Melanocytes in regenerative medicine applications and disease modeling.

Melanocytes are dendritic cells localized in skin, eyes, hair follicles, ears, heart and central nervous system. They are characterized by the presence of melanosomes enriched in melanin which are responsible for skin, eye and hair pigmentation. They also have different functions in photoprotection, immunity and sound perception. Melanocyte dysfunction can cause pigmentary disorders, hearing and vision impairments or increased cancer susceptibility. This review focuses on the role of melanocytes in homeostasis and disease, before discussing their potential in regenerative medicine applications, such as for disease modeling, drug testing or therapy development using stem cell technologies, tissue engineering and extracellular vesicles.

Platelet-Rich Plasma - a remedy present in every human being. History, functioning, and the benefits of therapy using it.

Platelet-rich plasma is an autologous product used in restorative medicine. It contains a high concentration of platelets, which are rich in growth factors and other biologically active substances known for their ability to stimulate regenerative processes in the body. Currently, research is being conducted into the use of platelet-rich plasma in many areas of medicine. This publication provides information on the nature, mechanism of action, therapeutic properties and application of autologous platelet-rich plasma in medicine. Furthermore, ongoing investigations explore its potential in wound healing, orthopedics, dermatology, and even in dentistry, showcasing its versatility and promising outcomes across various medical disciplines. Additionally, the safety and efficacy of platelet-rich plasma therapies are subjects of continual scrutiny, aiming to refine protocols and expand its clinical utility with robust scientific evidence. The growing interest in this regenerative approach underscores its potential as a valuable tool in modern medical practice. Platelet-rich plasma therapy represents a promising avenue for personalized medicine, offering tailored treatment approaches that capitalize on the body's own healing mechanisms to promote tissue repair and regeneration.

Stem Cell-Derived Exosomes: An Advanced Horizon to Cancer Regenerative Medicine.

Cancer research has made significant progress in recent years, and extracellular vesicles (EVs) based cancer investigation reveals several facts about cancer. Exosomes are a subpopulation of EVs. In the present decade, exosomes is mostly highlighted for cancer theranostic research. Tumor cell derived exosomes (TEXs) promote cancer but there are multiple sources of exosomes that can be used as cancer therapeutic agents (plant exosomes, stem cell-derived exosomes, modified or synthetic exosomes). Stem cells based regenerative medicine faces numerous challenges, such as promote tumor development, cellular reprogramming etc., and therefore addressing these complications becomes essential. Stem cell-derived exosomes serves as an answer to these problems and offers a better solution. Global research indicates that stem cell-derived exosomes also play a dual role in the cellular system by either inhibiting or promoting cancer. Modified exosomes which are genetically engineered exosomes or surface modified exosomes to increase the efficacy of the therapeutic properties can also be considered to target the above concerns. However, the difficulties associated with the exosomes include variations in exosomes heterogenity, isolation protocols, large scale production, etc., and these have to be managed effectively. In this review, we explore exosomes biogenesis, multiple stem cell-derived exosome sources, drug delivery, modified stem cells exosomes, clinical trial of stem cells exosomes, and the related challenges in this domain and future orientation. This article may encourage researchers to explore stem cell-derived exosomes and develop an effective and affordable cancer therapeutic solution.

Traditional and emerging strategies using hepatocytes for pancreatic regenerative medicine.

Although pancreas and islet cell transplantation are the only ways to prevent the late complications of insulin-dependent diabetes, a shortage of donors is a major obstacle to tissue and organ transplantation. Stem cell therapy is an effective treatment for diabetes and other pancreatic-related diseases, which can be achieved by inducing their differentiation into insulin-secreting cells. The liver is considered an ideal source of pancreatic cells due to its similar developmental origin and strong regenerative ability as the pancreas. This article reviews the traditional and emerging strategies using hepatocytes for pancreatic regenerative medicine and evaluates their advantages and challenges. Gene reprogramming and chemical reprogramming technologies are traditional strategies with potential to improve the efficiency and specificity of cell reprogramming and promote the transformation of hepatocytes into islet cells. At the same time, organoid technology, as an emerging strategy, has received extensive attention. Biomaterials provide a three-dimensional culture microenvironment for cells, which helps improve cell survival and differentiation efficiency. In addition, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing technology has brought new opportunities and challenges to the development of organoid technology.

