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Differences between systemic and non-systemic homing mechanisms. Both systemic and non-systemic homing to the extracellular matrix and stem cells to their destination, MSCs secrete MMPs and remodel the extracellular matrix.
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Mesenchymal stem cells (MSCs) are considered a promising regenerative therapy due to their ability to migrate toward damaged tissues. The homing ability of MSCs is unique compared with that of non-migrating cells and MSCs are considered promising therapeutic vectors for targeting major cells in many pathophysiological sites. MSCs have many advantag...
Citations
... The homing property of UC-MSCs is the key to their direct participation in the repair of skin injury. Many animal experiments have confirmed that when there is injury in the body, transplanted UC-MSCs can migrate to the injured site, differentiate, and replace injured cells using the chemotaxis of the injured tissue microenvironment [47][48][49] . However, with the deepening of the research, the view that MSCs differentiate and replace injured cells is no longer supported. ...
Aging is the main cause of many degenerative diseases. The skin is the largest and the most intuitive organ that reflects the aging of the body. Under the interaction of endogenous and exogenous factors, there are cumulative changes in the structure, function, and appearance of the skin, which are characterized by decreased synthesis of collagen and elastin, increased wrinkles, relaxation, pigmentation, and other aging characteristics. skin aging is inevitable, but it can be delayed. The successful isolation of mesenchymal stromal cells (MSC) in 1991 has greatly promoted the progress of cell therapy in human diseases. The International Society for Cellular Therapy (ISCT) points out that the MSC is a kind of pluripotent progenitor cells that have self-renewal ability (limited) in vitro and the potential for mesenchymal cell differentiation. This review mainly introduces the role of perinatal umbilical cord-derived MSC(UC-MSC) in the field of skin rejuvenation. An in-depth and systematic understanding of the mechanism of UC-MSCs against skin aging is of great significance for the early realization of the clinical transformation of UC-MSCs. This paper summarized the characteristics of skin aging and summarized the mechanism of UC-MSCs in skin rejuvenation reported in recent years. In order to provide a reference for further research of UC-MSCs to delay skin aging.
... Adult stem cells, such as MSCs, exist in various tissues and have the potential for multidirectional differentiation. These types of stem cells are expected to be developed as useful cell carriers to achieve targeted drug delivery due to their natural inflammatory homing characteristics [38]. It is generally believed that the therapeutic effect of MSCs is closely related to their multi-directional differentiation potential and paracrine function. ...
Osteoporosis is a common degenerative bone disease. The treatment of osteoporosis remains a clinical challenge in light of the increasing aging population. Human dental pulp stem cells (DPSCs), a type of mesenchymal stem cells (MSCs), are easy to obtain and have a high proliferation ability, playing an important role in the treatment of osteoporosis. However, MSCs undergo apoptosis within a short time when used in vivo; therefore, apoptotic vesicles (apoVs) have attracted increasing attention. Currently, the osteogenic effect of DPSC-derived apoVs is unknown; therefore, this study aimed to determine the role of DPSC-derived apoVs and their potential mechanisms in bone regeneration. We found that MSCs could take up DPSC-derived apoVs, which then promoted MSC osteogenesis in vitro. Moreover, apoVs could increase the trabecular bone count and bone mineral density in the mouse osteoporosis model and could promote bone formation in rat cranial defects in vivo. Mechanistically, apoVs promoted MSC osteogenesis by activating the extracellular regulated kinase (ERK)1/2 signaling pathway. Consequently, we propose a novel therapy comprising DPSC-derived apoVs, representing a promising approach to treat bone loss and bone defects.
... These biomimetic nanocarriers have a "shell-core" structure, with different nanoparticles inside and a cell membrane on the outer layer [37,38]. Common cell membranes include the red blood cell membrane [39], platelet membrane [40], macrophage membrane [41], and stem cell membrane [42]. After stroke, peripheral macrophages are recruited to the central nervous system to participate in and regulate neuroinflammation. ...
