The cross talk between type II diabetic microenvironment and the regenerative capacities of human adipose tissue-derived pericytes: a promising cell therapy.

BACKGROUND: Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells (ECs) to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs. METHODS: PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients. The functionality of PCs was analyzed after 6, 14, and 30 days. RESULTS: Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin-related protein 2/3 complex, and downregulated COL21A1 protein expression. These cells suffered more pronounced apoptosis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein, serine/threonine protein phosphatase, and caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 TERF2, and upregulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. Further, DS-treated cells also showed disruption in the expression of the focal adhesion and binding proteins TSP1, TGF-ß, fibronectin, and PCDH7. Interestingly, DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maintaining the intracellular reactive oxygen species (ROS) level and upregulation of extracellular matrix (ECM) organizing proteins as vinculin, IQGAP1, and tubulin beta chain. CONCLUSION: These data showed that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of T2DM. Nevertheless, PCs have shown remarkable protective mechanisms when initially exposed to DS and thus they could provide a promising cellular therapy for T2DM.

Accelerating wound healing: Unveiling synergistic effects of P25/SWCNT/Ag and P25/rGO/Ag nanocomposites within PRP-gelatin scaffold, highlighting the synergistic antimicrobial activity.

Wound healing is a multifaceted biological process requiring innovative strategies to enhance efficiency and counter infections. In this groundbreaking study, we investigate the regenerative potential of platelet-rich plasma (PRP) integrated into a gelatin (GLT) scaffold along with nanocomposites of titanium dioxide (TiO2) (P25)/single-walled carbon nanotubes (SWCNTs)/Ag and P25/reduced graphene oxide (rGO)/Ag. Incorporating these advanced materials into the PRP/GLT delivery system aims to optimize the controlled release of growth factors (GFs) and leverage the exceptional properties of nanomaterials for enhanced tissue repair and wound healing outcomes. Antioxidant activity assessment using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity reveals the superior performance of P25/SWCNTs/Ag compared to P25/rGO/Ag. Their synergistic effects are evaluated in conjunction with antibacterial and antifungal antibiotics. Furthermore, the wound healing potential of P25/SWCNTs/Ag and P25/rGO/Ag, combined with PRP/GLT, is examined. Notably, both nanocomposites exhibit promising synergistic effects with gentamicin and fluconazole against pathogenic strains. Significantly, the inclusion of non-activated PRP substantially augments the wound healing efficacy of P25/SWCNTs/Ag on days 3 (p < 0.01) and 15 (p < 0.05). These findings pave the way for advanced wound dressing and therapeutic interventions, capitalizing on the synergistic effects of PRP and nanomaterials, thus ultimately benefiting patients and advancing regenerative medicine.

Curcumin-infused nanostructured lipid carriers: a promising strategy for enhancing skin regeneration and combating microbial infection.

BACKGROUND: Curcumin is a biomolecule that can be extracted from the Curcuma longa that has been shown to have the potential to aid skin wound healing. It has been studied for its anti-inflammatory and antioxidant properties, which may help to reduce swelling and promote tissue repair. However, curcumin has low solubility in water, which can limit its absorption and bioavailability. Encapsulating it in lipid nanoparticles may help to increase its absorption, leading to improved bioavailability. METHODS: Curcumin-loaded nanostructure lipid nanocarriers (CURC-NLCs) were prepared and characterized. Also, the phenolic, flavonoid contents, antioxidant and antimicrobial efficacy against gram-positive and gram-negative bacteria were investigated. Furthermore, in vivo rabbit animal model was used to test its regenerative capacity and wound-healing efficiency. RESULTS: The CURC-NLCs significantly increased the content of phenolic and flavonoid compounds compared to curcumin, resulting in a dramatic increase in antioxidant activity. CURC-NLCs also showed a potent inhibitory effect on Gram-positive, Gram-negative, and fungi, two times higher than curcumin. CURC-NLCs showed a higher potential to fasten the wound healing of full-thickness skin injuries as it resulted in 1.15- and 1.9-fold higher wound closure at the first week of injury compared to curcumin and control, respectively (p < 0.0001). CONCLUSION: These results suggest that CURC-NLCs have an excellent potential to promote skin regeneration, which could be attributed to its antioxidant and broad-spectrum antimicrobial effect.

Ternary nanocomposite potentiates the lysophosphatidic acid effect on human osteoblast (MG63) maturation.

