Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various diseases.While rapid progress has been made in regenerative medicine for spinal cord injury that was previou...Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various diseases.While rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete injury.However,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental importance.The reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural regeneration.Thus,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe pathologies.First,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further investigation.Here,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.展开更多
In this editorial,we comment on the hard and soft tissue applications of different ceramic-based scaffolds prepared by different mechanisms such as 3D printing,sol-gel,and electrospinning.The new concept of regenerati...In this editorial,we comment on the hard and soft tissue applications of different ceramic-based scaffolds prepared by different mechanisms such as 3D printing,sol-gel,and electrospinning.The new concept of regenerative medicine relies on biomaterials that can trigger in situ tissue regeneration and stem cell recruitment at the defect site.A large percentage of these biomaterials is ceramic-based as they provide the essential requirements of biomaterial principles such as tailored multisize porosity,antibacterial properties,and angiogenic properties.All these previously mentioned properties put bioceramics on top of the hierarchy of biomaterials utilized to stimulate tissue regeneration in soft and hard tissue wounds.Multiple clinical applications registered the use of these materials in triggering soft tissue regeneration in healthy and diabetic patients such as bioactive glass nanofibers.The results were promising and opened new frontiers for utilizing these materials on a larger scale.The same results were mentioned when using different forms and formulas of bioceramics in hard defect regeneration.Some bioceramics were used in combination with other polymers and biological scaffolds to improve their regenerative and mechanical properties.All this progress will enable a larger scale of patients to receive such services with ease and decrease the financial burden on the government.展开更多
Cell transplantation therapy has certain limitations including immune rejection and limited cell viability,which seriously hinder the transformation of stem cellbased tissue regeneration into clinical practice.Extrace...Cell transplantation therapy has certain limitations including immune rejection and limited cell viability,which seriously hinder the transformation of stem cellbased tissue regeneration into clinical practice.Extracellular vesicles(EVs)not only possess the advantages of its derived cells,but also can avoid the risks of cell transplantation.EVs are intelligent and controllable biomaterials that can participate in a variety of physiological and pathological activities,tissue repair and regeneration by transmitting a variety of biological signals,showing great potential in cell-free tissue regeneration.In this review,we summarized the origins and characteristics of EVs,introduced the pivotal role of EVs in diverse tissues regeneration,discussed the underlying mechanisms,prospects,and challenges of EVs.We also pointed out the problems that need to be solved,application directions,and prospects of EVs in the future and shed new light on the novel cell-free strategy for using EVs in the field of regenerative medicine.展开更多
The issue of skin defects is a major concern of almost every trauma surgeon after surgery. Despite numerous conventional methods and introduction of the reconstruction ladder, managing skin defects is still a challeng...The issue of skin defects is a major concern of almost every trauma surgeon after surgery. Despite numerous conventional methods and introduction of the reconstruction ladder, managing skin defects is still a challenge for the trauma surgeons. In recent years, parallel to the advances in the more conventional methods of skin repair, regenerative medicine has offered new and novel treatments. This article aims to explore these contemporary regenerative solutions as well as to review the conventional methods of treating skin defects.展开更多
Purpose: Despite many scientific advances, Regenerative Medicine is still in the preclinical stages in many areas. In this article, we intend to discuss the role of microsurgery in the bench-to-bedside transition of s...Purpose: Despite many scientific advances, Regenerative Medicine is still in the preclinical stages in many areas. In this article, we intend to discuss the role of microsurgery in the bench-to-bedside transition of such primary findings. Method: By searching the papers related to the history of Regenerative Medicine (RM) and the news of Tissue Engineering (TE) in orthopedics in Pubmed, Scopus, and Google Scholar databases, we accessed a complete archive of various topics related to this field. Result: We first assessed the history and achievements of regenerative medicine, then we realized the importance of translational medical sciences and the role of animal models in this incipient phenomenon. Finally, after mastering the capabilities of microsurgery and the useful contribution of this technique to the advancement of clinical applications of regenerative medicine in various branches such as skin, skeletal system, nerves, and blood vessels, we decided to express the gist of our studies through this article. Conclusion: Considering the widespread use of small animals in regenerative medicine projects and the inevitable role of microsurgery in performing the best intervention on these animal models, the significant progress of regenerative medicine clinical application requires special attention to microsurgery in associated research.展开更多
