Cells For Tissue Regeneration Research Articles

Functional diversity of apoptotic vesicle subpopulations from bone marrow mesenchymal stem cells in tissue regeneration.

Apoptosis releases numerous apoptotic vesicles that regulate processes such as cell proliferation, immunity, and tissue regeneration and repair. Now, it has also emerged as an attractive candidate for biotherapeutics. However, apoptotic vesicles encompass a diverse range of subtypes, and it remains unclear which specific subtypes play a pivotal role. In this study, we successfully isolated different apoptotic vesicle subtypes based on their sizes and characterized them using NTA and TEM techniques, respectively. We compared the functional variances among the distinct subtypes of apoptotic vesicles in terms of stem cell proliferation, migration, and differentiation, as well as for endothelial cell and macrophage function, effectively identifying subtypes that exhibit discernible functional differences. ApoSEV (with diameter<1000nm) promoted stem cell proliferation, migration, and multi-potent differentiation, and accelerated skin wound healing of diabetes mouse model, while apoBD (with diameter>1000nm) played the opposite effect on cell function and tissue regeneration. Lastly, employing protein analysis and gene sequencing techniques, we elucidated the intrinsic mechanisms underlying these differences between different subtypes of apoEVs. Collectively, this study identified that apoptotic vesicle subtypes possessed distinct bio-functions in regulating stem cell function and behaviour and modulating tissue regeneration, which primarily attribute to the distinct profiling of protein and mRNA in different subtypes. This comprehensive analysis of specific subtypes of apoEVs would provide novel insights for potential therapeutic applications in cell biology and tissue regeneration.

Stem cells and diabetes: Compassionate care with comfort, a humanized reflection

The aim was to analyze the role of stem cells in Diabetes Mellitus, adopting the humanized perspective of Kolcaba's Comfort Theory. The methodology used a reflexive approach, reviewing literature on platforms such as Google Scholar and PubMed. The results highlighted the capacity of stem cells in tissue regeneration in DM1, offering a promising vision. The scientific evidence revealed the versatility of stem cells, not only in insulin replacement, but also in differentiation into various cell lineages, broadening the therapeutic spectrum. The discussion addressed challenges including heterogeneity in individual responses, optimization of cell differentiation and ethical issues. The Comfort Theory enriched the analysis by highlighting the importance of compassionate care, promoting humanized practices and considering emotional dimensions. In stem cell transplantation, attention to the patient's emotional well-being, psychological support and effective communication were crucial. Methodological limitations were acknowledged, suggesting more in-depth approaches in future research, and practical implications were highlighted, proposing the integration of Comfort Theory into the therapeutic approach to optimize care for patients with Diabetes Mellitus.

Modulation of macrophages by a phillyrin-loaded thermosensitive hydrogel promotes skin wound healing in mice

BackgroundImpaired wound healing in traumatic skin injuries remains a severe clinical challenge due to impaired re-vascularization, harmful bacteria infection, and inflammation dysregulation. Macrophages are recognized as prominent immune cells in tissue regeneration and wound healing. Consequently, the modulation of macrophages provides a promising therapeutic target for wound healing disorders. Here, we aimed to explore whether a novel constructed combination of thermosensitive hydrogel Pluronic F-127 (PF-127) and phillyrin (PH, the main active compound of forsythia suspensa) could improve skin wound healing. MethodsFirstly, the biological effects of pH on the phenotype and inflammation of macrophages were assessed by flow cytometry and ELISA. The biocompatibility of the PF-127 plus PH combination was investigated on keratinocytes and red blood cells. The biological effect of PF-127/PH hydrogel on the migratory ability of keratinocytes in vitro was evaluated using the scratch and transwell migration assays. In addition,S. aureusandE. coliwere employed to test the antibacterial properties of the PF-127 plus PH combination. Finally, PF-127 plus PH scaffold was appliedto the full-thickness skin defect in mice. Histomorphological evaluation and immunochemistry were performed to explore the wound-healing activity of PF-127/PH hydrogel. ResultsPH can promote the polarization of macrophages from the M1 (pro-inflammatory) phenotype to the M2 (anti-inflammatory) phenotype. The PF-127/PH hydrogel was highly biocompatible and showed a potent stimulative effect on the migration of keratinocytesin vitro. The combination of PF-127 and PH exerted a pronounced antibacterial activity onS. aureusandE. coli in vitro.PF-127/PH hydrogel potently accelerates the healing of full-thickness skin defects by promoting skin cell proliferation, accelerating angiogenesis, and inhibiting inflammation. ConclusionsOur study suggests that PF-127/PH hydrogel has excellent potential for treating traumatic skin defects.

