3p, has-miR-148b-3p, has-miR-4531) were found by intersecting predicted miRNAs with differential miRNAs from the dataset (GSE64433, GSE74209). The qPCR experiments validated that the expression of has-miR-195-3p, has-miR-148b-3p, and has-miR-4531 was significantly increased in osteoporosis patients.

This study demonstrated the utility of bioinformatics analysis and machine learning algorithms in identifying core genes associated with osteoporosis.

The secretome, comprising bioactive chemicals released by mesenchymal stem cells (MSCs), holds therapeutic promise in regenerative medicine. This review aimed to explore the therapeutic potential of the MSC secretome in regenerative urology, particularly for treating erectile dysfunction (ED), and to provide an overview of preclinical and clinical research on MSCs in ED treatment and subsequently to highlight the rationales, mechanisms, preclinical investigations, and therapeutic potential of the MSC secretome in this context.

The review incorporated an analysis of preclinical and clinical research involving MSCs in the treatment of ED. Subsequently, it delved into the existing knowledge regarding the MSC secretome, exploring its therapeutic potential. The methods included a comprehensive examination of relevant literature to discern the processes underlying the therapeutic efficacy of the MSC secretome.

Preclinical research indicated the effectiveness of the MSC secretome in treating various models of ED. However, the precise mechanisms of its therapeutic efficacy remain unknown. The review provided insights into the anti-inflammatory, pro-angiogenic, and trophic properties of the MSC secretome. It also discussed potential advantages, such as avoiding issues related to cellular therapy, including immunogenicity, neoplastic transformation, and cost.

This review underscores the significant therapeutic potential of the MSC secretome in regenerative urology, particularly for ED treatment. While preclinical studies demonstrate promising outcomes, further research is essential to elucidate the specific mechanisms underlying the therapeutic efficacy before clinical application. The review concludes by discussing future perspectives and highlighting the challenges associated with the clinical translation of the MSC secretome in regenerative urology.

Mesenchymal stem/stromal cells (MSCs), originating from the mesoderm, represent a multifunctional stem cell population capable of differentiating into diverse cell types and exhibiting a wide range of biological functions. Despite more than half a century of research, MSCs continue to be among the most extensively studied cell types in clinical research projects globally. However, their significant heterogeneity and phenotypic instability have significantly hindered their exploration and application. Single-cell sequencing technology emerges as a powerful tool to address these challenges, offering precise dissection of complex cellular samples. It uncovers the genetic structure and gene expression status of individual contained cells on a massive scale and reveals the heterogeneity among these cells. It links the molecular characteristics of MSCs with their clinical applications, contributing to the advancement of regenerative medicine. With the development and cost reduction of single-cell analysis techniques, sequencing technology is now widely applied in fundamental research and clinical trials. This study aimed to review the application of single-cell sequencing in MSC research and assess its prospects.

Mesenchymal stem cell (MSCs) therapy, as a rapidly developing area of medicine, holds great promise for the treatment of a variety of medical conditions. MSCs are multipotent stem cells that can be isolated from various tissues and could self-renew and differentiate. They secrete cytokines and trophic factors that create a regenerative microenvironment and have immunomodulatory properties. Although clinical trials have been conducted with MSCs in various diseases, concerns regarding the possibility of malignant transformation of these cells have been raised. The studies showed a higher rate of hematological malignancy and carcinogenesis in experimental models after MSC transplantation. The mechanisms underlying malignant transformation of MSCs are complex and not fully understood, but they are believed to involve the presence of special signaling molecules and alterations in cell behavior regulation pathways. Possible pathways that lead to MSCs' oncogenic transformation occur through two mechanisms: spontaneous and stimulated malignant transformation, including cell fusion, fusion proteins, and the tumor microenvironment. MSC-based therapies have the potential to revolutionize medicine, and addressing the issue of malignancy is crucial to ensure their safety and efficacy. Therefore, the purpose of the present review is to summarize the potential mechanisms of the malignant transformation of MSCs. [Figure: see text].

Mesenchymal stromal cell (MSC)-based advanced therapy medicinal products (ATMPs) are being tried in a vast range of clinical applications. These cells can be isolated from different donor tissues by using several methods, or they can even be derived from induced pluripotent stem cells or embryonic stem cells. However, ATMP heterogeneity may impact product identity and potency, and, consequently, clinical trial outcomes. In this review, we discuss these topics and the need to establish minimal criteria regarding the manufacturing of MSCs so that these innovative therapeutics may be better positioned to contribute to the advancement of regenerative medicine.