Aim: This study aimed to investigate the potential of ternary nanocomposite (TNC) to support MG63 osteoblast maturation to EB1089-(3S)1-fluoro-3-hydroxy-4-(oleoyloxy)butyl-1-phosphonate (FHBP) cotreatment. Materials & methods: Binary (P25/reduced graphene oxide [rGO]) nanocomposite was prepared, and silver (Ag) nanoparticles were loaded onto the surface to form TNC (P25/rGO/Ag). The influence of TNC on proliferation, alkaline phosphatase activity and osteogenic gene expression was evaluated in a model of osteoblast maturation wherein MG63 were costimulated with EB1089 and FHBP. Results: TNC had no cytotoxic effect on MG63. The addition of TNC to EB1089-FHBP cotreatment enhanced the maturation of MG63, as supported by the greater alkaline phosphatase activity and OPN and OCN gene expression. Conclusion: TNC could serve as a promising carrier for FHBP, opening up possibilities for its application in bone regeneration.

Nanoparticles (NPs) are often used in medicine because they have certain benefits over traditional drugs, such as increased delivery. Multiple NPs can be combined into hybrid NPs called nanocomplexes, which can have many positive effects. One application of nanomedicine is to encourage the repair of certain body tissues such as bones. Encouraging stem cells to differentiate into bone cells and immature bone cells to mature is key in this process. This study made a ternary nanocomplex (TNC), meaning it was comprised of three NPs. This TNC was designed to deliver a drug called (3S)1-fluoro-3-hydroxy-4-(oleoyloxy)butyl-1-phosphonate (FHBP), which has been shown to encourage the maturation and development of osteoblasts, a type of bone cell. The TNC was made up of silver NPs, which can kill bacteria; reduced graphene oxide, which enhances the production of bone cells; and titanium dioxide, which has shown effectiveness in wound healing and mixed results in bone tissue regeneration. This TNC was tested on a cell line that comes from a type of bone cancer called MG63. The TNC was found to not be toxic to these cells. TNC incorporation into FHBP treatment enhanced the maturation of MG63. This suggests that these TNCs could be an effective treatment to encourage bone repair following joint replacement surgeries.

The interplay of cells, polymers, and vascularization in three-dimensional lung models and their applications in COVID-19 research and therapy.

Millions of people have been affected ever since the emergence of the corona virus disease of 2019 (COVID-19) outbreak, leading to an urgent need for antiviral drug and vaccine development. Current experimentation on traditional two-dimensional culture (2D) fails to accurately mimic the in vivo microenvironment for the disease, while in vivo animal model testing does not faithfully replicate human COVID-19 infection. Human-based three-dimensional (3D) cell culture models such as spheroids, organoids, and organ-on-a-chip present a promising solution to these challenges. In this report, we review the recent 3D in vitro lung models used in COVID-19 infection and drug screening studies and highlight the most common types of natural and synthetic polymers used to generate 3D lung models.

A pilot study to demonstrate the paracrine effect of equine, adult allogenic mesenchymal stem cells in vitro, with a potential for healing of experimentally-created, equine thoracic wounds in vivo.

Regenerative biological therapies using mesenchymal stem cells (MSCs) are being studied and used extensively in equine veterinary medicine. One of the important properties of MSCs is the cells' reparative effect, which is brought about by paracrine signaling, which results in the release of biologically active molecules, which in turn, can affect cellular migration and proliferation, thus a huge potential in wound healing. The objective of the current study was to demonstrate the in vitro and in vivo potentials of equine allogenic bone marrow-derived MSCs for wound healing. Equine bone marrow-derived MSCs from one allogenic donor horse were used. Equine MSCs were previously characterized for their in vitro proliferation, expression of cluster-of-differentiation markers, and trilineage differentiation. MSCs were first evaluated for their migration using an in vitro wound healing scratch assay, and subsequently, the conditioned medium was evaluated for their effect on human fibroblast proliferation. Subsequently, allogenic cells were intradermally injected into full-thickness, cutaneous thoracic wounds of 4 horses. Wound healing was assessed by using 3-D digital imaging and by measuring mRNA expression of pro-and anti-inflammatory markers for 30 days. Using human fibroblasts in an in vitro wound healing assay, we demonstrate a significantly higher healing in the presence of conditioned medium collected from proliferating MSCs than in the presence of medium containing fetal bovine serum. The in vitro effect of MSCs did not translate into a detectable effect in vivo. Nonetheless, we proved that molecularly characterized equine allogenic MSCs do not illicit an immunologic response. Investigations using MSCs derived from other sources (adipose tissue, umbilical cord), or a higher number of MSCs or a compromised animal model may be required to prove the efficacy of equine MSCs in wound healing in vivo.