Coral Tissue Regeneration and Growth Is Associated with the Presence of Stem-like Cells

Members of the Cnidaria phylum were studied for centuries to depict the source of their unprecedented regeneration capacity. Although adult stem cells (ASCs) have been recognized in tissue growth/regeneration in many hydrozoans, there has not been any evidence of them in the ancestral Anthozoa class. This study sheds light on the development of epidermal epithelium expansion, akin to blastema, during tissue regeneration after small circular incisions (each 2.77 mm2) and during the natural expansion of tissue across a flat surface in the scleractinian coral Stylophora pistillata. Regeneration was completed within 9 days in 84.5% (n = 64) of the assays. About 35% of the samples regrew a single polyp, 60% showed no polyp regrowth, and approximately 6% exhibited multiple new polyps. We further used histological staining, pH3, Piwi immuno-histochemistry, and qPCR for eight stemness markers: Piwi-1, Nanos-1, Nanos-1-like, Tudor-5, Tudor-7, Boule, Sox-2, and Myc-1. The results revealed the formation of an “addendum”, an epidermal epithelium in the growing edges (in regenerating and normal-growing fronts) inhabited by a cluster of small cells featuring dense nuclei, resembling ASCs, many expressing pH3 as well as Piwi proteins. Most of the stemness genes tested were upregulated. These results indicate the participation of ASCs-like cells in tissue regeneration and growth in scleractinian corals.

Distinctive role of inflammation in tissue repair and regeneration.

Inflammation is an essential host defense mechanism in response to microbial infection and tissue injury. In addition to its well-established role in infection, inflammation is actively involved in the repair of damaged tissues and restoration of homeostatic conditions after tissue injury. The intensity of the inflammatory response and types of cells involved in inflammation have a significant impact on the quality of tissue repair. Numerous immune cell subtypes participate in tissue repair and regeneration. In particular, immune cell-derived secretants, including cytokines and growth factors, can actively modulate the proliferation of resident stem cells or progenitor cells to facilitate tissue regeneration. These findings highlight the importance of inflammation during tissue repair and regeneration; however, the precise role of immune cells in tissue regeneration remains unclear. In this review, we summarize the current knowledge on the contribution of specific immune cell types to tissue repair and regeneration. We also discuss how inflammation affects the final outcome of tissue regeneration.

Keratin-mediated hair growth and its underlying biological mechanism

Here we show that intradermal injection of keratin promotes hair growth in mice, which results from extracellular interaction of keratin with hair forming cells. Extracellular application of keratin induces condensation of dermal papilla cells and the generation of a P-cadherin-expressing cell population (hair germ) from outer root sheath cells via keratin-mediated microenvironmental changes. Exogenous keratin-mediated hair growth is reflected by the finding that keratin exposure from transforming growth factor beta 2 (TGFβ2)-induced apoptotic outer root sheath cells appears to be critical for dermal papilla cell condensation and P-cadherin-expressing hair germ formation. Immunodepletion or downregulation of keratin released from or expressed in TGFβ2-induced apoptotic outer root sheath cells negatively influences dermal papilla cell condensation and hair germ formation. Our pilot study provides an evidence on initiating hair regeneration and insight into the biological function of keratin exposed from apoptotic epithelial cells in tissue regeneration and development.

Extracellular Vesicles in Tissue Engineering: Biology and Engineered Strategy.