Mesenchymal stem cells (MSCs) have important research value and broad application prospects in cardiovascular diseases (CVDs). However, few bibliometric analyses on MSCs in cardiovascular diseases are available. This study aims to provide a thorough review of the cooperation and influence of countries, institutions, authors, and journals in the field of MSCs in cardiovascular diseases, with the provision of discoveries in the latest progress, evolution paths, frontier research hotspots, and future research trends in the regarding field.

The articles related to MSCs in cardiovascular diseases were retrieved from the Web of Science. The bibliometric study was performed by CiteSpace and VOSviewer, and the knowledge map was generated based on data obtained from retrieved articles.

In our study, a total of 4,852 publications launched before August 31, 2023 were accessed through the Web of Science Core Collection (WoSCC) database via our searching strategy. Significant fluctuations in global publications were observed in the field of MSCs in CVDs. China emerged as the nation with the largest number of publications, yet a shortage of high-quality articles was noted. The interplay among countries, institutions, journals and authors is visually represented in the enclosed figures. Importantly, current research trends and hotspots are elucidated. Cluster analysis on references has highlighted the considerable interest in exosomes, extracellular vesicles, and microvesicles. Besides, keywords analysis revealed a strong emphasis on myocardial infarction, therapy, and transplantation. Treatment methods-related keywords were prominent, while keywords associated with extracellular vesicles gathered significant attention from the long-term perspective.

MSCs in CVDs have become a topic of active research interest, showcasing its latent value and potential. By summarizing the latest progress, identifying the research hotspots, and discussing the future trends in the advancement of MSCs in CVDs, we aim to offer valuable insights for considering research prospects.

Mesenchymal stem cells are core to bone homeostasis and repair. They both provide the progenitor cells from which bone cells are formed and regulate the local cytokine environment to create a pro-osteogenic environment. Dysregulation of these cells is often seen in orthopaedic pathology and can be manipulated by the physician treating the patient. This narrative review aims to describe the common applications of cell therapies to bone healing whilst also suggesting the future direction of these techniques.

Studies regarding mesenchymal stem cells turned up in the 1960's and this cell type created a great number of questions about its functions and applicability in science and medicine. When used with therapeutic intent, these cells present an inclination to migrate to sites of injury, inflammation or disease, where they secrete bioactive factors that stimulates the synthesis of new tissue. In this context, studies using rodents reported that MSCs promoted positive effects in the ovarian function in mice with premature aging of follicular reserve. In female bovines, experimental stem cell-based therapies have been used to either generate new oocytes with in vitro quality or stimulate such action in vivo. It is also reported, that the intraovarian application of mesenchymal stem cells generates a greater production of embryos in vitro and the production of early and expanded blastocysts. Additionally, analysis of ovarian tissue in animal subjected to treatment showed an increase in the number of developing follicles. Nevertheless, the treatments involving stem cells with different modes of application, different sources and different species were able to act on the hormonal, tissue, cellular and metabolic levels, generating positive results in the recovery and improvement of ovarian functions.

Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) hold great therapeutic potential in regenerative medicine. Therefore, it is crucial to establish a Good Manufacturing Practice (GMP)-compliant methodology for the isolation and culture of WJ-MSCs. Through comprehensive research, encompassing laboratory-scale experiments to pilot-scale studies, we aimed to develop standardized protocols ensuring the high yield and quality of WJ-MSCs manufacturing.

Firstly, optimization of parameters for the enzymatic digestion method used to isolate WJ-MSCs was conducted. These parameters included enzyme concentrations, digestion times, seeding densities, and culture media. Additionally, a comparative analysis between the explant method and the enzymatic digestion method was performed. Subsequently, the consecutive passaging of WJ-MSCs, specifically up to passage 9, was evaluated using the optimized method. Finally, manufacturing processes were developed and scaled up, starting from laboratory-scale flask-based production and progressing to pilot-scale cell factory-based production. Furthermore, a stability study was carried out to assess the storage and use of drug products (DPs).