Mesenchymal stem cells(MSCs)are multipotent stem cells with marked potential for regenerative medicine because of their strong immunosuppressive and regenerative abilities.The therapeutic effects of MSCs are based in ...Mesenchymal stem cells(MSCs)are multipotent stem cells with marked potential for regenerative medicine because of their strong immunosuppressive and regenerative abilities.The therapeutic effects of MSCs are based in part on their secretion of biologically active factors in extracellular vesicles known as exosomes.Exosomes have a diameter of 30-100 nm and mediate intercellular communication and material exchange.MSC-derived exosomes(MSC-Exos)have potential for cell-free therapy for diseases of,for instance,the kidney,liver,heart,nervous system,and musculoskeletal system.Hence,MSC-Exos are an alternative to MSCbased therapy for regenerative medicine.We review MSC-Exos and their therapeutic potential for a variety of diseases and injuries.展开更多
Regenerative medicine(RM) is an emerging interdisciplinary field of research and China has developed the research quickly and impressed the world with numerous research findings in stem cells,tissue engineering,active...Regenerative medicine(RM) is an emerging interdisciplinary field of research and China has developed the research quickly and impressed the world with numerous research findings in stem cells,tissue engineering,active molecules and gene therapy.Important directions are induced differentiation of induced pluripotent stem and embryo stem cells as well as somatic stem cell differentiation potential and their application in trauma,burns,diseases of aging and nerve regeneration.The products Activ Skin and bone repair scaffolds have been approved and are applied in the clinic,and similar products are being studied.About 10 engineered growth-factor drugs for repair and regeneration have been approved and are used in the clinic.Gene therapy,therapeutic cloning and xenotransplantation are some of the strategies being studied.However,China needs to develop standards,regulations and management practices suitable for the healthy development of RM.Aspects that should be strengthened include sound administrative systems,laws,and technical specifications and guidelines;conservation of stem cell resources;emphasis on training and retention of talented stem cell researchers;and reasonable allocation of resources,diversification of investment and breakthroughs in key areas.Finally,broad and deep international cooperation is necessary.展开更多
An appropriate cell microenvironment is key to tissue engineering and regenerative medicine.Revealing the factors that influence the cell microenvironment is a fundamental research topic in the fields of cell biology,...An appropriate cell microenvironment is key to tissue engineering and regenerative medicine.Revealing the factors that influence the cell microenvironment is a fundamental research topic in the fields of cell biology,biomaterials,tissue engineering,and regenerative medicine.The cell microenvironment consists of not only its surrounding cells and soluble factors,but also its extracellular matrix(ECM)or nearby external biomaterials in tissue engineering and regeneration.This review focuses on six aspects of bioma-terial-related cell microenvironments:①chemical composition of materials,②material dimensions and architecture,③material-controlled cell geometry,④effects of material charges on cells,⑤matrix stiff-ness and biomechanical microenvironment,and⑥surface modification of materials.The present chal-lenges in tissue engineering are also mentioned,and eight perspectives are predicted.展开更多
Of late, the relevance of silk in a myriad of material science and biotechnological realms has been realized, as attested by the incessantly clambering number of reports and patents in the scienti fic repositories. Th...Of late, the relevance of silk in a myriad of material science and biotechnological realms has been realized, as attested by the incessantly clambering number of reports and patents in the scienti fic repositories. The write-up is geared off with a scrutiny into the pertinence of the basic nano-structural features of silk, christened as the ‘queen of textile’ for exemplary bioengi- neering applications including designing and fabrication of devices for micro fluidics, opto fluidics, chemo/bio sensing, etc. Then, the major thrust of this short review is directed towards comprehending the prospects of using silk-based biomaterials (e.g. sca ffolds, electrospun membranes, films, hydrogels, bioinks) for tissue engineering and regenerative medicine as well as targeted delivery of various biomolecular cargoes/therapeutic agents, etc., as vouched by few avant-garde endeavours of the recent years. The write-up is entwined with a discussion on the various factors that could plausibly hinder the realization of silk as the next-generation nanobiomaterial, suggestions for some approaches to dodge and deal with the practical snags and what lies ahead!展开更多
