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Schematic illustration of embryonic organogenesis and approaches for organ regeneration. (a) Schematic diagram of organogenesis. A functional organ is developed through the establishment of organ-forming fields, formation of organ germs by reciprocal epithelial and mesenchymal interactions, and morphogenesis. (b) Scheme of the fully functional regeneration of an ectodermal organ by mimicking organ germ formation using embryonic fate-determined epithelial and mesenchymal stem cells with organ-inductive potential. (c) Schematic illustration of organoid generation by recapitulating the establishment of organ-forming fields in cell masses generated from pluripotent stem cells.
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In this decade, substantial progress in the fields of developmental biology and stem cell biology has ushered in a new era for three-dimensional organ regenerative therapy. The emergence of novel three-dimensional cell manipulation technologies enables the effective mimicking of embryonic organ germ formation using the fate-determined organ-inducti...
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Introduction
Acute kidney injury (AKI) is a common and severe clinical problem that is associated with high mortality, a long hospital stays and high healthcare resource consumption. Approximately a quarter of AKI survivors will develop chronic kidney disease. Mesenchymal stem cells (MSCs) are multipotent stem cells with antiapoptotic, immunomodula...
Ischemia-reperfusion injury is an important contributor to acute kidney injury and a major factor affecting early functional recovery after kidney transplantation. We conducted this experiment to investigate the protective effect of induced multipotent stem cell transplantation on renal ischemia-reperfusion injury. Forty rabbits were divided into f...
Neural stem cells (NSCs) are multipotent stem cells that reside in the fetal and adult mammalian brain, which can self-renew and differentiate into neurons and supporting cells. Intrinsic and extrinsic cues, from cells in the local niche and from distant sites, stringently orchestrates the self-renewal and differentiation competence of NSCs. Ample...
Adipose-derived mesenchymal stromal cells (ASCs) are multipotent stem cells which can differentiate into various cell types, including osteocytes and adipocytes. Due to their ease of harvesting, multipotency, and low tumorigenicity, they are a prime candidate for the development of novel interventional approaches in regenerative medicine. ASCs exhi...
Citations
... However, improvement of salivary gland hypofunction may be limited [21]. Exciting prospects for future therapeutic options lie in the fields of developmental and stem cell biology [22]. Recently, guidelines for nonnutritional therapies for xerostomia have been published by The Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology, and the American Society of Clinical Oncology [11]. ...
Xerostomia and hyposalivation are highly prevalent conditions in old age, particularly among multimorbid elders, and are often attributed to the use of multiple medications. These conditions negatively affect oral functions, such as chewing, swallowing, speech, and taste. Additionally, the lack of lubrication of the oral mucosa frequently leads to super-infections with candida. Denture retention and comfort may also be compromised. The risk of dental caries and erosion of natural teeth increases since saliva, which is essential for repairing initial lesions in tooth structures, is insufficient. The dry sensation in the mouth also impacts the emotional and social well-being of elderly individuals. Patients experiencing xerostomia often avoid certain foods that are uncomfortable or difficult to consume. However, some foods may alleviate the symptoms or even stimulate salivation. This review discusses the limited available evidence on nutritional advice for patients with xerostomia and aims to provide insight into the patient’s perspective while offering clinical recommendations. Future studies should focus on investigating the nutritional intake of individuals suffering from xerostomia or hyposalivation in order to ensure oral health comfort, prevent malnutrition, and minimize the impact on their quality of life.
... The current study provides evidence of the successful replacement of a functional organ through orthotopic transplantation of a self-organized organ rudiment generated from pluripotent stem cells [66]. This study will contribute to the future development of next-generation organ replacement regenerative therapy using PSCs. ...
Dry mouth results from hypofunction of the salivary glands due to Sjögren's syndrome (SS), various medications, and radiation therapy for head and neck cancer. In severe cases of salivary gland hypofunction, sialagogues are not always effective due to the loss of salivary parenchyma. Therefore, regenerative medicine using stem cell therapy is a promising treatment for severe cases. Stem cells are classified into three groups: tissue stem cells, embryonic stem cells, and induced pluripotent stem cells. Tissue stem cells, such as hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and salivary stem/progenitor cells, could rescue irradiation-induced salivary gland hypofunction. Both HSCs and MSCs can rescue salivary gland hypofunction through soluble factors in a paracrine manner, while salivary stem/progenitor cells can reconstitute the damaged salivary glands. In fact, we clarified that CD133-positive cells in mouse submandibular glands showed stem cell features, which reconstituted the damaged salivary glands. Furthermore, we focused on the challenge of producing functional salivary glands that are three-dimensionally induced from mouse ES cells.
