Neurons, distributed throughout the body, regulate various bodily functions. The recovery of the nervous system is often slow and can be irreversible. Currently, the approach of using mesenchymal stem cells (MSCs) in conjunction with conventional treatments for nervous system injuries is being explored. Nanoemulsions are systems designed for the nanoscale delivery of drug cargoes. Foeniculum vulgare (F. vulgare), a medicinal plant long utilized in complementary medicine, is the focus of this study. The aim is to utilize nanoemulsions of fennel to induce the differentiation of MSCs into neural-like cells in vitro.

Human adipose-derived mesenchymal stem cells (hADSCs) were commercially purchased. These cells were cultured in DMEM medium containing 10 % fetal bovine serum and 1 % penicillin-streptomycin antibiotic. Based on a sequential extraction method, n-hexane (Hex), ethyl acetate (EtAc), and ethanolic extracts were obtained from the seeds of F. vulgare. To prepare the F. vulgare extract nanoemulsion, the aqueous phase (distilled water), the oily part (F. vulgare extract), Span 80 and Tween 20 were used. The optimal dose of F. vulgare nanoemulsion was determined using the MTT assay and acridine orange/ethidium bromide (AO/EB) staining. Neural differentiation was induced using a specialized differentiation medium on the MSCs, with the prepared nanoemulsions acting as inducers. The neural differentiation of the human differentiated hADSCs was studied and evaluated through Real-time PCR and immunocytochemistry (ICC) techniques on days 7 and 14.

The results obtained from the MTT and AO/EB tests indicated that the optimal dose of F. vulgare nanoemulsions is 1 μg/ml. Analysis of neural differentiation index gene expression revealed a significant (P ≤ 0.05) upregulation of MAP-2, β-tubulin III, and NSE genes on days 7 and 14 following treatment with the nanoemulsions. It is noteworthy that the nanoemulsion prepared from the hexane extract of the plant showed a significant increase in the expression of marker genes in the process of neural differentiation. Protein expression analysis demonstrated an increase in MAP-2, β-tubulin III, and NSE (gamma enolase) proteins in response to the nanoemulsion inducers compared to the control group (TCPS).

Overall, our findings indicate that F. vulgare nanoemulsions have a positive effect on the expression of genes and proteins related to neural differentiation in hADSCs. The proposed protocol may serve as a potential therapeutic strategy in complementary medicine for patients seeking to improve injuries to the nervous system. However, further studies and performance measurements are necessary in future research to confirm these results.

Adipose-derived stem cells (ADSCs) exhibit promising potential for the treatment of various diseases, including osteoarthritis. Spheroids derived from ADSCs are a viable treatment option with enhanced anti-inflammatory effects and tissue repair capabilities.

SphereRing® is a rotating donut-shaped tube that efficiently produces large quantities of spheroids. However, accurately measuring spheroid size for spheroid quality assessment is challenging. This study aimed to develop an automated method for measuring spheroid size using deep learning through the ChatGPT Data Analyst for image recognition and processing.

The area, perimeter, and circularity of spheroids generated with the SphereRing system were analyzed using ChatGPT Data Analyst and ImageJ. Measurement accuracy was validated using Bland-Altman analysis and scatter plot correlation coefficients.

ChatGPT Data Analyst was consistent with ImageJ for all parameters. Bland-Altman plots demonstrated strong agreement; most data points were within the 95% limits.

The ChatGPT Data Analyst provides a reliable and efficient alternative for assessing spheroid quality. This method reduces human error and improves reproducibility to enhance spheroid quality control. Thus, this method has potential applications in regenerative medicine.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Most current treatments for TBI and other neurological disorders focus on the brain, often overlooking the significant contributions of peripheral organs to disease progression. Emerging evidence suggests that organs such as the liver and adipose tissue play crucial roles in TBI pathogenesis. The liver synthesizes lipids and proteins vital for brain function, while adipose tissue provides hormones and metabolites that influence brain activity. New research indicates that the liver and adipose tissue work in concert with the hypothalamus to regulate essential processes, such as body temperature, which become disrupted in TBI. Additionally, the brain-peripheral axis-a complex network of visceral nerve pathways, hormones, and metabolites-plays a bidirectional role in regulating brain plasticity and function. Understanding how TBI leads to dysregulation of the liver, adipose tissue, and other organs could unlock new therapeutic opportunities for treating TBI and related neurological disorders. The intricate autonomic network involving hypothalamic and enteric neurons, along with visceral nerve pathways and hormones, presents both pathological targets and therapeutic potential. We examine scientific evidence suggesting that correcting disturbances in systemic physiology could enhance the brain's capacity for healing. However, the interdependence of this autonomic network implies that treating dysfunction in one area may affect others. Therefore, we also explore the mechanisms by which diet and exercise can comprehensively impact the brain-peripheral axis, supporting the healing process. CHEMICAL COMPOUNDS: D-Fructose (PubChem CID 2723872); docosahexaenoic acid (PubChem CID 45934466); eicosapentaenoic acid (PubChem 5282847).

Background: An autologous minimally manipulated homologous adipose tissue (AMHAT) fabricated using three-dimensional (3D) bioprinting has shown potential in the treatment of diabetic foot ulcers and other chronic wounds. Methods: This study assessed the efficacy of AMHAT fabricated using 3D bioprinting for treating skin defects after a wide excision of skin cancer lesions where primary closure was not feasible. A total of 10 consecutive patients were included. The wounds were photographed and analyzed using AI, and the fat tissue harvested from the lower abdomen was processed into an AMHAT patch using a 3D bioprinter. The wound area was measured weekly until complete wound closure was achieved. Results: The area of the skin defects ranged from 1.77-6.22 cm2, averaging 2.72 cm2. Complete closure was achieved in 3-5 (average, 4.2) weeks. The residual area decreased from 52% after 1 week to 3% after 4 weeks. The scar appearance was esthetically favorable, with one patient showing mild nostril asymmetry. Furthermore, patient-reported outcome evaluation using the Japanese version of SCAR-Q for postoperative scars showed a very high level of satisfaction. Conclusions: The 3D bioprinted AMHAT accelerates wound healing with minimal scarring, offering an important option for skin defects where esthetics are a priority.