The optimal parameters for the enzymatic digestion method were a concentration of 0.4 PZ U/mL Collagenase NB6 and a digestion time of 3 h, resulting in a higher yield of P0 WJ-MSCs. In addition, a positive correlation between the weight of umbilical cord tissue and the quantities of P0 WJ-MSCs has been observed. Evaluation of different concentrations of human platelet lysate revealed that 2% and 5% concentrations resulted in similar levels of cell expansion. Comparative analysis revealed that the enzymatic digestion method exhibited faster outgrowth of WJ-MSCs compared to the explant method during the initial passage. Passages 2 to 5 exhibited higher viability and proliferation ability throughout consecutive passaging. Moreover, scalable manufacturing processes from the laboratory scale to the pilot scale were successfully developed, ensuring the production of high-quality WJ-MSCs. Multiple freeze-thaw cycles of the DPs led to reduced cell viability and viable cell concentration. Subsequent thawing and dilution of the DPs resulted in a significant decrease in both metrics, especially when stored at 20-27 °C.

This study offers valuable insights into optimizing the isolation and culture of WJ-MSCs. Our scalable manufacturing processes facilitate the large-scale production of high-quality WJ-MSCs. These findings contribute to the advancement of WJ-MSCs-based therapies in regenerative medicine.

Diabetes mellitus (DM) often causes chronic kidney damage despite best medical practices. Diabetic kidney disease (DKD) arises from a complex interaction of factors within the kidney and the whole body. Targeting specific disease-causing agents using drugs has not been effective in treating DKD. However, stem cell therapies offer a promising alternative by addressing multiple disease pathways and promoting kidney regeneration. Mesenchymal stem cells (MSCs) offer great promise due to their superior accessibility ratio from adult tissues and remarkable modes of action, such as the production of paracrine anti-inflammatory and cytoprotective substances. This review critically evaluates the development of MSC treatment for DKD as it moves closer to clinical application. Results from animal models suggest that systemic MSC infusion may positively impact DKD progression. However, few registered and completed clinical trials exist, and whether the treatments are effective in humans is still being determined. Significant knowledge gaps and research opportunities exist, including establishing the ideal source, dose, and timing of MSC delivery, better understanding of in vivo mechanisms, and developing quantitative indicators to obtain a more significant therapeutic response. This paper reviews recent literature on using MSCs in preclinical and clinical trials in DKD. Potent biomarkers related to DKD are also highlighted, which may help better understand MSCs' action in this disease progression. KEY MESSAGES: Mesenchymal stem cells have anti-inflammatory and paracrine effects in diabetic kidney disease. Mesenchymal stem cells alleviate in animal models having diabetic kidney disease. Mesenchymal stem cells possess promise for the treatment of diabetic kidney disease.

In the last few decades, mesenchymal stem cells (MSCs)-based regenerative therapies in clinical applications have gradually become a hot topic due to their long-term self-renewal and multilineage differentiation ability. In this scenario, placenta (p) has been considered as a good source of MSCs. As a tissue of fetal origin with abundant number of stem cells compared to other sources, their non-invasive acquisition, strong immunosuppression, and lack of ethical concerns make placenta an indispensable source of MSC in stem cell research and therapy. The mesenchymal stem cells were derived from human term placenta (p-MSCs) in xenofree condition using platelet lysate (PL) as a suitable alternative to fetal bovine serum (FBS). Upon isolation, p-MSCs showed plastic adherence with spindle-shaped, fibroblast-like morphology under microscope. p-MSCs flourished well in PL-containing media. Immunophenotyping showed classical MSC markers (> 90%) and lack expression of hematopoietic and HLA-DR (< 1%). Surprisingly, differentiation study showed differentiation of p-MSCs to mature adipocytes in both induced cells and control (spontaneous differentiation), as observed via oil red staining. This is in line with gene expression data where both control and induced cells were positive for visfatin and leptin. Thus, we propose that p-MSCs can be used for clinical applications in the treatment of various chronic and degenerative diseases.