Comparative evaluation of propolis nanostructured lipid carriers and its crude extract for antioxidants, antimicrobial activity, and skin regeneration potential.

BACKGROUND: Propolis extracted from beehives has been conferred with natural antimicrobial and antioxidant properties. Hence, it has been recommended as a wound healing therapy. This study investigated the additive value of nanotechnology to the herbal extract, (propolis rebuts), after which we examined its efficacy in wound healing. METHODS: Propolis nanostructured lipid carriers (NLCs) were first prepared using the emulsion-evaporation-solidification method at three concentrations. Then, we compared their flavonoid and phenolic contents and phenolic contents. Their antioxidant, antibacterial, and antifungal effects were also investigated after which, the skin regenerative capacity of propolis-NLCs was assessed using full-thickness skin wounds in rabbits. RESULTS: This study showed that propolis-NLCs had increased the phenolic and flavonoid contents compared to the raw propolis extract (EXTR) (9-fold and 2-fold, respectively). This increase was reflected in their antioxidant activities, which dramatically increased by 25-fold higher than the propolis-EXTR. Also, propolis-NLCs exhibited a 2-fold higher potent inhibitory effect than propolis-EXTR on Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), Gram-negative bacterium (Salmonella spp.), and fungus (Candida albicans) microbes (p < 0.0001). Investigations also revealed that treatment of full-thickness skin injuries with propolis-NLCs resulted in significantly higher wound closure compared to propolis-EXTR and the control after two weeks (p < 0.0001). CONCLUSION: With a prominent broad-spectrum antibacterial effect propolis-NLCs exhibited higher skin regenerative potency than propolis-EXTR. We also highlighted the additive impact of nanotechnology on herbal extract, which accounted for the increased flavonoid content and hence a better antioxidant and antimicrobial effect and propose it as a potential therapy for wound healing.

Applications of the amniotic membrane in tissue engineering and regeneration: the hundred-year challenge.

The amniotic membrane (Amnio-M) has various applications in regenerative medicine. It acts as a highly biocompatible natural scaffold and as a source of several types of stem cells and potent growth factors. It also serves as an effective nano-reservoir for drug delivery, thanks to its high entrapment properties. Over the past century, the use of the Amnio-M in the clinic has evolved from a simple sheet for topical applications for skin and corneal repair into more advanced forms, such as micronized dehydrated membrane, amniotic cytokine extract, and solubilized powder injections to regenerate muscles, cartilage, and tendons. This review highlights the development of the Amnio-M over the years and the implication of new and emerging nanotechnology to support expanding its use for tissue engineering and clinical applications.

A Hyaluronic Acid Demilune Scaffold and Polypyrrole-Coated Fibers Carrying Embedded Human Neural Precursor Cells and Curcumin for Surface Capping of Spinal Cord Injuries.

Tissue engineering, including cell transplantation and the application of biomaterials and bioactive molecules, represents a promising approach for regeneration following spinal cord injury (SCI). We designed a combinatorial tissue-engineered approach for the minimally invasive treatment of SCI-a hyaluronic acid (HA)-based scaffold containing polypyrrole-coated fibers (PPY) combined with the RAD16-I self-assembling peptide hydrogel (Corning® PuraMatrix™ peptide hydrogel (PM)), human induced neural progenitor cells (iNPCs), and a nanoconjugated form of curcumin (CURC). In vitro cultures demonstrated that PM preserves iNPC viability and the addition of CURC reduces apoptosis and enhances the outgrowth of Nestin-positive neurites from iNPCs, compared to non-embedded iNPCs. The treatment of spinal cord organotypic cultures also demonstrated that CURC enhances cell migration and prompts a neuron-like morphology of embedded iNPCs implanted over the tissue slices. Following sub-acute SCI by traumatic contusion in rats, the implantation of PM-embedded iNPCs and CURC with PPY fibers supported a significant increase in neuro-preservation (as measured by greater ßIII-tubulin staining of neuronal fibers) and decrease in the injured area (as measured by the lack of GFAP staining). This combination therapy also restricted platelet-derived growth factor expression, indicating a reduction in fibrotic pericyte invasion. Overall, these findings support PM-embedded iNPCs with CURC placed within an HA demilune scaffold containing PPY fibers as a minimally invasive combination-based alternative to cell transplantation alone.