Ischemic stroke is associated with a high mortality rate, and effective treatment strategies are currently lacking. In this study, we aimed to develop a novel nano delivery system to treat ischemic stroke via intranasal administration. A three-factor Box–Behnken experimental design was used to optimize the formulation of liposomes co-loaded with Panax notoginseng saponins (PNSs) and Ginsenoside Rg3 (Rg3) (Lip-Rg3/PNS). Macrophage membranes were coated onto the surface of the optimized liposomes to target the ischemic site of the brain. The double-loaded liposomes disguised by macrophage membranes (MM-Lip-Rg3/PNS) were spherical, in a “shell–core” structure, with encapsulation rates of 81.41% (PNS) and 93.81% (Rg3), and showed good stability. In vitro, MM-Lip-Rg3/PNS was taken up by brain endothelial cells via the clathrin-dependent endocytosis and micropinocytosis pathways. Network pharmacology experiments predicted that MM-Lip-Rg3/PNS could regulate multiple signaling pathways and treat ischemic stroke by reducing apoptosis and inflammatory responses. After 14 days of treatment with MM-Lip-Rg3/PNS, the survival rate, weight, and neurological score of middle cerebral artery occlusion (MCAO) rats significantly improved. The hematoxylin and eosin (H&E) and TUNEL staining results showed that MM-Lip-Rg3/PNS can reduce neuronal apoptosis and inflammatory cell infiltration and protect the ischemic brain. In vivo biological experiments have shown that free Rg3, PNS, and MM-Lip-Rg3/PNS can alleviate inflammation and apoptosis, especially MM-Lip-Rg3/PNS, indicating that biomimetic liposomes can improve the therapeutic effects of drugs. Overall, MM-Lip-Rg3/PNS is a potential biomimetic nano targeted formulation for ischemic stroke therapy.
... To eliminate these disadvantages, mimicking exosome-like synthetic structures or using exosomes and these structures as hybrids provides new therapeutic advantages. [66,67] ...
Extracellular vesicles (EVs) are particles released by almost all types of cells into the extracellular space and are delimited by a lipid bilayer membrane, but they cannot duplicate themselves like cells. They can be divided into three subtypes: microvesicles, apoptotic bodies, and exosomes, according to their size, synthesis mechanism, and origin. Although the size of EVs varies between 50 to 1000 nm, exosomes are the smallest vesicles derived from the endosomal pathway and are typically 30-150 nm in size. Exosomes can be derived from various sources, such as dendritic cells and mesenchymal stem cells (MSCs). Among these sources, MSCs are the most convenient and efficient sources since they are biocompatible and offer potential as a therapeutic agent. Mesenchymal stem cell-derived exosomes contain a variety of biomolecules, including proteins, lipids, and carbohydrates, as well as nucleic acids such as deoxyribonucleic acid and micro-ribonucleic acid that have significant functions in transferring genetic material between cells. The MSCs-derived exosomes have emerged as an area of intense research interest in recent years due to their potential applications in various fields such as regenerative medicine, immunotherapy, and drug delivery. In this review, we not only emphasize exosomes and their biological functions but also examine MSC-derived exosomes and their obtaining methods in detail, as well as the current state of knowledge and research on their therapeutic strategies. Furthermore, we discuss new methodologies concerning the challenges of applying exosomes in healthcare and emphasize future perspectives to present effective and safe insights for exosome studies.
... Among the various inhibitors, latrunculin A (LatA) and cytochalasin D (CytD), both actin-depolymerizing reagents, significantly reduced the number of microvilli (Fig. 7a). Interestingly, this result is consistent with the previous reports demonstrating that actindisrupting agents can rapidly release the coated vesicles from the plasma membrane 25,26 . ...
Although T cell activation is known to involve the internalization of the T cell antigen receptor (TCR), much less is known regarding the release of TCRs following T cell interaction with cognate antigen-presenting cells. In this study, we examine the physiological mechanisms underlying TCR release following T cell activation. We show that T cell activation results in the shedding of TCRs in T cell microvilli, which involves a combined process of trogocytosis and enzymatic vesiculation, leading to the loss of membrane TCRs and microvilli-associated proteins and lipids. Surprisingly, unlike TCR internalization, this event results in the rapid upregulation of surface TCR expression and metabolic reprogramming of cholesterol and fatty acid synthesis to support cell division and survival. These results demonstrate that TCRs are lost through trogocytic ‘molting’ following T cell activation and highlight this mechanism as an important regulator of clonal expansion.
... Simultaneously, MSCs possess a natural tropism for inflamed or diseased tissues and can be used as vehicles to transport NPs loaded with drugs to these sites [32]. In addition, MSCs can also help protect AuNPs from clearance by the immune system, thereby enhancing their therapeutic efficacy [33]. In this study, we aimed to evaluate improvements in biological performance achieved by appropriate concentrations of AuNPs via the SDF-1/CXCR4 signaling pathway, which can influence MSC migration and proliferation. ...