Acute myocardial infarction (AMI) is the leading cause of cardiovascular death and remains the most common cause of heart failure. Reopening of the occluded artery, i.e., reperfusion, is the only way to save the myocardium. However, the expected benefits of reducing infarct size are disappointing due to the reperfusion paradox, which also induces specific cell death. These ischemia-reperfusion (I/R) lesions can account for up to 50% of final infarct size, a major determinant for both mortality and the risk of heart failure (morbidity). In this review, we provide a detailed description of the cell death and inflammation mechanisms as features of I/R injury and cardioprotective strategies such as ischemic postconditioning as well as their underlying mechanisms. Due to their biological properties, the use of mesenchymal stromal/stem cells (MSCs) has been considered a potential therapeutic approach in AMI. Despite promising results and evidence of safety in preclinical studies using MSCs, the effects reported in clinical trials are not conclusive and even inconsistent. These discrepancies were attributed to many parameters such as donor age, in vitro culture, and storage time as well as injection time window after AMI, which alter MSC therapeutic properties. In the context of AMI, future directions will be to generate MSCs with enhanced properties to limit cell death in myocardial tissue and thereby reduce infarct size and improve the healing phase to increase postinfarct myocardial performance.

The combination of cells and biomaterials has become a powerful approach to regenerative medicine in recent years. Understanding the in-vitro interactions between cells and biomaterials is crucial for the success of regenerative medicine.

In this study, we developed an AD-pectin/chitosan/nano-crystalline cellulose scaffold with nano-hydroxy-apatite (n-HAP) and alendronate (ALN). The second step was to evaluate its effect on the immunomodulatory properties and biological behaviors of seeded adipose-derived mesenchymal stem cells (ADSCs) for bone tissue repair.

After preparing and evaluating the characterization tests of the new combined n-HAP scaffold, we established different culture conditions to evaluate ADSC growth on this scaffold with or without ALN. The main assays were MTT assay, RT-PCR, and ELISA.

Our data regarding characterization tests (including SEM, TGA, FTIR, gelation time, swelling ratio, rheology and degradation tests) of ALN-loaded n-HAP scaffold showed the proper stability and good mechanical status of the scaffold. ADSC proliferation and viability increased in the presence of the scaffold compared with other conditions. Moreover, our data demonstrated increased gene expression and protein levels of anti-inflammatory TGF-β, HGF, and IDO cytokines in the presence of the ALN-loaded n-HAP scaffold, indicating the increased immunosuppressive activity of ADSCs in vitro.

This study demonstrates the promising abilities of the ALN-loaded n-HAP scaffold to increase the proliferation, viability, and immunomodulatory capacity of ADSCs, elucidating new aspects of cell-material interactions that can be used for bone tissue regeneration/repair, and paving the path of future research in developing new approaches for MSC- based therapy.

A traumatic brain injury (TBI) is a major health issue affecting many people across the world, causing significant morbidity and mortality. TBIs often have long-lasting effects, disrupting daily life and functionality. They cause two types of damage to the brain: primary and secondary. Secondary damage is particularly critical as it involves complex processes unfolding after the initial injury. These processes can lead to cell damage and death in the brain. Understanding how these processes damage the brain is crucial for finding new treatments. This review examines a wide range of literature from 2021 to 2023, focusing on biomarkers and molecular mechanisms in TBIs to pinpoint therapeutic advancements. Baseline levels of biomarkers, including neurofilament light chain (NF-L), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), Tau, and glial fibrillary acidic protein (GFAP) in TBI, have demonstrated prognostic value for cognitive outcomes, laying the groundwork for personalized treatment strategies. In terms of pharmacological progress, the most promising approaches currently target neuroinflammation, oxidative stress, and apoptotic mechanisms. Agents that can modulate these pathways offer the potential to reduce a TBI's impact and aid in neurological rehabilitation. Future research is poised to refine these therapeutic approaches, potentially revolutionizing TBI treatment.

A wound takes a long time to heal and involves several steps. Following tissue injury, inflammation is the primary cause of tissue regeneration and repair processes. As a result, the pathophysiological processes involving skin damage, healing, and remodeling depend critically on the control of inflammation. The fact that it is a feasible target for improving the prognosis of wound healing has lately become clear. Mesenchymal stem cells (MSCs) are an innovative and effective therapeutic option for wound healing due to their immunomodulatory and paracrine properties. By controlling the inflammatory milieu of wounds through immunomodulation, transplanted MSCs have been shown to speed up the healing process. In addition to other immunomodulatory mechanisms, including handling neutrophil activity and modifying macrophage polarization, there may be modifications to the activation of T cells, natural killer (NK) cells, and dendritic cells (DCs). Furthermore, several studies have shown that pretreating MSCs improves their ability to modulate immunity. In this review, we summarize the existing knowledge about how MSCs influence local inflammation in wounds by influencing immunity to facilitate the healing process. We also provide an overview of MSCs optimizing techniques when used to treat wounds.