The Translation of Nanomedicines in the Contexts of Spinal Cord Injury and Repair.

PURPOSE OF THIS REVIEW: Manipulating or re-engineering the damaged human spinal cord to achieve neuro-recovery is one of the foremost challenges of modern science. Addressing the restricted permission of neural cells and topographically organised neural tissue for self-renewal and spontaneous regeneration, respectively, is not straightforward, as exemplified by rare instances of translational success. This review assembles an understanding of advances in nanomedicine for spinal cord injury (SCI) and related clinical indications of relevance to attempts to design, engineer, and target nanotechnologies to multiple molecular networks. RECENT FINDINGS: Recent research provides a new understanding of the health benefits and regulatory landscape of nanomedicines based on a background of advances in mRNA-based nanocarrier vaccines and quantum dot-based optical imaging. In relation to spinal cord pathology, the extant literature details promising advances in nanoneuropharmacology and regenerative medicine that inform the present understanding of the nanoparticle (NP) biocompatibility-neurotoxicity relationship. In this review, the conceptual bases of nanotechnology and nanomaterial chemistry covering organic and inorganic particles of sizes generally less than 100 nm in diameter will be addressed. Regarding the centrally active nanotechnologies selected for this review, attention is paid to NP physico-chemistry, functionalisation, delivery, biocompatibility, biodistribution, toxicology, and key molecular targets and biological effects intrinsic to and beyond the spinal cord parenchyma. SUMMARY: The advance of nanotechnologies for the treatment of refractory spinal cord pathologies requires an in-depth understanding of neurobiological and topographical principles and a consideration of additional complexities involving the research's translational and regulatory landscapes.

Exploring stem cell frontiers: definitions, challenges, and perspectives for regenerative medicine.

Each year, the European Summer School on Stem Cell Biology and Regenerative Medicine (SCSS) attracts early-career researchers and actively practicing clinicians who specialise in stem cell and regenerative biology. The 16th edition of this influential course took place from 12th to 19th September 2023 on the charming Greek island of Spetses. Focusing on important concepts and recent advances in stem cells, the distinguished faculty included experts spanning the spectrum from fundamental research to clinical trials to market-approved therapies. Alongside an academically intensive programme that bridges the various contexts of stem cell research, delegates were encouraged to critically address relevant questions in stem cell biology and medicine, including broader societal implications. Here, we present a comprehensive overview and key highlights from the SCSS 2023.

Nanotechnological Research for Regenerative Medicine: The Role of Hyaluronic Acid.

Hyaluronic acid (HA) is a linear, anionic, non-sulfated glycosaminoglycan occurring in almost all body tissues and fluids of vertebrates including humans. It is a main component of the extracellular matrix and, thanks to its high water-holding capacity, plays a major role in tissue hydration and osmotic pressure maintenance, but it is also involved in cell proliferation, differentiation and migration, inflammation, immunomodulation, and angiogenesis. Based on multiple physiological effects on tissue repair and reconstruction processes, HA has found extensive application in regenerative medicine. In recent years, nanotechnological research has been applied to HA in order to improve its regenerative potential, developing nanomedical formulations containing HA as the main component of multifunctional hydrogels systems, or as core component or coating/functionalizing element of nanoconstructs. This review offers an overview of the various uses of HA in regenerative medicine aimed at designing innovative nanostructured devices to be applied in various fields such as orthopedics, dermatology, and neurology.

Platelet Concentrates Preconditioning of Mesenchymal Stem Cells and Combined Therapies: Integrating Regenerative Strategies for Enhanced Clinical Applications.

This article presents a comprehensive review of the factors influencing the efficacy of mesenchymal stem cells (MSCs) transplantation and its association with platelet concentrates (PCs). It focuses on investigating the impact of PCs' composition, the age and health status of platelet donors, application methods, and environmental factors on the outcomes of relevant treatments. In addition, it delves into the strategies and mechanisms for optimizing MSCs transplantation with PCs, encompassing preconditioning and combined therapies. Furthermore, it provides an in-depth exploration of the signaling pathways and proteomic characteristics associated with preconditioning and emphasizes the efficacy and specific effects of combined therapy. The article also introduces the latest advancements in the application of biomaterials for optimizing regenerative medical strategies, stimulating scholarly discourse on this subject. Through this comprehensive review, the primary goal is to facilitate a more profound comprehension of the factors influencing treatment outcomes, as well as the strategies and mechanisms for optimizing MSCs transplantation and the application of biomaterials in regenerative medicine, offering theoretical guidance and practical references for related research and clinical practice.

