Exploiting urine-derived induced pluripotent stem cells for advancing precision medicine in cell therapy, disease modeling, and drug testing.

The field of regenerative medicine has witnessed remarkable advancements with the emergence of induced pluripotent stem cells (iPSCs) derived from a variety of sources. Among these, urine-derived induced pluripotent stem cells (u-iPSCs) have garnered substantial attention due to their non-invasive and patient-friendly acquisition method. This review manuscript delves into the potential and application of u-iPSCs in advancing precision medicine, particularly in the realms of drug testing, disease modeling, and cell therapy. U-iPSCs are generated through the reprogramming of somatic cells found in urine samples, offering a unique and renewable source of patient-specific pluripotent cells. Their utility in drug testing has revolutionized the pharmaceutical industry by providing personalized platforms for drug screening, toxicity assessment, and efficacy evaluation. The availability of u-iPSCs with diverse genetic backgrounds facilitates the development of tailored therapeutic approaches, minimizing adverse effects and optimizing treatment outcomes. Furthermore, u-iPSCs have demonstrated remarkable efficacy in disease modeling, allowing researchers to recapitulate patient-specific pathologies in vitro. This not only enhances our understanding of disease mechanisms but also serves as a valuable tool for drug discovery and development. In addition, u-iPSC-based disease models offer a platform for studying rare and genetically complex diseases, often underserved by traditional research methods. The versatility of u-iPSCs extends to cell therapy applications, where they hold immense promise for regenerative medicine. Their potential to differentiate into various cell types, including neurons, cardiomyocytes, and hepatocytes, enables the development of patient-specific cell replacement therapies. This personalized approach can revolutionize the treatment of degenerative diseases, organ failure, and tissue damage by minimizing immune rejection and optimizing therapeutic outcomes. However, several challenges and considerations, such as standardization of reprogramming protocols, genomic stability, and scalability, must be addressed to fully exploit u-iPSCs' potential in precision medicine. In conclusion, this review underscores the transformative impact of u-iPSCs on advancing precision medicine and highlights the future prospects and challenges in harnessing this innovative technology for improved healthcare outcomes.

[Autologous platelet concentrates in regenerative dentistry - A narrative literature review. Part II: clinical application of PRF in periodontology and implantology].

The clinical impact of platelet-rich fibrin (PRF) and plasma rich in growth factors (PRGF®) respectively has been studied extensively in the field of regenerative dentistry during the last two decades. Literature supports evidence for additional benefits in regenerative periodontal therapy, alveolar ridge preservation, management of extraction sockets, implantology including guided bone regeneration as well as defect management in oral surgery. Regarding gingival wound healing and soft tissue regeneration, there is sufficient evidence for their positive effects which have been confirmed in several systematic reviews. The effects seem less clear in conjunction with osseous regenerative treatments, where the inter-study heterogenity in terms of different PRF-protocols, indications and application forms might hinder a systematic comparison. Nevertheless there is evidence that PRF might have beneficial effects on hard-tissue or its regeneration respectively.For being able to facilitate conclusions in systematic reviews, precise reporting of the used PRF-protocols is mandatory for future (clinical) research in the field of autologous platelet concentrates.

Mesenchymal Stem Cells and Their Role in Neurodegenerative Diseases.

Mesenchymal stem cells (MSCs) have garnered significant interest in the field of regenerative medicine for their ability to potentially treat various diseases, especially neurodegenerative disorders [...].

Cryo-storage of porcine hides at the industrial scale for tissue engineering and regenerative medicine application.