Triple-negative breast cancer (TNBC) is one of the most aggressive and challenging subtypes for treatment, due to the lack of hormone receptors and the human epidermal growth factor receptor 2 (HER2) protein. The identification of new molecular targets is important for the development of targeted and specific therapies for TNBC patients. MicroRNAs (miRNAs) have emerged as promising molecular targets, being involved in cellular processes such as cell survival, apoptosis, differentiation, carcinogenesis, and metastasis. Extracellular vesicles (EVs) have gained prominence in areas such as drug delivery, immune modulation, biomarkers for diagnosis and prognosis, and therapeutics, due to their use as vehicles for the delivery of miRNAs, regulation of gene expression, and development of combined therapeutic strategies. In particular, mesenchymal stem cell-derived EVs (MSC-derived EVs) can transfer proteins, mRNAs/miRNAs, or DNA molecules and are being considered safer treatment options due to their inability to directly form tumors and contain lower amounts of membrane proteins such as MHC molecules. Numerous studies have highlighted the role of miRNAs in EVs in TNBC tumorigenesis, with a focus on diagnosis, prognosis, treatment selection, and monitoring. However, the development of therapies with EVs, especially MSC-derived EVs, is still in its infancy. Therefore, the aim of this review is to address new therapeutic strategies based on the delivery of miRNAs through EVs, with a focus on MSC-derived EVs, for the treatment of TNBC as an innovative therapy in oncology.

Current treatment of osteoarthritis (OA) mainly focused on treating symptoms. Exosome from Adipose-derived Mesenchymal Stem Cell (Ad-MSC) have been shown to delay degenerative process. This study aimed to investigate the clinical, radiological and histological impact of combined intra-articular (IA) hyaluronic acid (HA) and exosome Ad-MSCs in-vivo using a larger animal model with low-grade OA.

Eighteen male Ovies aries sheep underwent total lateral meniscectomy and conventional radiography was performed to confirm low-grade OA after 6 weeks. The sheep were divided into three groups, Group 1 (G1; n=6) received thrice exosome injections, G2 (n=6) received twice HA injection, and G3 (n=6) received both treatments with a 1-week interval after 10 days of meniscectomy. Clinical evaluations were conducted using the Clinical Lameness Score (CLS), radiographic with X-ray using OA score by Innes et al, while macroscopic evaluation by Osteoarthritis Research Society International (OARSI) scores.

Lameness parameter scored lowest in G3 significantly (2.0±0.0 VS 2.7±0.52 VS 2.7±0.52; p=0.024) at the second month although the overall CLS score did not significantly differ at the 3 rd month. The best improvement of conventional total OA radiographic score at the 3 rd month compared to all groups (5.2±1.17 vs 6.3±0.82 vs 6.7±1.03; p=0.053). Macroscopic OARSI evaluation showed no difference (p=0.711).

Combined repeated exosome Ad-MSC and HA IA injection proven to delay OA progression, however longer duration of follow up is required to evaluate its long-term effect.

Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapy due to their self-renewal capability, multilineage differentiation potential, and immunomodulatory effects. The molecular characteristics of MSCs are influenced by their location. Recently, epidural fat (EF) and EF-derived MSCs (EF-MSCs) have garnered attention due to their potential benefits to the spinal microenvironment and their high expression of neural SC markers. However, their clinical applications are limited due to cell senescence and limited accessibility of EF. Although many studies have attempted to establish an immortalized, stable SC line, the characteristics of immortalized EF-MSCs remain to be clarified.

To establish and analyze stable immortalized EF-MSCs.

The phenotypes of EF-MSCs were analyzed using optical microscopy. Cell immortalization was performed using lentiviral vectors. The biomolecular characteristics of the cells were analyzed by immunoblotting, quantitative PCR, and proteomics.

The immortalized EF-MSCs demonstrated a significantly extended lifespan compared to the control group, with well-preserved adipogenic potential and SC surface marker expression. Introduction of human telomerase reverse transcriptase genes markedly increased the lifespan of EF-MSCs. Proteomics analysis revealed substantial increase in the expression of DNA replication pathway components in immortalized EF-MSCs.

Immortalized EF-MSCs exhibited significantly enhanced proliferative capacity, retained adipogenic potential, and upregulated the expression of DNA replication pathway components.

Persistent reactive oxygen species (ROS) and neuroinflammation contribute to the onset and progression of neurodegenerative diseases, underscoring the need for targeted therapeutic strategies to mitigate these effects. Extracellular vesicles (EVs) show promise in drug delivery due to their biocompatibility, ability to cross biological barriers, and specific interactions with cell and tissue receptors. In this study, we demonstrated that human plasma-derived EVs (pEVs) exhibit higher brain-targeting specificity, while adipose-derived mesenchymal stem cells EVs (ADMSC-EVs) offer regenerative and immunomodulatory properties. We further investigated the potential of these EVs as therapeutic carriers for brain-targeted drug delivery, using Donepezil (DNZ) as the model drug. DNZ, a cholinesterase inhibitor commonly used for Alzheimer's disease (AD), also has neuroprotective and anti-inflammatory properties. The size of EVs used ranged from 50 to 300 nm with a surface charge below -30 mV. Both formulations showed rapid cellular internalization, without toxicity, and the ability to cross the blood-brain barrier (BBB) in a zebrafish model. The have analyzed the anti-inflammatory and antioxidant actions of pEVs-DNZ and ADMSC-EVs-DNZ in the presence of lipopolysaccharide (LPS). ADMSC-EVs significantly reduced the inflammatory mediators released by HMC3 microglial cells while treatment with pEVs-DNZ and ADMSC-EVs-DNZ lowered both phagocytic activity and ROS levels in these cells. In vivo experiments using zebrafish larvae revealed that both EV formulations reduced microglial proliferation and exhibited antioxidant effects. Overall, this study highlights the potential of EVs loaded with DNZ as a novel approach for treating neuroinflammation underlying various neurodegenerative diseases.

β-alanine (BA), being a non-proteinogenic amino acid, is an important constituent of L-carnosine (LC), which is necessary for maintaining the muscle buffering capacity and preventing a loss of muscle mass associated with aging effects. BA is also very important for normal human metabolism due to the formation of a part of pantothenate, which is incorporated into coenzyme A. BA is synthesized in the liver, and its combination with histidine results in the formation of LC, which accumulates in the muscles and brain tissues and has a well-defined physiological role as a good buffer for the pH range of muscles that caused its rapidly increased popularity as ergogenic support to sports performance. The main antioxidant mechanisms of LC include reactive oxygen species (ROS) scavenging and chelation of metal ions. With age, the buffering capacity of muscles also declines due to reduced concentration of LC and sarcopenia. Moreover, LC acts as an antiglycation agent, ultimately reducing the development of degenerative diseases. LC has an anti-inflammatory effect in autoimmune diseases such as osteoarthritis. As histidine is always present in the human body in higher concentrations than BA, humans have to get BA from dietary sources to support the required amount of this critical constituent to supply the necessary amount of LC synthesis. Also, BA has other beneficial effects, such as preventing skin aging and intestinal damage, improving the stress-- fighting capability of the muscle cells, and managing an age-related decline in memory and learning. In this review, the results of a detailed analysis of the role and various beneficial properties of BA and LC from the anti-aging perspective are presented.