Adipose tissue is a compact and well-organized tissue containing a heterogeneous cellular population of progenitor cells,including mesenchymal stromal cells.Due to its availability and accessibility,adipose tissue is ...Adipose tissue is a compact and well-organized tissue containing a heterogeneous cellular population of progenitor cells,including mesenchymal stromal cells.Due to its availability and accessibility,adipose tissue is considered a“stem cell depot.”Adipose tissue products possess anti-inflammatory,anti-fibrotic,antiapoptotic,and immunomodulatory effects.Nanofat,being a compact bundle of stem cells with regenerative and tissue remodeling potential,has potential in translational and regenerative medicine.Considering the wide range of applicability of its reconstructive and regenerative potential,the applications of nanofat can be used in various disciplines.Nanofat behaves on the line of adipose tissuederived mesenchymal stromal cells.At the site of injury,these stromal cells initiate a site-specific reparative response comprised of remodeling of the extracellular matrix,enhanced and sustained angiogenesis,and immune system modulation.These properties of stromal cells provide a platform for the usage of regenerative medicine principles in curbing various diseases.Details about nanofat,including various preparation methods,characterization,delivery methods,evidence on practical applications,and ethical concerns are included in this review.However,appropriate guidelines and preparation protocols for its optimal use in a wide range of clinical applications have yet to be standardized.展开更多
This article presents the stem and progenitor cells from subcutaneous adipose tissue,briefly comparing them with their bone marrow counterparts,and discussing their potential for use in regenerative medicine.Subcutane...This article presents the stem and progenitor cells from subcutaneous adipose tissue,briefly comparing them with their bone marrow counterparts,and discussing their potential for use in regenerative medicine.Subcutaneous adipose tissue differs from other mesenchymal stromal/stem cells(MSCs)sources in that it contains a pre-adipocyte population that dwells in the adventitia of robust blood vessels.Pre-adipocytes are present both in the stromal-vascular fraction(SVF;freshly isolated cells)and in the adherent fraction of adipose stromal/stem cells(ASCs;in vitro expanded cells),and have an active role on the chronic inflammation environment established in obesity,likely due their monocyticmacrophage lineage identity.The SVF and ASCs have been explored in cell therapy protocols with relative success,given their paracrine and immunomodulatory effects.Importantly,the widely explored multipotentiality of ASCs has direct application in bone,cartilage and adipose tissue engineering.The aim of this editorial is to reinforce the peculiarities of the stem and progenitor cells from subcutaneous adipose tissue,revealing the spheroids as a recently described biotechnological tool for cell therapy and tissue engineering.Innovative cell culture techniques,in particular 3D scaffold-free cultures such as spheroids,are now available to increase the potential for regeneration and differentiation of mesenchymal lineages.Spheroids are being explored not only as a model for cell differentiation,but also as powerful 3D cell culture tools to maintain the stemness and expand the regenerative and differentiation capacities of mesenchymal cell lineages.展开更多
The human teeth and oral cavity harbor various populations of mesenchymal stem cells(MSCs),so called dental-derived stem cells(D-dSCs)with self-renewing and multilineage differentiation capabilities.D-dSCs properties ...The human teeth and oral cavity harbor various populations of mesenchymal stem cells(MSCs),so called dental-derived stem cells(D-dSCs)with self-renewing and multilineage differentiation capabilities.D-dSCs properties involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment.Altogether,this viewpoint develops a general picture of current innovative strategies to employ D-dSCs combined with biomaterials and bioactive factors for regenerative medicine purposes,and offers information regarding the available scientific data and possible applications.展开更多
Mesenchymal stem cells(MSCs)represent the most clinically used stem cells in regenerative medicine.However,due to the disadvantages with primary MSCs,such as limited cell proliferative capacity and rarity in the tissu...Mesenchymal stem cells(MSCs)represent the most clinically used stem cells in regenerative medicine.However,due to the disadvantages with primary MSCs,such as limited cell proliferative capacity and rarity in the tissues leading to limited MSCs,gradual loss of differentiation during in vitro expansion reducing the efficacy of MSC application,and variation among donors increasing the uncertainty of MSC efficacy,the clinical application of MSCs has been greatly hampered.MSCs derived from human pluripotent stem cells(hPSC-MSCs)can circumvent these problems associated with primary MSCs.Due to the infinite selfrenewal of hPSCs and their differentiation potential towards MSCs,hPSC-MSCs are emerging as an attractive alternative for regenerative medicine.This review summarizes the progress on derivation of MSCs from human pluripotent stem cells,disease modelling and drug screening using hPSC-MSCs,and various applications of hPSC-MSCs in regenerative medicine.In the end,the challenges and concerns with hPSC-MSC applications are also discussed.展开更多