BACKGROUND: The industrial scale cryo-storage of raw tissue materials requires a robust, low-cost and easy-to-operate method that can facilitate the down-stream process. OBJECTIVE: The study was aimed to develop the multifunctional protective solutions (MPS) for transportation at ambient conditions and also subsequent cryo-storage below -20 degree C of raw porcine hides for tissue engineering and regenerative medicine. MATERIALS AND METHODS: Protective solutions with antimicrobial activity and proteinase-inhibiting activity were developed and tested for its efficacy in preserving the extracellular matrix of porcine dermis from microbial spoilage, proteolytic degradation, freeze damage and excessive dehydration during shipping and cryo-storage. The MPSs contained phosphate-buffered saline with ethylene diamine tetra acetic acid (EDTA) added as chelator and proteinase inhibitor, as well as glycerol or maltodextrin (M180) as cryoprotectants. RESULTS: MPSs prepared with EDTA and glycerol or M180 had significant antimicrobial activity and proteinase-inhibiting activity during the period of shipping and handling. Glycerol and M180 prevented eutectic salt precipitation and excessive freeze dehydration upon cryo-storage of porcine hides. Without glycerol or M180, hides could be freeze-dehydrated to the low hydration at ~0.4 g/g dw, and formed irreversible plications after freezing. A critical hydration (0.8~0.9 g/g dw) was observed for the extracellular matrix of porcine dermis, and dehydration to a lower level could impose enormous stress and potential damage. The soaking of porcine hides in MPSs decreased water content as glycerol and M180 entered into dermis. Upon equilibration, the glycerol content in the tissue was about 94% of the incubating glycerol solution, but the M180 content in the tissue was only about 50% of the incubating M180 solution, indicating that M180 did not get into the entire aqueous domain within dermis. MPSs reduced ice formation and increased the unfrozen water content of porcine raw hides upon cryo-storage. CONCLUSION: MPSs prepared with EDTA and glycerol or M180 have antimicrobial activity and proteinase-inhibiting activity, which can be used for transportation and cryo-storage of raw hides at the industrial scale. Glycerol at 7.5% w/v and M180 at 20% w/v were sufficient to prevent freeze damage and excessive freeze dehydration. Doi.org/10.54680/fr24310110312.

The hope, hype and obstacles surrounding cell therapy.

Cell therapy offers hope, but it also presents challenges, most particularly the limited ability of human organs and tissues to regenerate. Since many diseases are associated with irreversible pathophysiological or traumatic changes, stem cells and their derivatives are unable to secure healing. Although regenerative medicine offers chances for improvements in many diseases, such as type one diabetes and Parkinson's disease, it cannot eliminate the primary cause of many of them. While successes can be expected for diseases such as sickle cell disease, this is not the case for hereditary diseases with varied mutation types or for ciliopathies, which start in embryogenesis. In this complicated medical environment, synthetic biology offers some solutions, but their implementation will take many years. Still, positive examples such as CAR-T therapy offer hope.

The use of artificial intelligence in induced pluripotent stem cell-based technology over 10-year period: A systematic scoping review.

BACKGROUND: Stem cell research, particularly in the domain of induced pluripotent stem cell (iPSC) technology, has shown significant progress. The integration of artificial intelligence (AI), especially machine learning (ML) and deep learning (DL), has played a pivotal role in refining iPSC classification, monitoring cell functionality, and conducting genetic analysis. These enhancements are broadening the applications of iPSC technology in disease modelling, drug screening, and regenerative medicine. This review aims to explore the role of AI in the advancement of iPSC research. METHODS: In December 2023, data were collected from three electronic databases (PubMed, Web of Science, and Science Direct) to investigate the application of AI technology in iPSC processing. RESULTS: This systematic scoping review encompassed 79 studies that met the inclusion criteria. The number of research studies in this area has increased over time, with the United States emerging as a leading contributor in this field. AI technologies have been diversely applied in iPSC technology, encompassing the classification of cell types, assessment of disease-specific phenotypes in iPSC-derived cells, and the facilitation of drug screening using iPSC. The precision of AI methodologies has improved significantly in recent years, creating a foundation for future advancements in iPSC-based technologies. CONCLUSIONS: Our review offers insights into the role of AI in regenerative and personalized medicine, highlighting both challenges and opportunities. Although still in its early stages, AI technologies show significant promise in advancing our understanding of disease progression and development, paving the way for future clinical applications.