Extracellular vesicles (EVs), acting as an important ingredient of intercellular communication through paracrine actions, have gained tremendous attention in the field of tissue engineering (TE). Moreover, these nanosized extracellular particles (30-140nm) can be incorporated into biomaterials according to different principles to facilitate signal delivery in various regenerative processes directly or indirectly. Bioactive biomaterials as the carrier will extend the retention time and realize the controlled release of EVs, which further enhance their therapeutic efficiency in tissue regeneration. Herein, the basic biological characteristics of EVs are first introduced, and then their outstanding performance in exerting direct impacts on target cells in tissue regeneration as well as indirect effects on promoting angiogenesis and regulating the immune environment, due to specific functional components of EVs (nucleic acid, protein, lipid, etc.), is emphasized. Furthermore, different design ideas for suitable EV-loaded biomaterials are also demonstrated. In the end, this review also highlights the engineered strategies, which aim at solving the problems related to natural EVs such as highly heterogeneous functions, inadequate tissue targeting capabilities, insufficient yield and scalability, etc., thus promoting the therapeutic pertinence and clinical potential of EV-based approaches in TE.

A cell penetrating peptide-modified magnetic/fluorescent probe for in vivo tracking of mesenchymal stem cells.

Difficulty in precise tracking of the in vivo distribution and migration of transplanted stem cells in a noninvasive way is a great hurdle in regenerative medicine research. Paramagnetic element-doped upconversion nanoparticles (UCNPs) emerge as a kind of promising dual-modal imaging agents owing to the possibility in combining strong contrast of MR imaging and high efficiency of fluorescence imaging. Herein a kind of Mn-doped NaYF4-based UCNPs (NaYF4: 20%Yb, 2%Er, 30%Mn) was developed and then hydrophilized by various coatings, including cell penetrating peptide, DNA, and SiO2 . The UCNPs were denoted as Pep/UCNPs, DNA/UCNPs, and SiO2 /UCNPs, respectively. Their potential in cell labeling and in vivo tracking applications was comprehensively explored. The results show that the Mn-doped UCNPs possess high biocompatibility, high cell labeling efficiency, high MR resolution, and importantly a single emission at 660 nm, within optical window for in vivo imaging of biological targets. Particularly, mesenchymal stem cells (MSCs) pre-labeled by cell penetrating peptide-modified UCNPs (Pep/UCNPs) can be precisely monitored in terms of their distribution in mice over a long period of time by simultaneous MR and fluorescent imaging, which provided a noninvasive and double-checking tool for investigating the destination of stem cells in tissue regeneration.

Usage of platelet-rich fibrin (PRF) membranes for closure of soft palate recurrent fistula

Introduction: Palatal fistula is a relatively common complication of surgical procedures to treat congenital or acquired conditions on the hard or soft palate. Its treatment is associated with high recurrence rates. Blood extracts passed by centrifugation are being commonly used for the stimulation of palatal cells for tissue regeneration, promoting faster healing. Case Report: This case report is to describe the case in which platelet-rich fibrin (PRF) membranes were used to close the palatal fistula after flap necrosis. Conclusion: Among the usual blood extracts, PRF has been shown to be effective for adjuvant treatment of palatal fistula healing.

Application of Extracellular Vesicles Derived from Vascular Endothelial/Endothelial Progenitor Cells in Tissue Regeneration and Repair

Extracellular vesicles can be released by almost all types of cells and are important mediators of intercellular signal transmssion. Extracellular vesicles regulate the function and activity of recipient cells by delivering biologically active molecules such as proteins and nucleic acids, which is of great significance in tissue repair and regeneration. According to numerous studies, extracellular vesicles derived from endothelial/endothelial progenitor cells can induce cell proliferation and differentiation, inhibit cell apoptosis, and promote angiogenesis, playing an increasingly important role in regenerative medicine. We reported in this review the latest findings on applying extracellular vesicles derived from endothelial/endothelial progenitor cells in tissue regeneration and repair, and discussed the challenges and future development directions of their application in the field of regenerative medicine.