Stem cells hold indefinite self-renewable capability that can be differentiated into all desired cell types.Based on their plasticity potential,they are divided into totipotent(morula stage cells),pluripotent(embryoni...Stem cells hold indefinite self-renewable capability that can be differentiated into all desired cell types.Based on their plasticity potential,they are divided into totipotent(morula stage cells),pluripotent(embryonic stem cells),multipotent(hematopoietic stem cells,multipotent adult progenitor stem cells,and mesenchymal stem cells[MSCs]),and unipotent(progenitor cells that differentiate into a single lineage)cells.Though bone marrow is the primary source of multipotent stem cells in adults,other tissues such as adipose tissues,placenta,amniotic fluid,umbilical cord blood,periodontal ligament,and dental pulp also harbor stem cells that can be used for regenerative therapy.In addition,induced pluripotent stem cells also exhibit fundamental properties of self-renewal and differentiation into specialized cells,and thus could be another source for regenerative medicine.Several diseases including neurodegenerative diseases,cardiovascular diseases,autoimmune diseases,virus infection(also coronavirus disease 2019)have limited success with conventional medicine,and stem cell transplantation is assumed to be the best therapy to treat these disorders.Importantly,MSCs,are by far the best for regenerative medicine due to their limited immune modulation and adequate tissue repair.Moreover,MSCs have the potential to migrate towards the damaged area,which is regulated by various factors and signaling processes.Recent studies have shown that extracellular calcium(Ca^(2+))promotes the proliferation of MSCs,and thus can assist in transplantation therapy.Ca^(2+)signaling is a highly adaptable intracellular signal that contains several components such as cell-surface receptors,Ca^(2+)channels/pumps/exchangers,Ca^(2+)buffers,and Ca^(2+)sensors,which together are essential for the appropriate functioning of stem cells and thus modulate their proliferative and regenerative capacity,which will be discussed in this review.展开更多
Surgery, chemotherapy and radiotherapy are the gold standard treatments</span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"...Surgery, chemotherapy and radiotherapy are the gold standard treatments</span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> used for cancer. Side effects from medical radiation can be significant, particularly external beam therapy to the breast, and head and neck regions causing </span><span style="font-family:Verdana;">fibrosis, secondary skin cancer, hair loss, oral mucositis and neuropathic</span><span style="font-family:Verdana;"> pain. There is significant psychological stress, depression, anxiety and loss of self esteem particularly for female patients. Similar types of space radiation are known to damage the health of astronauts. Current treatments for scarring, tissue loss, hair loss and neuropathic pain are a high priority but inadequate. Regenerative medicine is a new and comprehensive approach to potentially treat complex medical conditions from radiation damage. Regenerative medicine combines a systematic evidence based approach with the use of herbal medicine, stem cells, peptides and 3D tissue engineering. These fields use sophisticated technology to identify the respective molecular mechanisms of upregulation and protection of healthy cells and down regulation of cancer cells. The regenerative medicine strategies of stem cells and plant polyphenols suggest there is significant potential for rapid clinical translation to alleviate the side effects associated with radiotherapy.展开更多
AIM To establish a hypoxic environment for promoting osteogenesis in rat marrow stromal cells(MSCs) using osteogenic matrix cell sheets(OMCSs).METHODS Rat MSCs were cultured in osteogenic media under one of four varyi...AIM To establish a hypoxic environment for promoting osteogenesis in rat marrow stromal cells(MSCs) using osteogenic matrix cell sheets(OMCSs).METHODS Rat MSCs were cultured in osteogenic media under one of four varying oxygen conditions: Normoxia(21% O_2) for 14 d(NN), normoxia for 7 d followed by hypoxia(5% O_2) for 7 d(NH), hypoxia for 7 d followed by normoxia for 7 d(HN), or hypoxia for 14 d(HH). Osteogenesis was evaluated by observing changes in cell morphology and calcium deposition, and by measuring osteocalcin secretion(ELISA) and calcium content. In vivo syngeneic transplantation using OMCSs and β-tricalcium phosphate discs, preconditioned under NN or HN conditions, was also evaluated by histology, calcium content measurements,and real-time quantitative PCR.RESULTS In the NN and HN groups, differentiated, cuboidal-shaped cells were readily observed, along with calcium deposits. In the HN group, the levels of secreted osteocalcin increased rapidly from day 10 as compared with the other groups, and plateaued at day 12(P < 0.05). At day 14, the HN group showed the highest amount of calcium deposition. In vivo, the HN group showed histologically prominent new bone formation, increased calcium deposition, and higher collagen type Ⅰ?messenger RNA expression as compared with the NN group.CONCLUSION The results of this study indicate that modifying oxygen tension is an effective method to enhance the osteogenic ability of MSCs used for OMCSs.展开更多
Mesenchymal stem cells(MSCs)play key roles in regenerative medicine by promoting tissue healing.MSCs can be isolated from different adult tissues and they are able to differentiate into several lineages.Due to their a...Mesenchymal stem cells(MSCs)play key roles in regenerative medicine by promoting tissue healing.MSCs can be isolated from different adult tissues and they are able to differentiate into several lineages.Due to their antiinflammatory,angiogenic and immune-modulatory properties,MSCs are suitable for tissue engineering applications and,when associated with biomaterials,their benefits can be improved.Moreover,recently,MSCs have been studied for new clinical applications,such as in the treatment of patients with COVID-19.MSCs regenerative potential has been attributed to their secretome,which comprises extracellular matrix,soluble proteins and several elements,including the release of extracellular vesicles.Even though,in order to explore all their therapeutic potential,it is still necessary to advance in the investigation of their basic cell biology characteristics.展开更多