[Cell technologies as a basis for the development of regenerative principles for the treatment of lacrimal gland diseases]. / Kletochnye tekhnologii kak osnova razrabotki regeneratornykh printsipov lecheniya zabolevanii sleznoi zhelezy.

The lacrimal gland (LG) is a tubuloacinar exocrine gland composed of acinar, ductal, and myoepithelial cells. Three-dimensional distribution of acinar lobules, ducts, and myoepithelial cells is necessary for the effective functioning of the organ. LG is the main organ of immune surveillance of the ocular surface system. The embryogenesis of the gland is regulated by the interaction of genetic mechanisms, internal epigenetic (enzyme systems, hormones) and exogenous factors. There is no doubt that there is a clear genetic program for the implementation of the complex process of embryonic development. The mechanisms regulating LG organogenesis initiate the work of a huge number of structural oncogenes, transcription and growth factors, etc. Studying the expression and selective activity of regulatory genes during organ development, their participation in the differentiation of different cell types is a current trend at the nexus of clinical genetics, molecular biology, embryology and immunocytochemistry. Due to its relatively simple structure and accessibility, human LG is a suitable object for potential application in regenerative medicine. Development of a universal protocol for obtaining functional differentiated secretory epithelium of LG capable of expressing tissue-specific markers is an urgent task. Determining the nature and origin of stem cells and progenitor cells will allow the isolation and multiplication of these cells in culture. After obtaining a functionally active culture of LG cells, it is possible to create a model of autoimmune diseases.

Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration-Part II.

During the last three decades, mesenchymal stem/stromal cells (MSCs) were extensively studied, and are mainly considered within the setting of their regenerative and immunomodulatory properties in tissue regeneration [...].

Synthesis and Physicochemical Characterization of Gelatine-Based Biodegradable Aerogel-like Composites as Possible Scaffolds for Regenerative Medicine.

Regenerative medicine is an interdisciplinary field aiming at restoring pathologically damaged tissues and whole organs by cell transplantation in combination with proper supporting scaffolds. Gelatine-based ones are very attractive due to their biocompatibility, rapid biodegradability, and lack of immunogenicity. Gelatine-based composite hydrogels, containing strengthening agents to improve their modest mechanical properties, have been demonstrated to act as extracellular matrices (ECMs), thus playing a critical role in "organ manufacturing". Inspired by the lysyl oxidase (LO)-mediated process of crosslinking, which occurs in nature to reinforce collagen, we have recently developed a versatile protocol to crosslink gelatine B (Gel B) in the presence or absence of LO, using properly synthesized polystyrene- and polyacrylic-based copolymers containing the amine or aldehyde groups needed for crosslinking reactions. Here, following the developed protocol with slight modifications, we have successfully crosslinked Gel B in different conditions, obtaining eight out of nine compounds in high yield (57-99%). The determined crosslinking degree percentage (CP%) evidenced a high CP% for compounds obtained in presence of LO and using the styrenic amine-containing (CP5/DMAA) and acrylic aldehyde-containing (CPMA/DMAA) copolymers as crosslinking agents. ATR-FTIR analyses confirmed the chemical structure of all compounds, while optical microscopy demonstrated cavernous, crater-like, and labyrinth-like morphologies and cavities with a size in the range 15-261 µm. An apparent density in the range 0.10-0.45 g/cm3 confirmed the aerogel-like structure of most samples. Although the best biodegradation profile was observed for the sample obtained using 10% CP5/DMAA (M3), high swelling and absorption properties, high porosity, and good biodegradation profiles were also observed for samples obtained using the 5-10% CP5/DMAA (M4, 5, 6) and 20% CPMA/DMAA (M9) copolymers. Collectively, in this work of synthesis and physicochemical characterization, new aerogel-like composites have been developed and, based on their characteristics, which fit well within the requirements for TE, five candidates (M3, M4, M5, M6, and M9) suitable for future biological experiments on cell adhesion, infiltration and proliferation, to confirm their effective functioning, have been identified.

Stem-Cell-Driven Chondrogenesis: Perspectives on Amnion-Derived Cells.