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.

Infertility is a reproductive health problem in the male or female reproductive system. Traditional assisted reproductive technology (ART) has been unable to solve various cases of infertility for years. Clinical researchers have sought to treat infertility using new methods that are more effective and noninvasive than the old methods. Recently, Mesenchymal stem cells (MSCs) and MSCs-derived Exosomes (MSC-Exos) via paracrine activity play an important role in treating various causes of infertility and improving pregnancy outcomes. In this review, we focus on the roles of MSCs and MSC-Exos cell therapy in female infertility in the different types of female reproductive disorders.

The biological properties of human mesenchymal stromal cells (hMSCs) have been explored in over a thousand clinical trials in the last decade. Although hMSCs can be isolated from multiple sources, the degree of biological similarity between cell populations from these sources remains to be determined. A comparative study was performed investigating the growth kinetics and functionality of hMSCs isolated from adipose tissue (AT), bone marrow (BM) and umbilical cord tissue (UCT) expanded in monolayer over five passages. Adult hMSCs (AT, BM) had a slower proliferation ability than the UCT-hMSCs, with no apparent differences in their glucose consumption profile. BM-hMSCs produced higher concentrations of endogenous vascular endothelial growth factor (VEGF) compared to AT- and UCT-hMSCs. This study also revealed that UCT-hMSCs were more efficiently transduced by a lentiviral vector carrying a VEGF gene than their adult counterparts. Following cellular immunophenotypic characterization, no differences across the sources were found in the expression levels of the typical markers used to identify hMSCs. This work established a systematic approach for cell source selection depending on the hMSC's intended clinical application.

The tumor microenvironment (TME) harbors a hidden universe of interactions that profoundly shape the behavior of head and neck cancers (HNCs). HNCs are not merely localized afflictions; they constitute a pressing global health crisis that impacts millions, frequently resulting in severe prognoses due to late-stage diagnosis and intrinsic resistance to conventional therapies. In this intricate interplay, cancer cells function as strategic players, adeptly manipulating their microenvironment to foster proliferation, evade immune detection, and withstand therapeutic interventions. Central to this dynamic play are exosomes, the enigmatic pawns of cellular communication, carrying vital messages across the board. This review elucidates the multifaceted roles of exosomes within the TME, highlighting their capacity to transmit critical signals that not only promote tumor progression but also modulate immune responses, ultimately playing a crucial role in the evolving narrative of HNC. Our insights aim to catalyze further research and exploration into exosome-targeted therapies, potentially transforming the landscape of HNC treatment and improving clinical outcomes in this formidable battle against cancer.

Spinal cord injury (SCI) is a serious condition accompanied by severe adverse events that affect several aspects of the patient's life, such as motor, sensory, and functional impairment. Despite its severe consequences, definitive treatment for these injuries is still missing. Therefore, researchers have focused on developing treatment strategies aimed at ensuring full recovery post-SCI. Accordingly, attention has been drawn toward cellular therapy using mesenchymal stem cells. Considering their wide availability, decreased immunogenicity, wide expansion capacity, and impressive effectiveness in many therapeutic approaches, adipose-derived stem cell (ADSC) injections in SCI cases have been investigated and showed promising results. In this review, SCI pathophysiology and ADSC transplantation benefits are discussed independently, together with SCI animal models and adipose stem cell preparation and application techniques. The mechanisms of healing in an SCI post-ADSC injection, the outcomes of this therapeutic approach, and current clinical trials are also deliberated, in addition to the challenges and future perspectives, aiming to encourage further research in this field.

In regenerative medicine, the isolation of mesenchymal stromal cells (MSCs) from the adipose tissue's stromal vascular fraction (SVF) is a critical area of study. Our review meticulously examines the isolation process of MSCs, starting with the extraction of adipose tissue. The choice of liposuction technique, anatomical site, and immediate processing are essential to maintain cell functionality. We delve into the intricacies of enzymatic digestion, emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm. The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF, alongside cell viability assessments like flow cytometry, which are vital for confirming the efficacy of the isolated MSCs. We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources, touching upon immunocompatibility and logistical considerations, as well as the variability inherent in donor-derived cells. Anesthesia choices, the selection between hypodermic needles vs liposuction cannulas, and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation. Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF. The necessity for standardized MSC isolation protocols is highlighted, promoting reproducibility and successful clinical application. We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action, aiming to further the field of regenerative medicine. The review concludes with a call for rigorous research, interdisciplinary collaboration, and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.

Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to differentiate into multiple lineages including bone, cartilage, muscle and fat. They hold immunomodulatory properties and therapeutic ability to treat multiple diseases, including autoimmune and chronic degenerative diseases. In this article, we reviewed the different biological properties, applications and clinical trials of MSCs. Also, we discussed the basics of manufacturing conditions, quality control, and challenges facing MSCs in the clinical setting.

Extensive review of the literature was conducted through the databases PubMed, Google Scholar, and Cochrane. Papers published since 2015 and covering the clinical applications and research of MSC therapy were considered. Furthermore, older papers were considered when referring to pioneering studies in the field.

The most widely studied stem cells in cell therapy and tissue repair are bone marrow-derived mesenchymal stem cells. Adipose tissue-derived stem cells became more common and to a lesser extent other stem cell sources e.g., foreskin derived MSCs. MSCs therapy were also studied in the setting of COVID-19 infections, ischemic strokes, autoimmune diseases, tumor development and graft rejection. Multiple obstacles, still face the standardization and optimization of MSC therapy such as the survival and the immunophenotype and the efficiency of transplanted cells. MSCs used in clinical settings displayed heterogeneity in their function despite their extraction from healthy donors and expression of similar surface markers.

Mesenchymal stem cells offer a rising therapeutic promise in various diseases. However, their potential use in clinical applications requires further investigation.