... Therefore, development of alternative treatments to restore salivary gland secretory function is critical. Several experimental therapies including the use of stem cells (Nanduri et al., 2011;Nanduri et al., 2013;Pringle et al., 2013;Mitroulia et al., 2019;Su et al., 2020), embryonic organ culture (Ogawa et al., 2013;Ogawa and Tsuji, 2015;Ikeda et al., 2019), organ bioprinting (Ferreira et al., 2016;Adine et al., 2018), cell sheets (Nam et al., 2019a;dos Santos et al., 2020), gene therapy (Zheng et al., 2011;Baum et al., 2012;Arany et al., 2013) and bioengineered scaffolds (Peters et al., 2014;Foraida et al., 2017;Patil and Nanduri, 2017;Nam et al., 2019b) have offered the promise of more advanced solutions as detailed below. ...
Previous studies demonstrated that salivary gland morphogenesis and differentiation are enhanced by modification of fibrin hydrogels chemically conjugated to Laminin-1 peptides. Specifically, Laminin-1 peptides (A99: CGGALRGDN-amide and YIGSR: CGGADPGYIGSRGAA-amide) chemically conjugated to fibrin promoted formation of newly organized salivary epithelium both in vitro (e.g., using organoids) and in vivo (e.g., in a wounded mouse model). While these studies were successful, the model’s usefulness for inducing regenerative patterns after radiation therapy remains unknown. Therefore, the goal of the current study was to determine whether transdermal injection with the Laminin-1 peptides A99 and YIGSR chemically conjugated to fibrin hydrogels promotes tissue regeneration in irradiated salivary glands. Results indicate that A99 and YIGSR chemically conjugated to fibrin hydrogels promote formation of functional salivary tissue when transdermally injected to irradiated salivary glands. In contrast, when left untreated, irradiated salivary glands display a loss in structure and functionality. Together, these studies indicate that fibrin hydrogel-based implantable scaffolds containing Laminin-1 peptides promote secretory function of irradiated salivary glands.
... Since data obtained from 2D cultured cells are only limitedly transferable to the in vivo situation, 3D settings are developed to more closely mimic the respective tissue [190]. Three-dimensional (3D) culture systems without scaffolds include spheroids, aggregate formation, but also organoids and organ germs [191,192]. ...
... Both were tremendous steps toward modeling of tissue development and tissue regeneration. In embryogenesis, organ germs give rise to organs and are often the result of reciprocal interactions of mesenchyme and epithelium, which are already fate determined by so-called organ-forming fields [192]. The first report of a dental "organ germ" was in 2007, where epithelial and mesenchymal cells were isolated from an embryonic tooth germ. ...
... By the compartmentalization of mesenchymal and epithelial cells in high density, Nakao and colleagues were able to replicate the induction of tooth germs. In subsequent publications, they showed that it was possible to generate also other functional ectodermal organs [192][193][194][195][196][197][198]. They also reported that the bioengineered tooth germ has the potential to erupt from a region of a lost tooth in mice [194]. ...
Dental stem cells have been isolated from the medical waste of various dental tissues. They have been characterized by numerous markers, which are evaluated herein and differentiated into multiple cell types. They can also be used to generate cell lines and iPSCs for long-term in vitro research. Methods for utilizing these stem cells including cellular systems such as organoids or cell sheets, cell-free systems such as exosomes, and scaffold-based approaches with and without drug release concepts are reported in this review and presented with new pictures for clarification. These in vitro applications can be deployed in disease modeling and subsequent pharmaceutical research and also pave the way for tissue regeneration. The main focus herein is on the potential of dental stem cells for hard tissue regeneration, especially bone, by evaluating their potential for osteogenesis and angiogenesis, and the regulation of these two processes by growth factors and environmental stimulators. Current in vitro and in vivo publications show numerous benefits of using dental stem cells for research purposes and hard tissue regeneration. However, only a few clinical trials currently exist. The goal of this review is to pinpoint this imbalance and encourage scientists to pick up this research and proceed one step further to translation.
... Tissue regeneration as the second generation of regenerative medicine utilizes adult stem cells derived from patients; this is still under clinical trial to cure different tissue degeneration [230,231]. The next generation of regenerative therapy as an organ replacement therapy targets the whole organs through multiple cell types with a complex 3D structure [232]. Investigators have placed immense efforts on regenerating organs by integrating functional cells and 3D scaffold as the new approach in tissue engineering, however, this strategy encountered some limitations, such as low efficiency of organ induction and uncontrollable direction and size of the regenerated organ [233,234]. ...