Secretion of VEGF, TGF-B1 and IGF-1 by Dental- Derived Stem Cells under Hypoxic Conditions

Dental-derived stem cells (DSC) are important cells in tissue regeneration following tissue destruction. One of the environmental conditions in the injured tissue is reduce in oxygen level (hypoxia) but the effect of hypoxia on the DSC is not fully elucidated.

HES1 protein oscillations are necessary for neural stem cells to exit from quiescence

SummaryQuiescence is a dynamic process of reversible cell cycle arrest. High-level persistent expression of the HES1 transcriptional repressor, which oscillates with an ultradian periodicity in proliferative neural stem cells (NSCs), is thought to mediate quiescence. However, it is not known whether this is due to a change in levels or dynamics. Here, we induce quiescence in embryonic NSCs with BMP4, which does not increase HES1 level, and we find that HES1 continues to oscillate. To assess the role of HES1 dynamics, we express persistent HES1 under a moderate strength promoter, which overrides the endogenous oscillations while maintaining the total HES1 level within physiological range. We find that persistent HES1 does not affect proliferation or entry into quiescence; however, exit from quiescence is impeded. Thus, oscillatory expression of HES1 is specifically required for NSCs to exit quiescence, a finding of potential importance for controlling reactivation of stem cells in tissue regeneration and cancer.

The Antioxidant Effects of Ginger Extract on Bioavailability and Oxidative Stress-induced Apoptosis in Mesenchymal Stem Cells of Human Adipose Tissue and Rat Bone Marrow

Background and Aim: Proliferate potential differentiate into different cell lineages and high self-renewal of Mesenchymal Stem Cells (MSCs); thus, they are ideal tools for regenerative medicine. However, a leading problem is an oxidative stress in the target tissue and the apoptosis of transplanted stem cells before tissue repair. The pretreatment of stem cells with antioxidants may make them resistant to oxidative stress. Ginger is the main medicinal plant with antioxidant properties. This study explored the antioxidant effects of ginger extract on bioavailability and oxidative stress-induced apoptosis in human adipose tissue-derived mesenchymal stem cells and rat bone marrow examined. Methods &amp; Materials: In this study, human adipose tissue-derived mesenchymal stem cells and rat bone marrow were cultured in a DMEM medium with 20% FBS. The explored cells were incubated for 4 and 6 hours for pretreatment with different concentrations of ginger extract (50, 100, 200, &amp; 400 mg/mL); then, they were treated with 200 μM H2O2 for 2 hours. Bioavailability was analyzed by ELISA reader using an MTS kit and apoptosis was analyzed by flow cytometry using an Annexin V-FITC/PI kit into the manufacturer’s protocol at both times. The obtained data were analyzed by Analysis of Variance (ANOVA) using SPSS. Ethical Considerations: This study was approved by the Ethics Research Committee of Shahrekord Branch, Islamic Azad University (Code: IR.IAU.SHK.REC.1397.028). Results: The MTS results indicated a dose- and time-dependent manner increase in the bioavailability of human adipose tissue-derived mesenchymal treated stem cells. Ginger extract treatment also dose- and time-dependently decreased the rate of apoptosis in rat bone marrow mesenchymal stem cells. Conclusion: Ginger extract, by reducing the oxidative stress in mesenchymal stem cells, elevates their lifespan in the target tissue, and increases the efficiency of these cells in tissue regeneration.

SDF-1\u03b1 gene-activated collagen scaffold enhances provasculogenic response in a coculture of human endothelial cells with human adipose-derived stromal cells