Introduction: The purpose of this research was to test the impact of seeding a hydrogel chitosan scaffold (HCS) with human adipose-derived stem cells (hADSCs) under the influence of photobiomodulation (PBM) on the remodeling step on the wound repairing process in mice. Methods: Thirty mice were randomly assigned to five groups (n=6 per group ): The control group (group 1) consisted of mice without any intervention. In group 2, an HCS was implanted into the wound. In group 3, a combination of HCS+hADSC was inserted into the wound. In group 4, an HCS was inserted into the wound and PBM was applied. In group 5, a combination of HCS+hADSCs was inserted into the wound, followed by PBM treatment. Results: Improvements in the injury closing rate (WCR) and microbial flora were observed in all groups. However, the highest WCRs were observed in group s 5, 4, 3, and 2 (all P values were 0.000). Groups 3-5 showed increased wound strength compared to group s 1 and 2, with group 2 demonstrating better results than group 1 (P values ranged from 0.000 to 0.013). Although group s 3-5 showed increases in certain stereological elements compared to group s 1 and 2, group 2 exhibited superior results in comparison with group 1 (P values ranged from 0.000 to 0.049). Conclusion: The joined use of HCS+hADSCs+PBM significantly accelerated the wound healing process during the maturation phase in healthy mice. This approach demonstrated superior wound healing compared to the use of HCS alone, hADSCs+HCS, or PBM+HCS. The findings suggest an additive effect when HCS+hADSCs+PBM are combined.

Spheroids are spherical aggregates of cells that mimic the three-dimensional (3D) architecture of tissues more closely than traditional two dimensional (2D) cultures. Spheroids of adipose stem cells (SASCs) show special features such as high multilineage differentiation potential and immunomodulatory activity. These properties have been attributed to their secreted factors, such as cytokines and growth factors. Moreover, a key role is played by the extracellular vesicles (EVs), which lead a heterogeneous cargo of proteins, mRNAs, and small RNAs that interfere with the pathways of the recipient cells.

The aim of this work was to characterize the composition of the secretome and exosome from SASCs and evaluate their regenerative potential.

SASCs were extracted from adipose samples of healthy individuals after signing informed consent. The exosomes were isolated and characterized by Dinamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Western blotting analyses. The expression of mRNAs and miRNAs were evaluated through real-time PCR. Lastly, a wound-healing assay was performed to investigate their regenerative potential on different cell cultures.

The SASCs' exosomes showed an up-regulation of NANOG and SOX2 mRNAs, typical of stemness maintenance, as well as miR126 and miR146a, related to angiogenic and osteogenic processes. Moreover, the exosomes showed a regenerative effect.

The SASCs' secretome carried paracrine signals involved in stemness maintenance, pro-angiogenic and pro-osteogenic differentiation, immune system regulation, and regeneration.

Replacing damaged organs or tissues and repairing damage by tissue engineering are attracting great interest today. A potentially effective method for bone remodeling involves combining nanofiber scaffolds with extracellular matrix (ECM), and growth factors. Today, electrospun PCL-based scaffolds are widely used for tissue engineering applications.

In this study, we used an electrospun polycaprolactone (PCL) scaffold coated with fibronectin (Fn), a ubiquitous ECM glycoprotein, to investigate the induction potential of this scaffold in osteogenesis with adipose-derived mesenchymal stem cells (AD-MSCs).

Scanning electron microscopy (SEM) analysis showed that fibronectin, by binding to the membrane receptors of mesenchymal stem cells (MSCs), leads to their attachment and proliferation on the PCL scaffold and provides a suitable environment for osteogenesis. In addition, biochemical tests showed that fibronectin leads to increased calcium deposition. The results also showed that alkaline phosphatase activity was significantly higher in the PCL scaffold coated with fibronectin than in the control groups (PCL scaffold group and tissue culture polystyrene (TCPS) group) (P<0.05). Also, the analysis of quantitative reverse transcription PCR (qRT-PCR) data showed that the relative expression of bone marker genes such as osteonectin (ON), osteocalcin (OC), RUNX family transcription factor 2 (RUNX2), and collagen type I alpha 1 (COL1) was much higher in the cells seeded on the PCL/Fn scaffold than in the other groups (P<0.05).

The results show that fibronectin has an increasing effect in accelerating bone formation and promising potential for use in bone tissue engineering.

Neuronal injuries, as one of the consequences of sports-related incidents, exert a profound influence on the athletes' future, potentially leading to complete immobility and impeding their athletic pursuits. In cases of severe damage inflicted upon the spinal cord (SC) and peripheral nervous systems (PNS), the regenerative process is notably compromised, rendering it essentially inefficient. Among the pivotal therapeutic approaches for the enhancement and prevention of secondary SC injuries (SCI), stem cell transplantation (SCT) stands out prominently. Stem cells, whether directly involved in replacement and reconstruction or indirectly through modification and secretion of crucial bioenvironmental factors, engage in the intricate process of tissue regeneration. Stem cells, through the secretion of neurotrophic factors (NTFs) (aiming to modulate the immune system), reduction of inflammation, axonal growth stimulation, and myelin formation, endeavor to facilitate the regeneration of damaged SC tissue. The fundamental challenges of this approach encompass the proper selection of suitable stem cell candidates for transplantation and the establishment of an appropriate microenvironment conducive to SC repair. In this article, an attempt has been made to explore sports-related injuries, particularly SCI, to comprehensively review innovative methods for treating SCI, and to address the existing challenges. Additionally, some of the stem cells used in neural injuries and the process of their utilization have been discussed.

Dental tissue engineering is an alternative procedure for restoring damaged dental tissues. Adipose-derived stem cells are a new source of cells for regenerative endodontics in combination with scaffold materials. The descriptive data about this regenerative process is still insufficient.

To evaluate the regenerative potential of Adipose-derived stem cells using a self-assembling polypeptide scaffold for the dentin-pulp complex in an emptied root canal space.

40 root segments of human single-rooted teeth were transplanted into the albino rats' dorsal subcutaneous tissue. Root segments were divided into two groups: group I contained only a self-assembling polypeptide scaffold, and group II contained fluorescent-labeled Adipose-derived stem cells embedded in a self-assembling polypeptide scaffold. The newly formed tissues were assessed on the 60th and 90th days post-transplantation using routine histological examination, Masson trichrome staining, and scanning electron microscopy.

Group I showed granulation tissue without any signs of predentin formation or odontoblast-like cells. Group II revealed the presence of predentin tissue along the dentin margin, with arranged odontoblast-like cells. An organized connective tissue with abundant vasculature and calcific masses was observed in the pulp space.