Regenerative medicine harnesses stem cells' capacity to restore damaged tissues and organs. In vitro methods employing specific bioactive molecules, such as growth factors, bio-inductive scaffolds, 3D cultures, co-cultures, and mechanical stimuli, steer stem cells toward the desired differentiation pathways, mimicking their natural development. Chondrogenesis presents a challenge for regenerative medicine. This intricate process involves precise modulation of chondro-related transcription factors and pathways, critical for generating cartilage. Cartilage damage disrupts this process, impeding proper tissue healing due to its unique mechanical and anatomical characteristics. Consequently, the resultant tissue often forms fibrocartilage, which lacks adequate mechanical properties, posing a significant hurdle for effective regeneration. This review comprehensively explores studies showcasing the potential of amniotic mesenchymal stem cells (AMSCs) and amniotic epithelial cells (AECs) in chondrogenic differentiation. These cells exhibit innate characteristics that position them as promising candidates for regenerative medicine. Their capacity to differentiate toward chondrocytes offers a pathway for developing effective regenerative protocols. Understanding and leveraging the innate properties of AMSCs and AECs hold promise in addressing the challenges associated with cartilage repair, potentially offering superior outcomes in tissue regeneration.

Induced Pluripotent Stem Cells and Organoids in Advancing Neuropathology Research and Therapies.

This review delves into the groundbreaking impact of induced pluripotent stem cells (iPSCs) and three-dimensional organoid models in propelling forward neuropathology research. With a focus on neurodegenerative diseases, neuromotor disorders, and related conditions, iPSCs provide a platform for personalized disease modeling, holding significant potential for regenerative therapy and drug discovery. The adaptability of iPSCs, along with associated methodologies, enables the generation of various types of neural cell differentiations and their integration into three-dimensional organoid models, effectively replicating complex tissue structures in vitro. Key advancements in organoid and iPSC generation protocols, alongside the careful selection of donor cell types, are emphasized as critical steps in harnessing these technologies to mitigate tumorigenic risks and other hurdles. Encouragingly, iPSCs show promising outcomes in regenerative therapies, as evidenced by their successful application in animal models.

Stem Cell and Regenerative Therapies for the Treatment of Osteoporotic Vertebral Compression Fractures.

Osteoporotic vertebral compression fractures (OVCFs) significantly increase morbidity and mortality, presenting a formidable challenge in healthcare. Traditional interventions such as vertebroplasty and kyphoplasty, despite their widespread use, are limited in addressing the secondary effects of vertebral fractures in adjacent areas and do not facilitate bone regeneration. This review paper explores the emerging domain of regenerative therapies, spotlighting stem cell therapy's transformative potential in OVCF treatment. It thoroughly describes the therapeutic possibilities and mechanisms of action of mesenchymal stem cells against OVCFs, relying on recent clinical trials and preclinical studies for efficacy assessment. Our findings reveal that stem cell therapy, particularly in combination with scaffolding materials, holds substantial promise for bone regeneration, spinal stability improvement, and pain mitigation. This integration of stem cell-based methods with conventional treatments may herald a new era in OVCF management, potentially improving patient outcomes. This review advocates for accelerated research and collaborative efforts to translate laboratory breakthroughs into clinical practice, emphasizing the revolutionary impact of regenerative therapies on OVCF management. In summary, this paper positions stem cell therapy at the forefront of innovation for OVCF treatment, stressing the importance of ongoing research and cross-disciplinary collaboration to unlock its full clinical potential.

Organoid bioinks: construction and application.