Human-Induced Neural and Mesenchymal Stem Cell Therapy Combined with a Curcumin Nanoconjugate as a Spinal Cord Injury Treatment.

We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesenchymal stem cells (MSC), and a pH-responsive polyacetal-curcumin nanoconjugate (PA-C) that allows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment protected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccharide-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of ß-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments.

Bone Marrow Mesenchymal Stem Cell-Derived Tissues are Mechanically Superior to Meniscus Cells.

Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to form the mechanically responsive matrices of joint tissues, including the menisci of the knee joint. The purpose of this study is to assess BMSC's potential to engineer meniscus-like tissue relative to meniscus fibrochondrocytes (MFCs). MFCs were isolated from castoffs of partial meniscectomy from nonosteoarthritic knees. BMSCs were developed from bone marrow aspirates of the iliac crest. All cells were of human origin. Cells were cultured in type I collagen scaffolds under normoxia (21% O2) for 2 weeks followed by hypoxia (3% O2) for 3 weeks. The structural and functional assessment of the generated meniscus constructs were based on glycosaminoglycan (GAG) content, histological appearance, gene expression, and mechanical properties. The tissues formed by both cell types were histologically positive for Safranin O stain and appeared more intense in the BMSC constructs. This observation was confirmed by a 2.7-fold higher GAG content. However, there was no significant difference in collagen I (COL1A2) expression in BMSC- and MFC-based constructs (p = 0.17). The expression of collagen II (COL2A1) and aggrecan (ACAN) were significantly higher in BMSCs than MFC (p ≤ 0.05). Also, the gene expression of the hypertrophic marker collagen X (COL10A1) was 199-fold higher in BMSCs than MFC (p < 0.001). Moreover, relaxation moduli were significantly higher in BMSC-based constructs at 10-20% strain step than MFC-based constructs. BMSC-based constructs expressed higher COL2A1, ACAN, COL10A1, contained higher GAG content, and exhibited higher relaxation moduli at 10-20% strain than MFC-based construct. Impact statement Cell-based tissue engineering (TE) has the potential to produce functional tissue replacements for irreparably damaged knee meniscus. But the source of cells for the fabrication of the tissue replacements is currently unknown and of research interest in orthopedic TE. In this study, we fabricated tissue-engineered constructs using type I collagen scaffolds and two candidate cell sources in meniscus TE. We compared the mechanical properties of the tissues formed from human meniscus fibrochondrocytes and bone marrow-derived mesenchymal stem cells (BMSCs). Our data show that the tissues engineered from the BMSC are mechanically superior in relaxation modulus.

Gelatin Loaded Titanium Dioxide and Silver Oxide Nanoparticles: Implication for Skin Tissue Regeneration.

Treatment of burn wounds has many requirements to ensure wound closure with healthy tissue, increased vascularization, guarantee edema resolution, and control bacterial infection. We propose that titanium oxide (TiO2) nanoparticles (NPs) will be more efficient than silver dioxide (Ag2O) in the treatment of burn wounds. Herein, gelatin loaded NPs (GLT-NPs) were evaluated for their efficacy to regenerate second-degree burn wound in rabbit skin. TEM results revealed that the average particle sizes were ⁓ 7.5 and 17 nm for Ag2O and TiO2 NPs, respectively. The results of the in vivo application of GLT-NPs on burn wound in the rabbit revealed that both Ag2O and TiO2 NPs were efficient than the control none treated (CTRL) and GLT group. In terms of the healing rate, the GLT-TiO2 did not show any significant difference than GLT-Ag2O (99.57% vs. 99.85%, p = 0.2). Meanwhile, the healing rate was significantly higher in both NPs' treated groups than CTRL (94.16%, p < 0.01) and GLT group (95.07%, p < 0.05). Also, the histological analysis using H&E staining showed re-epithelization, less edema, and enhanced vascularization in both GLT-NPs than CTRL and GLT groups. Furthermore, immunohistochemical analysis of TGF-ß1 and α-SMA revealed significantly a higher expression in both GLT-NPs groups than CTRL and GLT groups at weeks 1 and 2 (p < 0.05). Interestingly, TGF-ß1 and α-SMA were substantially higher in GLT- TiO2 than GLT-Ag2O at weeks 1 and 2 (p < 0.05), but the expression was not significant at week 3. In conclusion, GLT-NPs showed higher regenerative capacity and enhanced the healing quality after burn wound compared to CTRL and GLT. Graphical abstract.