Adipose-derived stem cells can be considered as alternative stem cells for regenerating the dentin-pulp complex. Dentin pulp complex regeneration utilizing a self-assembling polypeptide scaffold alone would not yield successful results.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterised by the formation of a hyperplastic pannus, as well as cartilage and bone damage. The pathogenesis of RA is complex and involves broad interactions between various cells present in the inflamed synovium, including fibroblast-like synoviocytes (FLSs), macrophages, and T cells, among others. Under inflammatory conditions, these cells are activated, further enhancing inflammatory responses and angiogenesis and promoting bone and cartilage degradation. Novel treatment methods for RA are greatly needed, and mesenchymal stromal cells (MSCs) have been suggested as a promising new regenerative and immunomodulatory treatment. In this paper, we present the interactions between MSCs and RA-FLSs, and macrophages and T cells, and summarise studies examining the use of MSCs in preclinical and clinical RA studies.

Mesenchymal stem cells (MSCs) isolated from Wharton's jelly (WJ-MSCs) and adipose tissue (AD-MSCs) are alternative sources for bone marrow-derived MSCs. Owing to their multiple functions in angiogenesis, immune modulation, proliferation, migration, and nerve regeneration, MSC-derived exosomes can be applied in "cell-free cell therapy". Here, we investigated the functional protein components between the exosomes from WJ-MSCs and AD-MSCs to explain their distinct functions. Proteins of WJ-MSC and AD-MSC exosomes were collected and compared based on iTRAQ gel-free proteomics data. Results: In total, 1695 proteins were detected in exosomes. Of these, 315 were more abundant (>1.25-fold) in AD-MSC exosomes and 362 kept higher levels in WJ-MSC exosomes, including fibrinogen proteins. Pathway enrichment analysis suggested that WJ-MSC exosomes had higher potential for wound healing than AD-MSC exosomes. Therefore, we treated keratinocyte cells with exosomes and the recombinant protein of fibrinogen beta chain (FGB). It turned out that WJ-MSC exosomes better promoted keratinocyte growth and migration than AD-MSC exosomes. In addition, FGB treatment had similar results to WJ-MSC exosomes. The fact that WJ-MSC exosomes promoted keratinocyte growth and migration better than AD-MSC exosomes can be explained by their higher FGB abundance. Exploring the various components of AD-MSC and WJ-MSC exosomes can aid in their different clinical applications.

In this review, we delve into the intricate relationship between white adipose tissue (WAT) remodeling and metabolic aspects in obesity, with a specific focus on individuals with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). WAT is a highly heterogeneous, plastic, and dynamically secreting endocrine and immune organ. WAT remodeling plays a crucial role in metabolic health, involving expansion mode, microenvironment, phenotype, and distribution. In individuals with MHO, WAT remodeling is beneficial, reducing ectopic fat deposition and insulin resistance (IR) through mechanisms like increased adipocyte hyperplasia, anti-inflammatory microenvironment, appropriate extracellular matrix (ECM) remodeling, appropriate vascularization, enhanced WAT browning, and subcutaneous adipose tissue (SWAT) deposition. Conversely, for those with MUO, WAT remodeling leads to ectopic fat deposition and IR, causing metabolic dysregulation. This process involves adipocyte hypertrophy, disrupted vascularization, heightened pro-inflammatory microenvironment, enhanced brown adipose tissue (BAT) whitening, and accumulation of visceral adipose tissue (VWAT) deposition. The review underscores the pivotal importance of intervening in WAT remodeling to hinder the transition from MHO to MUO. This insight is valuable for tailoring personalized and effective management strategies for patients with obesity in clinical practice.

Surgery, burns or surgery-free accident are leading causes of scars with altered tissue consistency, a reduced degree of motion and pain. Autologous fat grafting can dramatically improve tissue consistency and elasticity but less frequently results in the reduction of pain. Therefore, we analyzed different cell populations present within the adipose tissue to be engrafted and correlated them with the reduction of pain after surgery. Here, we identify a population of CD3 - CD4 - CD304 + cells present in grafted adipose tissue, whose abundance highly correlates with pain improvement shortly after surgery ( r2 = 0.7243****) as well as persistently over time (3 months later: r2 = 0.6277****, 1 year later: r2 = 0.5346***, and 4 years later: r2 = 0.5223***). These cells are characterized by the absence of the hematopoietic marker CD45, whereas they express CD90 and CD34, which characterize mesenchymal stem cells (MSCs); the concomitant presence of CD10 and CD73 in the plasma membrane supports a function of these cells in pain reduction. We deduce that the enrichment of this adipose tissue-derived MSC subset could enhance the therapeutic properties of adipose grafts and ameliorate localized pain syndromes.

Cardiovascular diseases (CVDs) are the leading cause of death and include several vascular and cardiac disorders, such as atherosclerosis, coronary artery disease, cardiomyopathies, and heart failure. Multiple treatment strategies exist for CVDs, but there is a need for regenerative treatment of damaged heart. Stem cells are a broad variety of cells with a great differentiation potential that have regenerative and immunomodulatory properties. Multiple studies have evaluated the efficacy of stem cells in CVDs, such as mesenchymal stem cells and induced pluripotent stem cell-derived cardiomyocytes. These studies have demonstrated that stem cells can improve the left ventricle ejection fraction, reduce fibrosis, and decrease infarct size. Other studies have investigated potential methods to improve the survival, engraftment, and functionality of stem cells in the treatment of CVDs. The aim of the present review is to summarize the current evidence on the role of stem cells in the treatment of CVDs, and how to improve their efficacy.

Chronic foot ulcers are the leading cause of prolonged hospitalization and loss of social participation in people with diabetes. Conventional management of diabetic foot ulcers (DFU) is associated with slow healing, high cost, and recurrent visits to the hospital. Currently, the application of autologous lipotransfer is more popular, as the regenerative and reparative effects of fat are well established. Herein we report the efficacy of minimally manipulated extracellular matrix (MA-ECM) prepared from autologous homologous adipose tissue by using 3D bioprinting in DFU (test group) in comparison to the standard wound care (control group). A total of 40 subjects were screened and randomly divided into test and control groups. In the test group, the customized MA-ECM was printed as a scaffold from the patient autologous fat using a 3D bioprinter device and applied to the wound directly. The control group received standard wound care and weekly follow-up was done for all the patients. We evaluated the efficacy of this novel technology by assessing the reduction in wound size and attainment of epithelialization. The patients in the test group (n = 17) showed complete wound closure with re-epithelialization approximately within a period of 4 weeks. On the other hand, most of the patients in the control group (n = 16) who received standard wound dressings care showed a delay in wound healing in comparison to the test group. This technique can be employed as a personalized therapeutic method to accelerate diabetic wound healing and may provide a promising potential alternative approach to protect against lower foot amputation a most common complication in diabetes.