Organoids have emerged as crucial platforms in tissue engineering and regenerative medicine but confront challenges in faithfully mimicking native tissue structures and functions. Bioprinting technologies offer a significant advancement, especially when combined with organoid bioinks-engineered formulations designed to encapsulate both the architectural and functional elements of specific tissues. This review provides a rigorous, focused examination of the evolution and impact of organoid bioprinting. It emphasizes the role of organoid bioinks that integrate key cellular components and microenvironmental cues to more accurately replicate native tissue complexity. Furthermore, this review anticipates a transformative landscape invigorated by the integration of artificial intelligence with bioprinting techniques. Such fusion promises to refine organoid bioink formulations and optimize bioprinting parameters, thus catalyzing unprecedented advancements in regenerative medicine. In summary, this review accentuates the pivotal role and transformative potential of organoid bioinks and bioprinting in advancing regenerative therapies, deepening our understanding of organ development, and clarifying disease mechanisms.

CRISPR Advancements for Human Health.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) has emerged as a powerful gene editing technology that is revolutionizing biomedical research and clinical medicine. The CRISPR system allows scientists to rewrite the genetic code in virtually any organism. This review provides a comprehensive overview of CRISPR and its clinical applications. We first introduce the CRISPR system and explain how it works as a gene editing tool. We then highlight current and potential clinical uses of CRISPR in areas such as genetic disorders, infectious diseases, cancer, and regenerative medicine. Challenges that need to be addressed for the successful translation of CRISPR to the clinic are also discussed. Overall, CRISPR holds great promise to advance precision medicine, but ongoing research is still required to optimize delivery, efficacy, and safety.

3D bioprinting: a review and potential applications for Mohs micrographic surgery.

Mohs Micrographic Surgery (MMS) is effective for treating common cutaneous malignancies, but complex repairs may often present challenges for reconstruction. This paper explores the potential of three-dimensional (3D) bioprinting in MMS, offering superior outcomes compared to traditional methods. 3D printing technologies show promise in advancing skin regeneration and refining surgical techniques in dermatologic surgery. A PubMed search was conducted using the following keywords: "Three-dimensional bioprinting" OR "3-D printing" AND "Mohs" OR "Mohs surgery" OR "Surgery." Peer-reviewed English articles discussing medical applications of 3D bioprinting were included, while non-peer-reviewed and non-English articles were excluded. Patients using 3D MMS models had lower anxiety scores (3.00 to 1.7, p < 0.0001) and higher knowledge assessment scores (5.59 or 93.25% correct responses), indicating better understanding of their procedure. Surgical residents using 3D models demonstrated improved proficiency in flap reconstructions (p = 0.002) and knowledge assessment (p = 0.001). Additionally, 3D printing offers personalized patient care through tailored surgical guides and anatomical models, reducing intraoperative time while enhancing surgical. Concurrently, efforts in tissue engineering and regenerative medicine are being explored as potential alternatives to address organ donor shortages, eliminating autografting needs. However, challenges like limited training and technological constraints persist. Integrating optical coherence tomography with 3D bioprinting may expedite grafting, but challenges remain in pre-printing grafts for complex cases. Regulatory and ethical considerations are paramount for patient safety, and further research is needed to understand long-term effects and cost-effectiveness. While promising, significant advancements are necessary for full utilization in MMS.

Regenerative Medicine in Gynecology.

The female reproductive tract undergoes dynamic changes across the life span. Congenital abnormalities, life events, and medical interventions can negatively affect the structure and function of reproductive tract organs, resulting in lifelong sequelae. The objective of regenerative gynecology is to discover and promote endogenous mechanisms by which a healthy tissue maintains overall tissue integrity after injury, after disease, or with age. In this review, we discuss some of the key state-of-the-art cell-based and scaffolding therapies that have been applied to regenerate gynecologic tissues and organs primarily in animal and tissue culture models. We further discuss the limitations of current technologies, problems of implementation and scalability, and future outlook of the field.

Exosome-loaded decellularized tissue: Opening a new window for regenerative medicine.