Efficient tailoring of platinum nanoparticles supported on multiwalled carbon nanotubes for cancer therapy.

Aim: Therapeutically targeting cancer stem cells (CSCs), which play a role in tumor initiation and relapse, remains challenging. Materials & methods: Novel-formulated platinum nanoparticles (Pt-NPs) supported on polybenzimidazole (PBI)-functionalized polymers and multiwalled carbon nanotubes (MWCNT) were prepared and their effect on CSCs was evaluated. Results: Pt-NPs showed homogenous distribution on the surface of MWCNT/PBI composites, with very narrow particle size. MWCNT/PBI/Pt-NPs resulted in a dramatic decrease in the proliferation rate of CSCs but not bone marrow mesenchymal stem cells (BM-MSCs). Quantitative gene expression analysis revealed that MWCNT/PBI/Pt had a significant inhibitory effect on the epithelial-mesenchymal transition and cell cycle markers of CSCs. Conclusion: MWCNT/PBI/Pt exhibited a specific cytotoxic effect on breast CSCs but not on adult stem cells.

Stem Cell Therapy for Hepatocellular Carcinoma: Future Perspectives.

Hepatocellular carcinoma (HCC) is one of the most common types of cancer and results in a high mortality rate worldwide. Unfortunately, most cases of HCC are diagnosed in an advanced stage, resulting in a poor prognosis and ineffective treatment. HCC is often resistant to both radiotherapy and chemotherapy, resulting in a high recurrence rate. Although the use of stem cells is evolving into a potentially effective approach for the treatment of cancer, few studies on stem cell therapy in HCC have been published. The administration of stem cells from bone marrow, adipose tissue, the amnion, and the umbilical cord to experimental animal models of HCC has not yielded consistent responses. However, it is possible to induce the apoptosis of cancer cells, repress angiogenesis, and cause tumor regression by administration of genetically modified stem cells. New alternative approaches to cancer therapy, such as the use of stem cell derivatives, exosomes or stem cell extracts, have been proposed. In this review, we highlight these experimental approaches for the use of stem cells as a vehicle for local drug delivery.

Comparison of different uncoated and starch-coated superparamagnetic iron oxide nanoparticles: Implications for stem cell tracking.

However, labelling of stem cells using nanoparticles (NPs) for tracking purpose has been intensively investigated, the biosafety of these materials needs more clarification. Herein, different forms of iron oxide Fe2O3, Fe3O4, and CoxNi1-x Fe2O4 NPs either uncoated or starch-coated (ST-coated) were prepared. We successfully labelled adipose-derived stem cells (ASCs) using these NPs with the aid of lipofectamine as a transfection agent (TA). We then evaluated the effect of these NPs on stem cell proliferation, viability, migration and angiogenesis. Results showed that ASCs labelled with Fe2O3, Fe3O4, ST-Fe2O3 and ST-Fe3O4 did not show any significant difference in proliferation compared to that of TA-treated cells. Moreover, they have shown a protective effect against apoptosis. Conversely, CoxNi1-x Fe2O4 NPs caused a significant decrease in cell proliferation. Compared to that of the TA-treated cells, the migration capacity of cells labelled with Fe2O3, Fe3O4 and CoxNi1-xFe2O4 was significantly compromised. Interestingly, the ST-coated composites reversed this effect. Among the groups treated with different NPs, the angiogenic potential of the ASCs was most robust in the ST-Fe2O3-treated group. In conclusion, labelling ASCs with ST-Fe2O3 NPs enhanced cell migration and angiogenic potential and conferred higher resistance to apoptosis than labelling the cells with the other tested NPs.

Green propolis extract promotes in vitro proliferation, differentiation, and migration of bone marrow stromal cells.