Stem cells are undifferentiated cells that can self-renew and differentiate into diverse types of mature and functional cells while maintaining their original identity.This profound potential of stem cells has been th...Stem cells are undifferentiated cells that can self-renew and differentiate into diverse types of mature and functional cells while maintaining their original identity.This profound potential of stem cells has been thoroughly investigated for its significance in regenerative medicine and has laid the foundation for cellbased therapies.Regenerative medicine is rapidly progressing in healthcare with the prospect of repair and restoration of specific organs or tissue injuries or chronic disease conditions where the body’s regenerative process is not sufficient to heal.In this review,the recent advances in stem cell-based therapies in regenerative medicine are discussed,emphasizing mesenchymal stem cell-based therapies as these cells have been extensively studied for clinical use.Recent applications of artificial intelligence algorithms in stem cell-based therapies,their limitation,and future prospects are highlighted.展开更多
Mesenchymal stem cells(MSCs)are multipotent cells usually isolated from bone marrow,endometrium,adipose tissues,skin,and dental pulp.MSCs played a crucial role in regenerative therapy and have been introduced as an in...Mesenchymal stem cells(MSCs)are multipotent cells usually isolated from bone marrow,endometrium,adipose tissues,skin,and dental pulp.MSCs played a crucial role in regenerative therapy and have been introduced as an interdisciplinary field between cell biology and material science.Recently,MSCs have been widely explored for their application in regenerative medicine and COVID-19 treatment.Different approaches to evaluate the future of biomaterials and stem cell properties have been developed.However,misconceptions and ethical issues still exist,such as MSCs being non-angiogenic,anti-apoptotic,and immunoregulatory competencies.Embryonic stem cells isolation primarily requires the consent of donors and can include the killing of fertilized eggs.These issues generate questions related to ethical and moral issues.However,MSCs have gained considerable attention for tissue regeneration owing to their differentiation ability with immunomodulatory effects.They are capable of secreting a broad range of biomolecules such as proteins,nucleic acids,exosomes,microRNAs,and membrane vesicles,collectively known as secretomes.Secretomes are released in response to the surrounding microenvironment.In this article,we briefly address topics related to the therapeutic potential of MSCs as an advanced approach in the field of regenerative medicine and various perspectives.展开更多
Advances in regenerative medicine correlate strongly with progress in the use of adipose tissue-derived mesenchymal stem/stromal cells.The range of therapeutic indications has also expanded over recent years.Numerous ...Advances in regenerative medicine correlate strongly with progress in the use of adipose tissue-derived mesenchymal stem/stromal cells.The range of therapeutic indications has also expanded over recent years.Numerous recent studies have highlighted the primary importance of paracrine secretion by these cells.Though it is interesting to compare the different types of such secretions,we believe that exosomes(extra-cellular vesicles possessing the same properties as their source cells)will likely be the main key in tomorrow’s cell therapy.Exosomes also have many advantages compared to the direct use of cells,making these particles amajor target in fundamental and translational research.展开更多
文摘Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various diseases.While rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete injury.However,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental importance.The reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural regeneration.Thus,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe pathologies.First,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further investigation.Here,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.
文摘In this editorial,we comment on the hard and soft tissue applications of different ceramic-based scaffolds prepared by different mechanisms such as 3D printing,sol-gel,and electrospinning.The new concept of regenerative medicine relies on biomaterials that can trigger in situ tissue regeneration and stem cell recruitment at the defect site.A large percentage of these biomaterials is ceramic-based as they provide the essential requirements of biomaterial principles such as tailored multisize porosity,antibacterial properties,and angiogenic properties.All these previously mentioned properties put bioceramics on top of the hierarchy of biomaterials utilized to stimulate tissue regeneration in soft and hard tissue wounds.Multiple clinical applications registered the use of these materials in triggering soft tissue regeneration in healthy and diabetic patients such as bioactive glass nanofibers.The results were promising and opened new frontiers for utilizing these materials on a larger scale.The same results were mentioned when using different forms and formulas of bioceramics in hard defect regeneration.Some bioceramics were used in combination with other polymers and biological scaffolds to improve their regenerative and mechanical properties.All this progress will enable a larger scale of patients to receive such services with ease and decrease the financial burden on the government.