Organoids are powerful systems to facilitate the study of individuals' disorders and personalized treatments. Likewise, emerging this technology has improved the chance of translatability of drugs for pre-clinical therapies and mimicking the complexity of organs, while it proposes numerous approaches for human disease modeling, tissue engineering, drug development, diagnosis, and regenerative medicine. In this review, we outline the past/present organoid technology and summarize its faithful applications, then, we discuss the challenges and limitations encountered by 3D organoids. In the end, we offer the human organoids as basic mechanistic infrastructure for "human modelling" systems to prescribe personalized medicines. © AlphaMed Press 2021 SIGNIFICANCE STATEMENT: This concise review concerns about organoids, available methods for in vitro organoid formation and different types of human organoid models. We, then, summarize biological approaches to improve 3D organoids complexity and therapeutic potentials of organoids. Despite the existing incomprehensive review articles in literature that examine partial aspects of the organoid technology, the present review article comprehensively and critically presents this technology from different aspects. It effectively provides a systematic overview on the past and current applications of organoids and discusses the future perspectives and suggestions to improve this technology and its applications.
... Pendant la vie intra-utérine, l'embryogenèse de la molaire de souris comporte les stades suivants [53,134] odontoblastes sécrètent une matrice extracellulaire collagénique qui est ensuite minéralisée pour former la dentine [53,134]. ...
... Pendant la vie intra-utérine, l'embryogenèse de la molaire de souris comporte les stades suivants [53,134] odontoblastes sécrètent une matrice extracellulaire collagénique qui est ensuite minéralisée pour former la dentine [53,134]. ...
... Schéma du développement dentaire (selonIkeda et al., 2019) [53]. ...
La régénération tissulaire est un domaine en pleine expansion en odontologie et a pour principal objectif de remplacer les tissus dentaires lésés ou absents. Il existe différentes approches basées sur la régénération d'un type tissulaire particulier constituant la dent (émail, dentine, pulpe), du parodonte (cément, os alvéolaire, ligament alvéolo-dentaire) ou encore d'une dent entière. Dans cette perspective, la vascularisation et l'innervation de la dent sont essentielles pour le maintien de l'homéostasie et la réponse aux stimuli nociceptifs. Ce travail de thèse s’articule autour de trois grandes thématiques : la régénération de la dent et son innervation, la préparation d’un site osseux propice à son développement et enfin son éruption dans la cavité buccale, la régénération tissulaire n’ayant de sens que lorsque l’organe est fonctionnel.
... ASC-based organoids more closely recapitulate the homeostatic conditions and regenerative processes of the corresponding tissues, with a microscopic architecture closer to that of adult tissue (Clevers, 2016). Unfortunately, this restricted potential compared to PSCs means that ASCs lack the necessary tissue-tissue interactions to promote organ-level complexity, such as in the formation of organ buds derived from reciprocal epithelial and mesenchymal interactions (Ikeda et al., 2019). As another example, vilification of the small intestine is believed to be initiated by mesenchymal clustering beneath the intestinal epithelium and subsequent modification of the mechanobiological environment around the epithelium . ...
... Applying the same concept of organogenesis guided by multilineage interactions, complex oral organs were fabricated by leveraging epithelial-mesenchymal cross-talk and its inherent ability to guide organ germ formation at the interface (Ikeda et al., 2019). This bioengineering strategy consisted of mixing epithelial and mesenchymal stem cells isolated from the mouse embryo and injecting them into collagen gels. ...
Organoids form through self-organization processes in which initially homogeneous populations of stem cells spontaneously break symmetry and undergo in-vivo-like pattern formation and morphogenesis, though the processes controlling this are poorly characterized. While these in vitro self-organized tissues far exceed the microscopic and functional complexity obtained by current tissue engineering technologies, they are non-physiological in shape and size and have limited function and lifespan. Here, we discuss how engineering efforts for guiding stem-cell-based development at multiple stages can form the basis for the assembly of highly complex and rationally designed self-organizing multicellular systems with increased robustness and physiological relevance.
In response to severe injury to the skin or peripheral nerves, adult mammals typically undergo an irreversible repair process that results in contraction and the formation of non-physiologic scar tissue. However, recent advancements with induced regeneration using biologically active scaffolds have demonstrated that it is possible to intervene during the healing process to partially or near-completely restore the physiologic function of damaged skin or peripheral nerves. The aim of these scaffolds is to promote regeneration and minimize the contraction and scar formation mediated by stromal fibroblasts. For instance, some scaffolds appear to downregulate TGF-β signaling, a key inductor of myofibroblasts which promote contraction and scar formation. Two collagen-based and three synthetic-based regenerative devices have been approved by the Food and Drug Administration (FDA), two for the regeneration of the skin and three for the regeneration of peripheral nerves. Increasingly, these devices are establishing themselves as a viable alternative to autografting.
Regenerative medicine mainly relies on heterologous transplantation, often hindered by sample availability and ethical issues. Furthermore, patients are required to take immunosuppressive medications to prevent adverse side effects. Stem cell-derived 3D-organoid culture has provided new alternatives for transplantation and regenerative medicine. Scholars have combined organoids with tissue engineering technology to improve reproducibility, the accuracy of constitution and throughput, and genetic correction to achieve a more personalised therapy. Here, we review the available applications of organoids in regenerative medicine and the current challenges concerning this field.