Engineered exosomes and composite biomaterials for tissue regeneration.

Exosomes, which are small vesicles enclosed by a lipid bilayer and released by many cell types, are widely dispersed and have garnered increased attention in the field of regenerative medicine due to their ability to serve as indicators of diseases and agents with therapeutic potential. Exosomes play a crucial role in mediating intercellular communication through the transfer of many biomolecules, including proteins, lipids, RNA, and other molecular constituents, between cells. The targeted transport of proteins and nucleic acids to specific cells has the potential to enhance or impair specific biological functions. Exosomes have many applications, and they can be used alone or in combination with other therapeutic approaches. The examination of the unique attributes and many functions of these factors has emerged as a prominent field of study in the realm of biomedical research. This manuscript summarizes the origins and properties of exosomes, including their structural, biological, physical, and chemical aspects. This paper offers a complete examination of recent progress in tissue repair and regenerative medicine, emphasizing the possible implications of these methods in forthcoming tissue regeneration attempts.

The challenges and prospects of smooth muscle tissue engineering.

Many vascular disorders arise as a result of dysfunctional smooth muscle cells. Tissue engineering strategies have evolved as key approaches to generate functional vascular smooth muscle cells for use in cell-based precision and personalized regenerative medicine approaches. This article highlights some of the challenges that exist in the field and presents some of the prospects for translating research advancements into therapeutic modalities. The article emphasizes the need for better developing synergetic intracellular and extracellular cues in the processes to generate functional vascular smooth muscle cells from different stem cell sources for use in tissue engineering strategies.

This paper explores the potential of engineering smooth muscle tissues to treat vascular diseases, focusing on challenges like sourcing the right cells and creating supportive environments for cell growth. It highlights advances in materials that mimic the body's conditions and the use of 3D fabrication methods for creating complex structures. Additionally, it discusses the significance of mitochondrial function in blood vessel muscle cells. The research emphasizes interdisciplinary efforts and personalized treatments as key to developing effective therapies. The goal is to engineer lab-grown tissues that can repair or replace damaged blood vessels, offering hope for addressing major health challenges associated with vascular diseases.

Exosomes as Promising Therapeutic Tools for Regenerative Endodontic Therapy.

Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not allow for genuine structural regeneration and functional reconstruction of the pulp-dentin complex. In recent years, with the development of tissue engineering and regenerative medicine, research on stem cell-based regenerative endodontic therapy (RET) has achieved satisfactory preliminary results, significantly enhancing its clinical translational prospects. As one of the crucial paracrine effectors, the roles and functions of exosomes in pulp-dentin complex regeneration have gained considerable attention. Due to their advantages of cost-effectiveness, extensive sources, favorable biocompatibility, and high safety, exosomes are considered promising therapeutic tools to promote dental pulp regeneration. Accordingly, in this article, we first focus on the biological properties of exosomes, including their biogenesis, uptake, isolation, and characterization. Then, from the perspectives of cell proliferation, migration, odontogenesis, angiogenesis, and neurogenesis, we aim to reveal the roles and mechanisms of exosomes involved in regenerative endodontics. Lastly, immense efforts are made to illustrate the clinical strategies and influencing factors of exosomes applied in dental pulp regeneration, such as types of parental cells, culture conditions of parent cells, exosome concentrations, and scaffold materials, in an attempt to lay a solid foundation for exploring and facilitating the therapeutic strategy of exosome-based regenerative endodontic procedures.

Intradermal Injection of Hybrid Complexes of High- and Low-Molecular-Weight Hyaluronan: Where Do We Stand and Where Are We Headed in Regenerative Medicine?