BACKGROUND: Propolis is a resinous material extracted from bee glue with a complex chemical composition. The unique biological properties of propolis have led to its use in alternative medicine and as a nutritional supplement. Recent research shows that propolis could affect the immune system by decreasing the production of inflammatory cytokines and potentiating an effect on resident stem cells. The exact mechanism, however, is unknown. The goal of this study was to demonstrate whether green propolis extract affects any characteristic properties of mesenchymal stromal cells (MSCs)in vitro. METHODS: The cytocompatibility of propolis extract and the proliferation of bone marrow mesenchymal stromal cells (BMMSCs) in the presence of propolis was evaluated by live/dead cell staining and MTS viability assay over a period of 3 days. Also, we evaluated the effect of propolis extract on trilineage differentiation and migration capacity of undifferentiated and differentiated BMMSCs. RESULTS: Relative to the control, propolis extract resulted in a significant and linear increase in the proliferation of MSCs and inhibited the osteogenic differentiation of BMMSCs, while there was a potentiation of chondrogenesis and adipogenesis. Finally, in relevance to wound healing, an in vitro scratch assay demonstrated that the migratory potential of differentiated BMMSCs was enhanced in the presence of propolis. CONCLUSION: We have demonstrated that propolis extract was not toxic to BMMSCs (<400 µg/ml), supported their proliferation, potentiated chondrogenic and adipogenic differentiation processes, and supported cell migrationin vitro. Most interestingly, there was a down-regulation of osteogenesis. These data support the use of propolis extract for enhanced cell proliferation and tissue regeneration; however, it warrants further investigation.

Tissue regeneration: Impact of sleep on stem cell regenerative capacity.

The circadian rhythm orchestrates many cellular functions, such as cell division, cell migration, metabolism and numerous intracellular biological processes. The physiological changes during sleep are believed to promote a suitable microenvironment for stem cells to proliferate, migrate and differentiate. These effects are mediated either directly by circadian clock genes or indirectly via hormones and cytokines. Hormones, such as melatonin and cortisol, are secreted in response to neural optic signals and act in harmony to regulate many biological functions during sleep. Herein, we correlate the effects of the main circadian genes on the expression of certain stem cell genes responsible for the regeneration of different tissues, including bone, cartilage, skin, and intestine. We also review the effects of different hormones and cytokines on stem cell activation or suppression and their relationship to the day/night cycle. The correlation of circadian rhythm with tissue regeneration could have implications in understanding the biology of sleep and tissue regeneration and in enhancing the efficacy and timing of surgical procedures.

Telomerase reverse transcriptase coordinates with the epithelial-to-mesenchymal transition through a feedback loop to define properties of breast cancer stem cells.

Telomerase and its core component, telomerase reverse transcriptase (hTERT), are critical for stem cell compartment integrity. Normal adult stem cells have the longest telomeres in a given tissue, a property mediated by high hTERT expression and high telomerase enzymatic activity. In contrast, cancer stem cells (CSCs) have short telomeres despite high expression of hTERT, indicating that the role of hTERT in CSCs is not limited to telomere elongation and/or maintenance. The function of hTERT in CSCs remains poorly understood. Here, we knocked down hTERT expression in CSCs and observed a morphological shift to a more epithelial phenotype, suggesting a role for hTERT in the epithelial-to-mesenchymal transition (EMT) of CSCs. Therefore, in this study, we systematically explored the relationship between hTERT and EMT and identified a reciprocal, bi-directional feedback loop between hTERT and EMT in CSCs. We found that hTERT expression is mutually exclusive to the mesenchymal phenotype and that, reciprocally, loss of the mesenchymal phenotype represses hTERT expression. We also showed that hTERT plays a critical role in the expression of key CSC markers and nuclear ß-catenin localization, increases the percentage of cells with side-population properties, and upregulates the CD133 expression. hTERT also promotes chemoresistance properties, tumorsphere formation and other important functional CSC properties. Subsequently, hTERT knockdown leads to the loss of the above advantages, indicating a loss of CSC properties. Our findings suggest that targeting hTERT might improve CSCs elimination by transitioning them from the aggressive mesenchymal state to a more steady epithelial state, thereby preventing cancer progression.

Graphene nanoparticles as osteoinductive and osteoconductive platform for stem cell and bone regeneration.

The potential of graphene-based nanoparticles (GNPs) has recently gained significant attention in biomedicine, especially in tissue engineering. In this study, we investigated the osteoinductive and osteoconductive effects of low oxygen content graphene (LOG) nanoparticles on adult mesenchymal stem cells (MSCs) in vitro and in vivo. We showed that adult goat MSCs were viable in the presence of 0.1 mg/mL LOG and retained their stem cell properties. A 3D scaffold made from agarose was used to encapsulate MSCs and LOG nanoparticles. Scanning electron microscopy demonstrated the cell morphology and adherence of MSCs to LOG in the 3D form. The LOG and MSCs in the 3D scaffold were xenogenically implanted into a rat unicortical tibial bone defect. The combination of MSCs and LOG nanoparticles resulted in improved active bone formation and increased mineralization. These results strengthen the applicability of LOG nanoparticles as an adjunct treatment for bone tissue engineering.