In the present study, the various concentrations of AuNP (1.25, 2.5, 5, 10 ppm) were prepared to investigate the biocompatibility, biological performances and cell uptake efficiency via Wharton’s jelly mesenchymal stem cells and rat model. The pure AuNP, AuNP combined with Col (AuNP-Col) and FITC conjugated AuNP-Col (AuNP-Col-FITC) were characterized by Ultraviolet–visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR) and Dynamic Light Scattering (DLS) assays. For in vitro examinations, we explored whether the Wharton’s jelly MSCs had better viability, higher CXCR4 expression, greater migration distance and lower apoptotic-related proteins expression with AuNP 1.25 and 2.5 ppm treatments. Furthermore, we considered whether the treatments of 1.25 and 2.5 ppm AuNP could induce the CXCR4 knocked down Wharton’s jelly MSCs to express CXCR4 and reduce the expression level of apoptotic proteins. We also treated the Wharton’s jelly MSCs with AuNP-Col to investigate the intracellular uptake mechanisms. The evidence demonstrated the cells uptake AuNP-Col through clathrin-mediated endocytosis and the vacuolar-type H+-ATPase pathway with good stability inside the cells to avoid lysosomal degradation as well as better uptake efficiency. Additionally, the results from in vivo examinations elucidated the 2.5 ppm of AuNP attenuated foreign body responses and had better retention efficacy with tissue integrity in animal model. In conclusion, the evidence demonstrates that AuNP shows promise as a biosafe nanodrug delivery system for development of regenerative medicine coupled with Wharton’s jelly MSCs.
... Membrane fusion liposomes have the advantages of good stability, long circulation half-life and low immunogenicity. Liposomes have an exact replica of the targeting properties of membrane vesicles [124]. ...
Liposomes, the most widely studied nano-drug carriers in drug delivery, are sphere-shaped vesicles consisting of one or more phospholipid bilayers. Compared with traditional drug delivery systems, liposomes exhibit prominent properties that include targeted delivery, high biocompatibility, biodegradability, easy functionalization, low toxicity, improvements in the sustained release of the drug it carries and improved therapeutic indices. In the wake of the rapid development of nanotechnology, the studies of liposome composition have become increasingly extensive. The molecular diversity of liposome composition, which includes long-circulating PEGylated liposomes, ligand-functionalized liposomes, stimuli-responsive liposomes, and advanced cell membrane-coated biomimetic nanocarriers, endows their drug delivery with unique physiological functions. This review describes the composition, types and preparation methods of liposomes, and discusses their targeting strategies in cancer therapy.
... They show great potential in tumor imaging diagnosis, nucleic acid delivery, drug delivery, vaccination, atherosclerosis treatment, rheumatoid arthritis treatment, nervous system disease treatment, and chemotherapy. 21,[79][80][81][82][83][84][85][86] To achieve therapeutic effects, NPs must remain persistent in the blood, avoid being cleared by MPS and reticuloendothelial system (RES), cross the biological barrier, accumulate at the injured area, and interact with the target cells. ...
Acute myocardial infarction (MI) remains a serious disease causing lots of death and disability worldwide. Early and effective application of thrombolytic therapy or primary percutaneous coronary intervention (PCI) for myocardial reperfusion can reduce the size of MI. However, the process of recovering blood flow to the ischemic myocardium can lead to myocardial cell death, known as myocardial reperfusion injury. Due largely to the lack of therapeutic targeting and the complexity of cytokine interactions, there is still no effective treatment to protect the heart from myocardial ischemia/reperfusion injury (MIRI). Nanomedicine has always been at the forefront of medicine. However, nanoparticles (NPs) possess several limitations, such as poor targeting, biological stability, and ease of clearance by the immune system in vivo. Therefore, a method of immune cell membrane-coated NPs is proposed to solve these problems. Recently, the targeted treatment of diseases by cell membrane-encapsulated drugs has received increasing attention. The technical progress of immune cell membrane-coated NPs can realize the benefits of high targeting, high specificity, and low side effects on lesions and has great potential for treating MIRI. Herein, cell-derived membrane-coated nanosystems, their preparation process, and the applicability of these biomimetic systems in reducing MIRI injury are discussed. Finally, the prospects and challenges for their clinical translation are also introduced.
... Mesenchymal stem cells mimicking nanoencapsulations encapsulate pharmaceuticals with a variety of components, such as chemotherapeutic agents, nucleic acids, and proteins [74], and MSCs mimicking nanoencapsulation employ the cell membrane fraction as the capsule and targeting molecules, such as chemokine receptors [75,76]. The capacity of MSCs to be loaded with infliximab to be released at the site of nephrotic inflammation makes it a superior choice among drug delivery systems. ...