Hyaluronic acid (HA) is a remarkably multifaceted biomacromolecule, playing a role in regulating myriad biological processes such as wound healing, tissue regeneration, anti-inflammation, and immunomodulation. Crosslinked high- and low-molecular-weight hyaluronic acid hydrogels achieve higher molar concentrations, display slower degradation, and allow optimal tissue product diffusion, while harnessing the synergistic contribution of different-molecular-weight hyaluronans. A recent innovation in the world of hyaluronic acid synthesis is represented by NAHYCO® Hybrid Technology, a thermal process leading to hybrid cooperative hyaluronic acid complexes (HCC). This review summarizes the current literature on the in vitro studies and in vivo applications of HCC, from facial and body rejuvenation to future perspectives in skin wound healing, dermatology, and genitourinary pathologies.

Collective intelligence: A unifying concept for integrating biology across scales and substrates.

A defining feature of biology is the use of a multiscale architecture, ranging from molecular networks to cells, tissues, organs, whole bodies, and swarms. Crucially however, biology is not only nested structurally, but also functionally: each level is able to solve problems in distinct problem spaces, such as physiological, morphological, and behavioral state space. Percolating adaptive functionality from one level of competent subunits to a higher functional level of organization requires collective dynamics: multiple components must work together to achieve specific outcomes. Here we overview a number of biological examples at different scales which highlight the ability of cellular material to make decisions that implement cooperation toward specific homeodynamic endpoints, and implement collective intelligence by solving problems at the cell, tissue, and whole-organism levels. We explore the hypothesis that collective intelligence is not only the province of groups of animals, and that an important symmetry exists between the behavioral science of swarms and the competencies of cells and other biological systems at different scales. We then briefly outline the implications of this approach, and the possible impact of tools from the field of diverse intelligence for regenerative medicine and synthetic bioengineering.

Unveiling Mechanobiology: A Compact Device for Uniaxial Mechanical Stimulation on Nanofiber Substrates and Its Impact on Cellular Behavior and Nanoparticle Distribution.

Biotechnology and its allied sectors, such as tissue culture, regenerative medicine, and personalized medicine, primarily rely upon extensive studies on cellular behavior and their molecular pathways for generating essential knowledge and innovative strategies for human survival. Most such studies are performed on flat, adherent, plastic-based surfaces and use nanofiber and hydrogel-like soft matrices from the past few decades. However, such static culture conditions cannot mimic the immediate cellular microenvironment, where they perceive or generate a myriad of different mechanical forces that substantially affect their downstream molecular pathways. Including such mechanical forces, still limited to specialized laboratories, using a few commercially available or noncommercial technologies are gathering increasing attention worldwide. However, large-scale consideration and adaptation by developing nations have yet to be achieved due to the lack of a cost-effective, reliable, and accessible solution. Moreover, investigations on cellular response upon uniaxial mechanical stretch cycles under more in vivo mimetic conditions are yet to be studied comprehensively. In order to tackle these obstacles, we have prepared a compact, 3D-printed device using a microcontroller, batteries, sensors, and a stepper motor assembly that operates wirelessly and provides cyclic mechanical attrition to any thin substrate. We have fabricated water-stable and stretchable nanofiber substrates with different fiber orientations by using the electrospinning technique to investigate the impact of mechanical stretch cycles on the morphology and orientation of C2C12 myoblast-like cells. Additionally, we have examined the uptake and distribution properties of BSA-epirubicin nanoparticles within cells under mechanical stimulation, which could act as fluorescently active drug-delivery agents for future therapeutic applications. Consequently, our research offers a comprehensive analysis of cellular behavior when cells are subjected to uniaxial stretching on various nanofiber mat architectures. Furthermore, we present a cost-effective alternative solution that addresses the long-standing requirement for a compact, user-friendly, and tunable device, enabling more insightful outcomes in mechanobiology.

Making Human Hematopoietic Stem Cells Without Transgenes.

Creating hematopoietic stem cells (HSCs) capable of multilineage engraft while possessing the ability to self-renew stands as a pivotal achievement within the field of regenerative medicine. However, achieving the generation of these cells without transgene expression or teratoma formation has not been fully accomplished. In a recent publication featured in Cell Stem Cell, Piau et al. document the production of functional HSCs derived from human-induced pluripotent stem cells (hiPSCs). They achieved this through a one-step differentiation protocol that notably does not require any transgene expression. hiPSCs-derived HSCs can engraft and self-renew upon serial transplantation and they are able to reconstitute lymphoid, myeloid, and erythroid compartments. This study presents a promising system to further study human HSC ontogeny, and it might represent a crucial step to obtain HSCs.