基金Supported by The Interdisciplinary and Intercollege Research Project of the State Key Laboratory of Oral Disease,Sichuan University,No.2021KXK0403Health Commission of Sichuan Province,No.21PJ062。
文摘Cell transplantation therapy has certain limitations including immune rejection and limited cell viability,which seriously hinder the transformation of stem cellbased tissue regeneration into clinical practice.Extracellular vesicles(EVs)not only possess the advantages of its derived cells,but also can avoid the risks of cell transplantation.EVs are intelligent and controllable biomaterials that can participate in a variety of physiological and pathological activities,tissue repair and regeneration by transmitting a variety of biological signals,showing great potential in cell-free tissue regeneration.In this review,we summarized the origins and characteristics of EVs,introduced the pivotal role of EVs in diverse tissues regeneration,discussed the underlying mechanisms,prospects,and challenges of EVs.We also pointed out the problems that need to be solved,application directions,and prospects of EVs in the future and shed new light on the novel cell-free strategy for using EVs in the field of regenerative medicine.
文摘The issue of skin defects is a major concern of almost every trauma surgeon after surgery. Despite numerous conventional methods and introduction of the reconstruction ladder, managing skin defects is still a challenge for the trauma surgeons. In recent years, parallel to the advances in the more conventional methods of skin repair, regenerative medicine has offered new and novel treatments. This article aims to explore these contemporary regenerative solutions as well as to review the conventional methods of treating skin defects.
文摘Purpose: Despite many scientific advances, Regenerative Medicine is still in the preclinical stages in many areas. In this article, we intend to discuss the role of microsurgery in the bench-to-bedside transition of such primary findings. Method: By searching the papers related to the history of Regenerative Medicine (RM) and the news of Tissue Engineering (TE) in orthopedics in Pubmed, Scopus, and Google Scholar databases, we accessed a complete archive of various topics related to this field. Result: We first assessed the history and achievements of regenerative medicine, then we realized the importance of translational medical sciences and the role of animal models in this incipient phenomenon. Finally, after mastering the capabilities of microsurgery and the useful contribution of this technique to the advancement of clinical applications of regenerative medicine in various branches such as skin, skeletal system, nerves, and blood vessels, we decided to express the gist of our studies through this article. Conclusion: Considering the widespread use of small animals in regenerative medicine projects and the inevitable role of microsurgery in performing the best intervention on these animal models, the significant progress of regenerative medicine clinical application requires special attention to microsurgery in associated research.
文摘Mesenchymal stem cells(MSCs)are multipotent stem cells with marked potential for regenerative medicine because of their strong immunosuppressive and regenerative abilities.The therapeutic effects of MSCs are based in part on their secretion of biologically active factors in extracellular vesicles known as exosomes.Exosomes have a diameter of 30-100 nm and mediate intercellular communication and material exchange.MSC-derived exosomes(MSC-Exos)have potential for cell-free therapy for diseases of,for instance,the kidney,liver,heart,nervous system,and musculoskeletal system.Hence,MSC-Exos are an alternative to MSCbased therapy for regenerative medicine.We review MSC-Exos and their therapeutic potential for a variety of diseases and injuries.
基金supported by the National Nature Science Foundation of China(81171812,81272105,81121004,81230041,and 81171798)the National Basic Science and Development Programme(973 Programme,2012CB518105)+2 种基金the National Science and Technology Major Project(2011ZXJ07104B-03B)the Health and Medical Treatment Collaborative Innovation Major Special Projects of Guangzhou(No.201508020253)the Science and Technology Key Project of Guangdong Province(2014B020212010)
文摘Regenerative medicine(RM) is an emerging interdisciplinary field of research and China has developed the research quickly and impressed the world with numerous research findings in stem cells,tissue engineering,active molecules and gene therapy.Important directions are induced differentiation of induced pluripotent stem and embryo stem cells as well as somatic stem cell differentiation potential and their application in trauma,burns,diseases of aging and nerve regeneration.The products Activ Skin and bone repair scaffolds have been approved and are applied in the clinic,and similar products are being studied.About 10 engineered growth-factor drugs for repair and regeneration have been approved and are used in the clinic.Gene therapy,therapeutic cloning and xenotransplantation are some of the strategies being studied.However,China needs to develop standards,regulations and management practices suitable for the healthy development of RM.Aspects that should be strengthened include sound administrative systems,laws,and technical specifications and guidelines;conservation of stem cell resources;emphasis on training and retention of talented stem cell researchers;and reasonable allocation of resources,diversification of investment and breakthroughs in key areas.Finally,broad and deep international cooperation is necessary.