Novel biomaterials can be used to provide a better environment for cross talk between vessel forming endothelial cells and wound healing instructor stem cells for tissue regeneration. This study seeks to investigate if a collagen scaffold containing a proangiogenic gene encoding for the chemokine stromal-derived factor-1 alpha (SDF-1α GAS) could be used to enhance functional responses in a coculture of human umbilical vein endothelial cells (HUVECs) and human adipose-derived stem/stromal cells (ADSCs). Functional responses were determined by (1) monitoring the amount of junctional adhesion molecule VE-cadherin released during 14 days culture, (2) expression of provasculogenic genes on the 14th day, and (3) the bioactivity of secreted factors on neurogenic human Schwann cells. When we compared our SDF-1α GAS with a gene-free scaffold, the results showed positive proangiogenic determination characterized by a transient yet controlled release of the VE-cadherin. On the 14th day, the coculture on the SDF-1α GAS showed enhanced maturation than its gene-free equivalent through the elevation of provasculogenic genes (SDF-1α—7.4-fold, CXCR4—1.5-fold, eNOS—1.5-fold). Furthermore, we also found that the coculture on SDF-1α GAS secretes bioactive factors that significantly (p < 0.01) enhanced human Schwann cells’ clustering to develop toward Bünger band-like structures. Conclusively, this study reports that SDF-1α GAS could be used to produce a bioactive vascularized construct through the enhancement of the cooperative effects between endothelial cells and ADSCs.

Biomaterials for Recruiting and Activating Endogenous Stem Cells in Tissue Regeneration

Over the past two decades in situ tissue engineering has emerged as a new approach where biomaterials are used to harness the body’s own stem/progenitor cells to regenerate diseased or injured tissue. Biomaterials are designed to recruit resident stem cells to pathological or injured tissue sites and direct them towards tissue regeneration. This review explores advances gathered from in vitro and in vivo studies on in situ tissue regenerative therapies. Here we also examine the different ways this approach has been incorporated into biomaterial sciences in order to create customized biomaterial products for therapeutic applications in a broad spectrum of tissues and diseases.

Macrophages in the pancreas: Villains by circumstances, not necessarily by actions.

IntroductionMounting evidence suggest that macrophages play crucial roles in disease and tissue regeneration. However, despite much efforts during the past decade, our knowledge about the extent of macrophages' contribution to adult pancreatic regeneration after injury or during pancreatic disease progression is still limited. Nevertheless, it is generally accepted that some macrophage features that normally would contribute to healing and regeneration may be detrimental in pancreatic cancer. Altogether, the current literature contains conflicting reports on whether macrophages act as friends or foe in these conditions.Methods and ResultsIn this review, we briefly review the origins of tissue resident and infiltrating macrophages and the importance of cellular crosstalking between macrophages and other resident cells in tissue regeneration. The primary objective of this review is to summarize our knowledge of the distinct roles of tissue resident and infiltrating macrophages, the impact of M1 and M2 macrophage phenotypes, and emerging evidence on macrophage crosstalking in pancreatic injury, regeneration, and disease.ConclusionMacrophages are involved with various stages of pancreatic cancer development, pancreatitis, and diabetes. Elucidating their role in these conditions will aid the development of targeted therapeutic treatments.

Decellularized adipose matrix provides an inductive microenvironment for stem cells in tissue regeneration.

Stem cells play a key role in tissue regeneration due to their self-renewal and multidirectional differentiation, which are continuously regulated by signals from the extracellular matrix (ECM) microenvironment. Therefore, the unique biological and physical characteristics of the ECM are important determinants of stem cell behavior. Although the acellular ECM of specific tissues and organs (such as the skin, heart, cartilage, and lung) can mimic the natural microenvironment required for stem cell differentiation, the lack of donor sources restricts their development. With the rapid development of adipose tissue engineering, decellularized adipose matrix (DAM) has attracted much attention due to its wide range of sources and good regeneration capacity. Protocols for DAM preparation involve various physical, chemical, and biological methods. Different combinations of these methods may have different impacts on the structure and composition of DAM, which in turn interfere with the growth and differentiation of stem cells. This is a narrative review about DAM. We summarize the methods for decellularizing and sterilizing adipose tissue, and the impact of these methods on the biological and physical properties of DAM. In addition, we also analyze the application of different forms of DAM with or without stem cells in tissue regeneration (such as adipose tissue), repair (such as wounds, cartilage, bone, and nerves), in vitro bionic systems, clinical trials, and other disease research.