Mesenchymal stem cell-derived exosomes (MSCs-EXO) have received a lot of interest recently as a potential therapeutic tool in regenerative medicine. Extracellular vesicles (EVs) known as exosomes (EXOs) are crucial for cell-cell communication throughout a variety of activities including stress response, aging, angiogenesis, and cell differentiation. Exploration of the potential use of EXOs as essential therapeutic effectors of MSCs to encourage tissue regeneration was motivated by success in the field of regenerative medicine. EXOs have been administered to target tissues using a variety of methods, including direct, intravenous, intraperitoneal injection, oral delivery, and hydrogel-based encapsulation, in various disease models. Despite the significant advances in EXO therapy, various methods are still being researched to optimize the therapeutic applications of these nanoparticles, and it is not completely clear which approach to EXO administration will have the greatest effects. Here, we will review emerging developments in the applications of EXOs loaded into decellularized tissues as therapeutic agents for use in regenerative medicine in various tissues.

Therapeutic applications of mesenchymal/medicinal stem/signaling cells preconditioned with external factors: Are there more efficient approaches to utilize their regenerative potential?

Mesenchymal/medicinal stem/signaling cells (MSCs) have emerged as a promising treatment option for various disorders. However, the donor's age, advanced stage of disease, and prolonged in vitro expansion often diminish the innate regenerative potential of MSCs. Besides that, the absence of MSCs' comprehensive "pre-admission testing" can result in the injection of cells with reduced viability and function, which may negatively affect the overall outcome of MSC-based therapies. It is, therefore, essential to develop effective strategies to improve the impaired biological performance of MSCs. This review focuses on the comprehensive characterization of various methods of external MSCs stimulation (hypoxia, heat shock, caloric restriction, acidosis, 3D culture, and application of extracellular matrix) that augment their medicinal potential. To emphasize the significance of MSCs priming, we summarize the effects of individual and combined preconditioning approaches, highlighting their impact on MSCs' response to either physiological or pathological conditions. We further investigate the synergic action of exogenous factors to maximize MSCs' therapeutic potential. Not to omit the field of tissue engineering, the application of pretreated MSCs seeded on scaffolds is discussed as well.

Advanced Smart Biomaterials for Regenerative Medicine and Drug Delivery Based on Phosphoramidite Chemistry: From Oligonucleotides to Precision Polymers.

Over decades of development, while phosphoramidite chemistry has been known as the leading method in commercial synthesis of oligonucleotides, it has also revolutionized the fabrication of sequence-defined polymers (SDPs), offering novel functional materials in polymer science and clinical medicine. This review has introduced the evolution of phosphoramidite chemistry, emphasizing its development from the synthesis of oligonucleotides to the creation of universal SDPs, which have unlocked the potential for designing programmable smart biomaterials with applications in diverse areas including data storage, regenerative medicine and drug delivery. The key methodologies, functions, biomedical applications, and future challenges in SDPs, have also been summarized in this review, underscoring the significance of breakthroughs in precisely synthesized materials.

Induced pluripotent stem cells in cartilage tissue engineering: a literature review.

Osteoarthritis (OA) is a long-term, persistent joint disorder characterized by bone and cartilage degradation, resulting in tightness, pain, and restricted movement. Current attempts in cartilage regeneration are cell-based therapies using stem cells. Multipotent stem cells, such as mesenchymal stem cells (MSCs), and pluripotent stem cells, such as embryonic stem cells (ESCs), have been used to regenerate cartilage. However, since the discovery of human-induced pluripotent stem cells (hiPSCs) in 2007, it was seen as a potential source for regenerative chondrogenic therapy as it overcomes the ethical issues surrounding the use of ESCs and the immunological and differentiation limitations of MSCs. This literature review focuses on chondrogenic differentiation and 3D bioprinting technologies using hiPSCS, suggesting them as a viable source for successful tissue engineering. METHODS: A literature search was conducted using scientific search engines, PubMed, MEDLINE, and Google Scholar databases with the terms 'Cartilage tissue engineering' and 'stem cells' to retrieve published literature on chondrogenic differentiation and tissue engineering using MSCs, ESCs, and hiPSCs. RESULTS: hiPSCs may provide an effective and autologous treatment for focal chondral lesions, though further research is needed to explore the potential of such technologies. CONCLUSIONS: This review has provided a comprehensive overview of these technologies and the potential applications for hiPSCs in regenerative medicine.