基金the financial support from the National Natural Science Foundation of China (21961160721 and 52130302)the National Key Research and Development Program of China(2016YFC1100300)
文摘An appropriate cell microenvironment is key to tissue engineering and regenerative medicine.Revealing the factors that influence the cell microenvironment is a fundamental research topic in the fields of cell biology,biomaterials,tissue engineering,and regenerative medicine.The cell microenvironment consists of not only its surrounding cells and soluble factors,but also its extracellular matrix(ECM)or nearby external biomaterials in tissue engineering and regeneration.This review focuses on six aspects of bioma-terial-related cell microenvironments:①chemical composition of materials,②material dimensions and architecture,③material-controlled cell geometry,④effects of material charges on cells,⑤matrix stiff-ness and biomechanical microenvironment,and⑥surface modification of materials.The present chal-lenges in tissue engineering are also mentioned,and eight perspectives are predicted.
文摘Of late, the relevance of silk in a myriad of material science and biotechnological realms has been realized, as attested by the incessantly clambering number of reports and patents in the scienti fic repositories. The write-up is geared off with a scrutiny into the pertinence of the basic nano-structural features of silk, christened as the ‘queen of textile’ for exemplary bioengi- neering applications including designing and fabrication of devices for micro fluidics, opto fluidics, chemo/bio sensing, etc. Then, the major thrust of this short review is directed towards comprehending the prospects of using silk-based biomaterials (e.g. sca ffolds, electrospun membranes, films, hydrogels, bioinks) for tissue engineering and regenerative medicine as well as targeted delivery of various biomolecular cargoes/therapeutic agents, etc., as vouched by few avant-garde endeavours of the recent years. The write-up is entwined with a discussion on the various factors that could plausibly hinder the realization of silk as the next-generation nanobiomaterial, suggestions for some approaches to dodge and deal with the practical snags and what lies ahead!
文摘Adipose tissue is a compact and well-organized tissue containing a heterogeneous cellular population of progenitor cells,including mesenchymal stromal cells.Due to its availability and accessibility,adipose tissue is considered a“stem cell depot.”Adipose tissue products possess anti-inflammatory,anti-fibrotic,antiapoptotic,and immunomodulatory effects.Nanofat,being a compact bundle of stem cells with regenerative and tissue remodeling potential,has potential in translational and regenerative medicine.Considering the wide range of applicability of its reconstructive and regenerative potential,the applications of nanofat can be used in various disciplines.Nanofat behaves on the line of adipose tissuederived mesenchymal stromal cells.At the site of injury,these stromal cells initiate a site-specific reparative response comprised of remodeling of the extracellular matrix,enhanced and sustained angiogenesis,and immune system modulation.These properties of stromal cells provide a platform for the usage of regenerative medicine principles in curbing various diseases.Details about nanofat,including various preparation methods,characterization,delivery methods,evidence on practical applications,and ethical concerns are included in this review.However,appropriate guidelines and preparation protocols for its optimal use in a wide range of clinical applications have yet to be standardized.
基金Supported by the Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro(FAPERJ),No.E-26/202.682/2018
文摘This article presents the stem and progenitor cells from subcutaneous adipose tissue,briefly comparing them with their bone marrow counterparts,and discussing their potential for use in regenerative medicine.Subcutaneous adipose tissue differs from other mesenchymal stromal/stem cells(MSCs)sources in that it contains a pre-adipocyte population that dwells in the adventitia of robust blood vessels.Pre-adipocytes are present both in the stromal-vascular fraction(SVF;freshly isolated cells)and in the adherent fraction of adipose stromal/stem cells(ASCs;in vitro expanded cells),and have an active role on the chronic inflammation environment established in obesity,likely due their monocyticmacrophage lineage identity.The SVF and ASCs have been explored in cell therapy protocols with relative success,given their paracrine and immunomodulatory effects.Importantly,the widely explored multipotentiality of ASCs has direct application in bone,cartilage and adipose tissue engineering.The aim of this editorial is to reinforce the peculiarities of the stem and progenitor cells from subcutaneous adipose tissue,revealing the spheroids as a recently described biotechnological tool for cell therapy and tissue engineering.Innovative cell culture techniques,in particular 3D scaffold-free cultures such as spheroids,are now available to increase the potential for regeneration and differentiation of mesenchymal lineages.Spheroids are being explored not only as a model for cell differentiation,but also as powerful 3D cell culture tools to maintain the stemness and expand the regenerative and differentiation capacities of mesenchymal cell lineages.