Spinal cord injuries (SCI) lead to functional alteration with important consequences such as motor and sensory disorders. The repair strategies developed to date remain ineffective. The adipose tissue-derived stromal vascular fraction (SVF) is composed of a cocktail of cells with trophic, pro-angiogenic and immunomodulatory effects. Numerous therapeutic benefits were shown for tissue reconstitution, peripheral neuropathy and for the improvement of neurodegenerative diseases. Here, the therapeutic efficacy of SVF on sensorimotor recovery after an acute thoracic spinal cord contusion in adult rats was determined.

Male Sprague Dawley rats (n = 45) were divided into 3 groups: SHAM (without SCI and treatment), NaCl (animals with a spinal lesion and receiving a saline injection through the dura mater) and SVF (animals with a spinal lesion and receiving a fraction of fat removed from adipocytes through the dura mater). Some animals were sacrificed 14 days after the start of the experiment to determine the inflammatory reaction by measuring the interleukin-1β, interleukin-6 and Tumor Necrosis Factor-α in the lesion area. Other animals were followed once a week for 12 weeks to assess functional recovery (postural and locomotor activities, sensorimotor coordination). At the end of this period, spinal reflexivity (rate-dependent depression of the H-reflex) and physiological adjustments (ventilatory response to metabosensitive muscle activation following muscle fatigue) were measured with electrophysiological tools.

Compared to non-treated animals, results indicated that the SVF reduced the endogenous inflammation and increased the behavioral recovery in treated animals. Moreover, H-reflex depression and ventilatory adjustments to muscle fatigue were found to be comparable between SHAM and SVF groups.

Our results highlight the effectiveness of SVF and its high therapeutic potential to improve sensorimotor functions and to restore the segmental sensorimotor loop and the communication between supra- and sub-lesional spinal cord regions after traumatic contusion.

Small-scale clinical trials have provided evidence suggesting the effectiveness of stem-cell therapy (SCT) for patients diagnosed with Crohn's disease (CD). The objective of the research was to systematically assess the effectiveness and safety of SCT for individuals diagnosed with CD through a comprehensive review and meta-analysis.

A search was conducted in Medline (PubMed), CENTER (Cochrane Library), and Embase (Ovid) to find randomized controlled trials (RCTs) that assessed the impact of SCT on the occurrence of clinical remission (CR) and severe adverse events (SAE) among patients diagnosed with CD. The Cochrane Q test and estimation of I2 were used to assess heterogeneity among studies. After incorporating heterogeneity, a random-effects model was employed for data pooling.

Overall, 12 RCTs involving 632 adult patients with medically refractory CD or CD-related fistula were included. In comparison with placebo or no treatment, SCT showed a greater likelihood of CR (odds ratio [OR] 2.08, 95% CI 1.39-3.12, p < 0.001) without any notable heterogeneity (I2 = 0%). Consistent results were observed in subgroup analyses based on study design, patient diagnosis, source and type of stem cells, and follow-up durations, with all p-values for subgroup analyses being greater than 0.05. The occurrence of SAE was similar among patients assigned to SCT and the placebo/no treatment cohorts (OR 0.70, 95% CI 0.37-1.33, p = 0.28; I2 = 0%).

For patients with medically refractory CD or CD-related fistula, SCT may be an alternatively effective and safe treatment.

Articular cartilage is a highly specialized tissue able to tolerate physical stress. However, its capacity for restoration is restricted, and injuries to the cartilage do not recover spontaneously. Interest in mesenchymal stem cells derived from human adipose tissue (hASCs) is growing due to their potential to improve tissue healing and recovery. Decellularized extracellular matrix (dECM)-based hydrogels combined with hASCs could serve as an interface for studying behavior and differentiation properties in a cartilage microenvironment. In the present study, we described the behavior of hASCs cultured in a commercial dECM MatriXpec™. The structural microtopography of MatriXpec™ was analyzed by scanning electron micrography, and its protein composition was accessed by mass spectrometry. The protein composition of MatriXpec™ is mainly represented by collagen proteins, building its fibrous ultrastructure. hASCs were cultured three-dimensionally (3D) on MatriXpec™ to perform cell viability, growth, and cartilage differentiation analysis. We showed that MatriXpec™ could be loaded with hASCs and that it supports cell maintenance for several days. We observed that the three-dimensional ultrastructure of the biomaterial is composed of nanofibers, and its protein composition reflects the tissue from which it was harvested. Finally, we showed that the molecular cues from the hydrogel are biologically active as these influence cell behavior and differentiation phenotype, increasing the expression of fibrocartilage-related genes such as SOX9, COL1, COL10, and MMP13. MatriXpec™ hydrogel can be used as an interface for 3D hASCs culture studies as it maintains cell viability and supports its differentiation process.

Aging-associated cardiovascular diseases depend on the longitudinal deterioration of stem cell dynamics. The entire mechanism behind it is not completely understood. However, many studies suggest that endocrine pathways, particularly the insulin-like growth factor-1(IGF1) signaling pathway are involved in cardioprotection, especially in stem-cell treatments. Here, we investigated the role of a co-chaperone, carboxyl-terminus of Hsp70 interacting protein (CHIP) in the aspects of growth factor secretion and receptor stabilization in mesenchymal stem cells (MSCs). Briefly, we overexpressed CHIP in rat adipose-derived stem cells (rADSCs) and explored the consequences in vitro, and in vivo, in spontaneously hypertensive rats (SHR). Our data revealed that CHIP overexpression in rADSCs promoted the secretion of insulin-like growth factor-1 (IGF1) and IGF binding protein-3 (IGFBP3) as per immunoblot/cytokine array analysis. We also found that these results were dependent on the nuclear translocation of signal transducer and activator of transcription 3 (STAT3) in rADSCs. Further, the CHIP co-chaperone was also involved in the stabilization of the receptor of IGF1 (IGF1R); interactions between the beta transmembrane region of IGF1R, and the tetracopeptide repeat (TPR) domain of CHIP were evident. Importantly, after the transplantation of lentiviral CHIP overexpression of rADSCs (rADSCsCHIP-WT) into nine months aging-SHR led to an increase in their cardiac function - increased ejection fraction and fractional shortening (≈15% vs. control SHR) - as well as a decrease in their heart size and heart rate, respectively. Altogether, our results support the use of CHIP overexpressing stem cells for the mitigation of cardiac hypertrophy and remodeling associated with late-stage hypertension.