Background and aim:
A delivery system consisting of bone marrow mesenchymal stem cells (MSCs) loaded with polyethylene glycol (PEG) coated superparamagnetic iron oxide nanoparticles (SPIONs) was constructed to treat a rat model of cisplatin (Cis)-induced nephrotoxicity with 1/10 of the common dose of anti-tumor necrosis factor-alpha (TNF-α) antibodies (infliximab).
Materials and methods:
Morphology, size, crystallinity, molecular structure, and magnetic properties of uncoated and PEG-coated SPIONs were analyzed. A delivery system consisting of MSCs containing infliximab-labeled PEG-coated SPIONs (Infliximab-PEG-SPIONs-MSCs) was generated and optimized before treatment. Fifty female Wistar rats were divided into five equal groups: Group 1: Untreated control; Group 2 (Cis): Rats were administered Cis through intraperitoneal (i.p.) injection (8 mg/kg) once a week for 4 weeks; Group 3 (Infliximab): Rats were injected once with infliximab (5 mg/kg), i.p. 3 days before Cis administration; Group 4 (Cis + MSCs): Rats were injected with Cis followed by an injection of 2 × 106 MSCs into the tail vein twice at a 1-week interval; and Group 5 (Cis + Infliximab (500 mg/kg)-PEG-SPIONs-MSCs): Rats were injected with the delivery system into the tail vein twice at a 1-week interval. Besides histological examination of the kidney, the Doppler ultrasound scanner was used to scan the kidney with the Gray-color-spectral mode.
Results:
In vivo, intra-renal iron uptake indicates the traffic of the delivery system from venous blood to renal tissues. Cis-induced nephrotoxicity resulted in a significant increase in TNF-α and malondialdehyde (MDA) (p < 0.05), bilirubin, creatinine, and uric acid (p < 0.01) levels compared with the untreated control group. The different treatments used in this study resulted in the amelioration of some renal parameters. However, TNF-α levels significantly decreased in Cis + Infliximab and Cis + MSCs (p < 0.05) groups. The serum levels of MDA significantly decreased in Cis + Infliximab (p < 0.05), Cis + MSCs (p < 0.05), and Cis + Infliximab-PEG-SPIONs-MSCs (p < 0.01). Furthermore, the serum activities of antioxidant enzymes were significantly elevated in the Cis + MSCs and Cis + Infliximab-PEG-SPIONs-MSCs groups (p < 0.05) compared to the Cis-induced nephrotoxicity rat model.
Conclusion:
With the support of the constructed MSCs-SPIONs infliximab delivery system, it will be possible to track and monitor cell homing after therapeutic application. This infliximab-loading system may help overcome some challenges regarding drug delivery to the target organ, optimize therapeutics' efficacy, and reduce the dose. The outcomes of the current study provide a better understanding of the potential of combining MSCs and antibodies-linked nanoparticles for the treatment of nephrotoxicity. However, further investigation is recommended using different types of other drugs. For new approaches development, we should evaluate whether existing toxicity analysis and risk evaluation strategies are reliable and enough for the variety and complexity of nanoparticles.
... In this review, we aimed to investigate the stem cell membranecamouflaged targeted delivery system in tumors. Two previous studies mainly focus on the roles of the MSC membrane in the diseases of inflammation [16] and arthritis [17]. To thoroughly reveal the stem cell membrane-based delivery system in tumors, we first discussed the underlying mechanisms of stem cell homing to target tumor tissues. ...
Cell membrane-coated nanoparticles (NPs) have attracted growing attention in the field of targeted delivery strategies, which successfully combine the advantages and properties of both cell membranes and synthetic NPs. Stem cell-based delivery systems have the innate targeting capability to tumor tissues, but inappropriate stem cells might promote tumor growth after being injected into the body. Accordingly, it is urgent to explore novel drug delivery systems that might combine the advantages of stem cells and eliminate the possible risks. This review aimed to investigate the stem cell membrane-camouflaged targeted delivery system in tumors. We discussed the underlying mechanisms of stem cell homing to target tumors. Then, the common membrane modification methods well as preparation methods of stem cell membrane coated NPs were concluded. NPs coating the stem cell membranes could obtain the tumor targeting ability, enhanced biocompatibility, and effective drug loading. Furthermore, we investigated the potential clinical applications of mesenchymal stem cells (MSCs) and induced pluripotent stem (iPS) cells membrane-camouflaged targeted delivery systems for anti-tumor therapies, such as chemotherapy, photodynamic therapy, magnetic hyperthermia therapy and imaging, CRISPR-Cas9 gene therapy, and synergistic therapy. Taken together, stem cell membrane-coated NPs hold the tremendous prospect for biomedical applications in tumor therapy.