Bioengineering toolkits for potentiating organoid therapeutics.

Organoids are three-dimensional, multicellular constructs that recapitulate the structural and functional features of specific organs. Because of these characteristics, organoids have been widely applied in biomedical research in recent decades. Remarkable advancements in organoid technology have positioned them as promising candidates for regenerative medicine. However, current organoids still have limitations, such as the absence of internal vasculature, limited functionality, and a small size that is not commensurate with that of actual organs. These limitations hinder their survival and regenerative effects after transplantation. Another significant concern is the reliance on mouse tumor-derived matrix in organoid culture, which is unsuitable for clinical translation due to its tumor origin and safety issues. Therefore, our aim is to describe engineering strategies and alternative biocompatible materials that can facilitate the practical applications of organoids in regenerative medicine. Furthermore, we highlight meaningful progress in organoid transplantation, with a particular emphasis on the functional restoration of various organs.

Engineering pre-vascularized 3D tissue and rapid vascular integration with host blood vessels via co-cultured spheroids-laden hydrogel.

Recent advances in regenerative medicine and tissue engineering have enabled the biofabrication of three-dimensional (3D) tissue analogues with the potential for use in transplants and disease modeling. However, the practical use of these biomimetic tissues has been hindered by the challenge posed by reconstructing anatomical-scale micro-vasculature tissues. In this study, we suggest that co-cultured spheroids within hydrogels hold promise for regenerating highly vascularized and innervated tissues, bothin vitroandin vivo. Human adipose-derived stem cells (hADSCs) and human umbilical vein cells (HUVECs) were prepared as spheroids, which were encapsulated in gelatin methacryloyl hydrogels to fabricate a 3D pre-vascularized tissue. The vasculogenic responses, extracellular matrix production, and remodeling depending on parameters like co-culture ratio, hydrogel strength, and pre-vascularization time forin vivointegration with native vessels were then delicately characterized. The co-cultured spheroids with 3:1 ratio (hADSCs/HUVECs) within the hydrogel and with a pliable storage modulus showed the greatest vasculogenic potential, and ultimately formedin vitroarteriole-scale vasculature with a longitudinal lumen structure and a complex vascular network after long-term culturing. Importantly, the pre-vascularized tissue also showed anastomotic vascular integration with host blood vessels after transplantation, and successful vascularization that was positive for both CD31 and alpha-smooth muscle actin covering 18.6 ± 3.6µm2of the luminal area. The described co-cultured spheroids-laden hydrogel can therefore serve as effective platform for engineering 3D vascularized complex tissues.

Advancements in Human Embryonic Stem Cell Research: Clinical Applications and Ethical Issues.

BACKGROUND: The development and use of human embryonic stem cells (hESCs) in regenerative medicine have been revolutionary, offering significant advancements in treating various diseases. These pluripotent cells, derived from early human embryos, are central to modern biomedical research. However, their application is mired in ethical and regulatory complexities related to the use of human embryos. METHOD: This review utilized key databases such as ClinicalTrials.gov, EU Clinical Trials Register, PubMed, and Google Scholar to gather recent clinical trials and studies involving hESCs. The focus was on their clinical application in regenerative medicine, emphasizing clinical trials and research directly involving hESCs. RESULTS: Preclinical studies and clinical trials in various areas like ophthalmology, neurology, endocrinology, and reproductive medicine have demonstrated the versatility of hESCs in regenerative medicine. These studies underscore the potential of hESCs in treating a wide array of conditions. However, the field faces ethical and regulatory challenges, with significant variations in policies and perspectives across different countries. CONCLUSION: The potential of hESCs in regenerative medicine is immense, offering new avenues for treating previously incurable diseases. However, navigating the ethical, legal, and regulatory landscapes is crucial for the continued advancement and responsible application of hESC research in the medical field. Considering both scientific potential and ethical implications, a balanced approach is essential for successfully integrating hESCs into clinical practice.