Successful stem cell applications could have a significant impact on the medical field, where many lives are at stake. However, the translation of stem cells to the clinic could be improved by overcoming challenges in stem cell transplantation and in vivo retention at the site of tissue damage. This review aims to showcase the most recent insights into developing hydrogels that can deliver, retain, and accommodate stem cells for tissue repair. Hydrogels can be used for tissue engineering, as their flexibility and water content makes them excellent substitutes for the native extracellular matrix. Moreover, the mechanical properties of hydrogels are highly tuneable, and recognition moieties to control cell behaviour and fate can quickly be introduced. This review covers the parameters necessary for the physicochemical design of adaptable hydrogels, the variety of (bio)materials that can be used in such hydrogels, their application in stem cell delivery and some recently developed chemistries for reversible crosslinking. Implementing physical and dynamic covalent chemistry has resulted in adaptable hydrogels that can mimic the dynamic nature of the extracellular matrix.

Crohn's disease (CD) is an inflammatory bowel disease that can affect any part of the intestine. There is currently no recognized cure for CD because its cause is unknown. One of the modern approaches that have been suggested for the treatment of CD and other inflammatory-based disorders is cell therapy.

Search terms were stem cell therapy, CD, adipose-derived stem cells, mesenchymal stem cells, and fistula. Of 302 related studies, we removed duplicate and irrelevant papers and identified the ones with proper information related to our scope of the research by reviewing all the abstracts and categorizing each study into the proper section.

Nowadays, stem cell therapy is widely implied in treating CD. Although mesenchymal and adipose-derived tissue stem cells proved to be safe in treating Crohn's-associated fistula, there are still debates on an optimal protocol to use. Additionally, there is still a lack of evidence on the efficacy of stem cell therapy for intestinal involvement of CD. Future investigations should focus on preparing a standard protocol as well as luminal stem cell therapy in patients.

In recent decades, bone tissue engineering, which is supported by scaffold, seed cells and bioactive molecules (BMs), has provided new hope and direction for treating bone defects. In terms of seed cells, compared to bone marrow mesenchymal stem cells, which were widely utilized in previous years, adipose-derived stem cells (ADSCs) are becoming increasingly favored by researchers due to their abundant sources, easy availability and multi-differentiation potentials. However, there is no systematic theoretical basis for selecting appropriate biomaterials loaded with ADSCs. In this review, the regulatory effects of various biomaterials on the behavior of ADSCs are summarized from four perspectives, including biocompatibility, inflammation regulation, angiogenesis and osteogenesis, to illustrate the potential of combining various materials with ADSCs for the treatment of bone defects. In addition, we conclude the influence of additional application of various BMs on the bone repair effect of ADSCs, in order to provide more evidences and support for the selection or preparation of suitable biomaterials and BMs to work with ADSCs. More importantly, the associated clinical case reports and experiments are generalized to provide additional ideas for the clinical transformation and application of bone tissue engineering loaded with ADSCs.

Wound healing is a complex and meticulously orchestrated process involving multiple phases and cellular interactions. This narrative review explores the intricate mechanisms behind wound healing, emphasizing the significance of cellular processes and molecular factors. The phases of wound healing are discussed, focusing on the roles of immune cells, growth factors, and extracellular matrix components. Cellular shape alterations driven by cytoskeletal modulation and the influence of the 'Formin' protein family are highlighted for their impact on wound healing processes. This review delves into the use of absorbable meshes in wound repair, discussing their categories and applications in different surgical scenarios. Interleukins (IL-2 and IL-6), CD31, CD34, platelet rich plasma (PRP), and adipose tissue-derived mesenchymal stem cells (ADSCs) are discussed in their respective roles in wound healing. The interactions between these factors and their potential synergies with absorbable meshes are explored, shedding light on how these combinations might enhance the healing process. Recent advances and challenges in the field are also presented, including insights into mesh integration, biocompatibility, infection prevention, and postoperative complications. This review underscores the importance of patient-specific factors and surgical techniques in optimizing mesh placement and healing outcomes. As wound healing remains a dynamic field, this narrative review provides a comprehensive overview of the current understanding and potential avenues for future research and clinical applications.

Spinal cord injury (SCI) is an as yet untreatable neuropathology that causes severe dysfunction and disability. Cell-based therapies hold neuroregenerative and neuroprotective potential, but, although being studied in SCI patients for more than two decades, long-term efficacy and safety remain unproven, and which cell types result in higher neurological and functional recovery remains under debate. In a comprehensive scoping review of 142 reports and registries of SCI cell-based clinical trials, we addressed the current therapeutical trends and critically analysed the strengths and limitations of the studies. Schwann cells, olfactory ensheathing cells (OECs), macrophages and various types of stem cells have been tested, as well as combinations of these and other cells. A comparative analysis between the reported outcomes of each cell type was performed, according to gold-standard efficacy outcome measures like the ASIA impairment scale, motor and sensory scores. Most of the trials were in the early phases of clinical development (phase I/II), involved patients with complete chronic injuries of traumatic aetiology and did not display a randomized comparative control arm. Bone marrow stem cells and OECs were the most commonly tested cells, while open surgery and injection were the main methods of delivering cells into the spinal cord or submeningeal spaces. Transplantation of support cells, such as OECs and Schwann cells, resulted in the highest ASIA Impairment Scale (AIS) grade conversion rates (improvements in ∼40% of transplanted patients), which surpassed the spontaneous improvement rate expected for complete chronic SCI patients within 1 year post-injury (5-20%). Some stem cells, such as peripheral blood-isolated and neural stem cells, offer potential for improving patient recovery. Complementary treatments, particularly post-transplantation rehabilitation regimes, may contribute highly to neurological and functional recovery. However, unbiased comparisons between the tested therapies are difficult to draw, given the great heterogeneity of the design and outcome measures used in the SCI cell-based clinical trials and how these are reported. It is therefore crucial to standardize these trials when aiming for higher value clinical evidence-based conclusions.

Mesenchymal stem cells (MSCs) are regarded as highly promising cells for allogeneic cell therapy, owing to their multipotent nature and ability to display potent and varied functions in different diseases. The functions of MSCs, including native immunomodulation, high self-renewal characteristic, and secretory and trophic properties, can be employed to improve the immune-modulatory functions in diseases. MSCs impact most immune cells by directly contacting and/or secreting positive microenvironmental factors to influence them. Previous studies have reported that the immunomodulatory role of MSCs is basically dependent on their secretion ability from MSCs. This review discusses the immunomodulatory capabilities of MSCs and the promising strategies to successfully improve the potential utilization of MSCs in clinical research.