Migrating Schwann cells direct axon regeneration within the peripheral nerve bridge.

Schwann cells within the peripheral nervous system possess a remarkable regenerative potential. Current research shows that peripheral nerve-associated Schwann cells possess the capacity to promote repair of multiple tissues including peripheral nerve gap bridging, skin wound healing, digit tip repair as well as tooth regeneration. One of the key features of the specialized repair Schwann cells is that they become highly motile. They not only migrate into the area of damaged tissue and become a key component of regenerating tissue but also secrete signaling molecules to attract macrophages, support neuronal survival, promote axonal regrowth, activate local mesenchymal stem cells, and interact with other cell types. Currently, the importance of migratory Schwann cells in tissue regeneration is most evident in the case of a peripheral nerve transection injury. Following nerve transection, Schwann cells from both proximal and distal nerve stumps migrate into the nerve bridge and form Schwann cell cords to guide axon regeneration. The formation of Schwann cell cords in the nerve bridge is key to successful peripheral nerve repair following transection injury. In this review, we first examine nerve bridge formation and the behavior of Schwann cell migration in the nerve bridge, and then discuss how migrating Schwann cells direct regenerating axons into the distal nerve. We also review the current understanding of signals that could activate Schwann cell migration and signals that Schwann cells utilize to direct axon regeneration. Understanding the molecular mechanism of Schwann cell migration could potentially offer new therapeutic strategies for peripheral nerve repair.

Selected Nanomaterials' Application Enhanced with the Use of Stem Cells in Acceleration of Alveolar Bone Regeneration during Augmentation Process.

Regenerative properties are different in every human tissue. Nowadays, with the increasing popularity of dental implants, bone regenerative procedures called augmentations are sometimes crucial in order to perform a successful dental procedure. Tissue engineering allows for controlled growth of alveolar and periodontal tissues, with use of scaffolds, cells, and signalling molecules. By modulating the patient’s tissues, it can positively influence poor integration and healing, resulting in repeated implant surgeries. Application of nanomaterials and stem cells in tissue regeneration is a newly developing field, with great potential for maxillofacial bony defects. Nanostructured scaffolds provide a closer structural support with natural bone, while stem cells allow bony tissue regeneration in places when a certain volume of bone is crucial to perform a successful implantation. Several types of selected nanomaterials and stem cells were discussed in this study. Their use has a high impact on the efficacy of the current and future procedures, which are still challenging for medicine. There are many factors that can influence the regenerative process, while its general complexity makes the whole process even harder to control. The aim of this study was to evaluate the effectiveness and advantage of both stem cells and nanomaterials in order to better understand their function in regeneration of bone tissue in oral cavity.

An Overview on Stem Cells in Tissue Regeneration

Deteriorations in tissues and decline in organ functions, due to chronic diseases or with advancing age or sometimes due to infections or injuries, can severely compromise the quality of life of an individual. Regenerative medicine, a field of medical research focuses on replacing non-functional or dead cells or repairing or regenerating tissues and organs to restore normal functions of an impaired organ. Approaches used in regenerative therapy for achieving the objective employ a number of means which include soluble biomolecules, stem cell transplants, tissue engineering, gene therapy and reprogramming of cells according to target tissue types. Stem cells transplant and tissue regeneration methods for treating various diseases have rapidly grown in usage over the past decades or so. There are different types of stem cells such as mesenchymal, hematopoietic, embryonic, mammary, intestinal, endothelial, neural, olfactory, neural crest, testicular and induced pluripotent stem cells. This review covers the recent advances in tissue regeneration and highlights the application of stem cell transplants in treating many life-threatening diseases or in improving quality of life. Remarkable progress in stem cell research has established that the cell-based therapy could be an option for treating diseases which could not be cured by conventional medical means till recent. Stem cells play major roles in regenerative medicine with its exceptional characteristics of self-renewal capacity and potential to differentiate into almost all types of cells of a body. Vast number of reports on preclinical and clinical application of stem cells revealed its vital role in disease management and many pharmacological industries around the globe working to achieve effective stem cell based products.