Photobiomodulation (PBM)-the irradiation of tissue with low-intensity light-mitigates neuropathology in rodent models of Parkinson's disease (PD) when targeted at the head ('transcranial PBM'). In humans, however, attenuation of light energy by the scalp and skull necessitates a different approach. We have reported that targeting PBM at the body also protects the brain by a mechanism that spreads from the irradiated tissue ('remote PBM'), although the optimal peripheral tissue target for remote PBM is currently unclear. This study compared the neuroprotective efficacy of remote PBM targeting the abdomen or leg with transcranial PBM, in mouse and non-human primate models of PD. In a pilot study, the neurotoxin MPTP was used to induce PD in non-human primates; PBM (670 nm, 50 mW/cm2 , 6 min/day) of the abdomen (n = 1) was associated with fewer clinical signs and more surviving midbrain dopaminergic cells relative to MPTP-injected non-human primates not treated with PBM. Validation studies in MPTP-injected mice (n = 10 per group) revealed a significant rescue of midbrain dopaminergic cells in mice receiving PBM to the abdomen (~80%, p < .0001) or legs (~80%, p < .0001), with comparable rescue of axonal terminals in the striatum. Strikingly, this degree of neuroprotection was at least as, if not more, pronounced than that achieved with transcranial PBM. These findings confirm that remote PBM provides neuroprotection against MPTP-induced destruction of the key circuitry underlying PD, with both the abdomen and legs serving as viable remote targets. This should provide the impetus for a comprehensive investigation of remote PBM-induced neuroprotection in other models of PD and, ultimately, human patients.

Chronic endometritis (CE) is closely linked to the reproductive failure. Exosome (Exo)-based therapy is proposed as an encouraging strategy in inflammation-related disorders; however, little work has been devoted to its usage in CE therapy. An in vitro CE was established by administration of lipopolysaccharide (LPS) in human endometrial stromal cells (HESCs). The cell proliferation, cell apoptosis, and inflammatory cytokine assays were performed in vitro, and the efficacy of Exos derived from adipose tissue-derived stem cells (ADSCs) was evaluated in a mouse model of CE. We found that Exos isolated from ADSCs could be taken up by HESCs. Exos elevated the proliferation and inhibited apoptosis in LPS-treated HESCs. Administration of Exos to HESCs suppressed the content of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Moreover, Exos exposure repressed the inflammation stimulated by LPS in vivo. Mechanistically, we demonstrated that Exos exerted their ant-inflammatory effect via miR-21/TLR4/NF-kB signaling pathway in endometrial cells. Our findings suggest that ADSC-Exo-based therapy might serve as an attractive strategy for the treatment of CE.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders, affecting the basal nuclei, causing impairment of motor and cognitive functions. Loss of dopaminergic (DAergic) neurons or their degeneration and the aggregation of Lewy bodies is the hallmark of this disease. The medications used to treat PD relieve the symptoms and maintain quality of life, but currently, there is no cure. There is a need for the development of therapies that can cease or perhaps reverse neurodegeneration effectively. With the rapid advancements in cell replacement therapy techniques, medical professionals are trying to find a cure by which restoration of dopamine neurotransmitters can occur. Researchers have started focusing on cell-based therapies using mesenchymal stem cells (MSCs) due to their abundance in the body, the ability of proliferation, and immunomodulation. Here we review the MSC-based treatment in Parkinson's disease and the various mechanisms it repairs DAergic neurons in parkinsonian patients.

Targeted therapies have significantly improved survival rates and quality of life for many cancer patients. However, on- and off-target side toxicities in normal tissues, and precocious activation of the immune response remain significant issues that limit the efficacy of molecular targeted agents. Extracellular vesicles (EVs) hold great promise as the mediators of next-generation therapeutic payloads. Derived from cellular membranes, EVs can be engineered to carry specific therapeutic agents in a targeted manner to tumor cells. This review highlights the progress in our understanding of basic EV biology, and discusses how EVs are being chemically and genetically modified for use in clinical and preclinical studies.

Major breakthroughs and disruptive methods in disease treatment today owe their thanks to our inch by inch developing conception of the infinitive aspects of medicine since the very beginning, among which, the role of the regenerative medicine can on no account be denied, a branch of medicine dedicated to either repairing or replacing the injured or diseased cells, organs, and tissues. A novel means to accomplish such a quest is what is being called "medical biowaste", a large assortment of biological samples produced during a surgery session or as a result of physiological conditions and biological activities. The current paper accentuating several of a number of promising sources of biowaste together with their plausible applications in routine clinical practices and the confronting challenges aims at inspiring research on the existing gap between clinical and basic science to further extend our knowledge and understanding concerning the potential applications of medical biowaste.

Subcision method is one of the main techniques for treatment of acne scars or stromal-vascular fraction (SVF) and combined therapy can improve treatment strategy.

To use subcision method along with SVF for treatment of acne scar and comprised with alone subcision method.

In this double-blind clinical trial study, 10 patients with acne scars were entered into the study. Subcision technique was randomly performed on one side of the face and subcision technique plus SVF on opposite side of the face. All patients were examined before treatment and after 3 months by Visioface for volume, area, and depth of scars, as well as thickness and density of the epidermis and dermis of the scars in question. In addition, doctor's and patients' satisfaction, tolerability, and safety were determined after 3 months of treatment. Finally, statistical analysis was done by SPPS, version 25.

In terms of volume and area of scars, the mean percent change was 46.55 ± 13.92 and 44.60 ± 5.76, for the case group, and 13.31 ± 9.27 and 11.28 ± 9.64 for the control group, respectively. So, combined therapy led to significant recovery compared with alone subcision method (p value < 0.001). In both interventions, the increase of density and thickness was proven after treatment, also a significant difference in complete, epidermal, and dermal thickness and epidermal density variables was observed between combined therapy and alone subcision (p value < 0.05). Mean score of doctor's and patients' satisfaction in combined therapy (7.10 ± 0.74 and 7.10 ± 0.99, respectively), was also significantly higher than subcision alone (5.50 ± 0.53 and 5.30 ± 1.25, respectively). Finally, no complications were observed in the patients.

According to the acquired results, combined therapy can be considered as effective and safe treatment for acne scars with significant higher efficacy compared with subcision alone.