文摘The human teeth and oral cavity harbor various populations of mesenchymal stem cells(MSCs),so called dental-derived stem cells(D-dSCs)with self-renewing and multilineage differentiation capabilities.D-dSCs properties involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment.Altogether,this viewpoint develops a general picture of current innovative strategies to employ D-dSCs combined with biomaterials and bioactive factors for regenerative medicine purposes,and offers information regarding the available scientific data and possible applications.
文摘Mesenchymal stem cells(MSCs)represent the most clinically used stem cells in regenerative medicine.However,due to the disadvantages with primary MSCs,such as limited cell proliferative capacity and rarity in the tissues leading to limited MSCs,gradual loss of differentiation during in vitro expansion reducing the efficacy of MSC application,and variation among donors increasing the uncertainty of MSC efficacy,the clinical application of MSCs has been greatly hampered.MSCs derived from human pluripotent stem cells(hPSC-MSCs)can circumvent these problems associated with primary MSCs.Due to the infinite selfrenewal of hPSCs and their differentiation potential towards MSCs,hPSC-MSCs are emerging as an attractive alternative for regenerative medicine.This review summarizes the progress on derivation of MSCs from human pluripotent stem cells,disease modelling and drug screening using hPSC-MSCs,and various applications of hPSC-MSCs in regenerative medicine.In the end,the challenges and concerns with hPSC-MSC applications are also discussed.
基金National Institute of Dental&Craniofacial Research,No.1R21DE028265-01A1.
文摘Stem cells hold indefinite self-renewable capability that can be differentiated into all desired cell types.Based on their plasticity potential,they are divided into totipotent(morula stage cells),pluripotent(embryonic stem cells),multipotent(hematopoietic stem cells,multipotent adult progenitor stem cells,and mesenchymal stem cells[MSCs]),and unipotent(progenitor cells that differentiate into a single lineage)cells.Though bone marrow is the primary source of multipotent stem cells in adults,other tissues such as adipose tissues,placenta,amniotic fluid,umbilical cord blood,periodontal ligament,and dental pulp also harbor stem cells that can be used for regenerative therapy.In addition,induced pluripotent stem cells also exhibit fundamental properties of self-renewal and differentiation into specialized cells,and thus could be another source for regenerative medicine.Several diseases including neurodegenerative diseases,cardiovascular diseases,autoimmune diseases,virus infection(also coronavirus disease 2019)have limited success with conventional medicine,and stem cell transplantation is assumed to be the best therapy to treat these disorders.Importantly,MSCs,are by far the best for regenerative medicine due to their limited immune modulation and adequate tissue repair.Moreover,MSCs have the potential to migrate towards the damaged area,which is regulated by various factors and signaling processes.Recent studies have shown that extracellular calcium(Ca^(2+))promotes the proliferation of MSCs,and thus can assist in transplantation therapy.Ca^(2+)signaling is a highly adaptable intracellular signal that contains several components such as cell-surface receptors,Ca^(2+)channels/pumps/exchangers,Ca^(2+)buffers,and Ca^(2+)sensors,which together are essential for the appropriate functioning of stem cells and thus modulate their proliferative and regenerative capacity,which will be discussed in this review.
文摘Surgery, chemotherapy and radiotherapy are the gold standard treatments</span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> used for cancer. Side effects from medical radiation can be significant, particularly external beam therapy to the breast, and head and neck regions causing </span><span style="font-family:Verdana;">fibrosis, secondary skin cancer, hair loss, oral mucositis and neuropathic</span><span style="font-family:Verdana;"> pain. There is significant psychological stress, depression, anxiety and loss of self esteem particularly for female patients. Similar types of space radiation are known to damage the health of astronauts. Current treatments for scarring, tissue loss, hair loss and neuropathic pain are a high priority but inadequate. Regenerative medicine is a new and comprehensive approach to potentially treat complex medical conditions from radiation damage. Regenerative medicine combines a systematic evidence based approach with the use of herbal medicine, stem cells, peptides and 3D tissue engineering. These fields use sophisticated technology to identify the respective molecular mechanisms of upregulation and protection of healthy cells and down regulation of cancer cells. The regenerative medicine strategies of stem cells and plant polyphenols suggest there is significant potential for rapid clinical translation to alleviate the side effects associated with radiotherapy.
文摘AIM To establish a hypoxic environment for promoting osteogenesis in rat marrow stromal cells(MSCs) using osteogenic matrix cell sheets(OMCSs).METHODS Rat MSCs were cultured in osteogenic media under one of four varying oxygen conditions: Normoxia(21% O_2) for 14 d(NN), normoxia for 7 d followed by hypoxia(5% O_2) for 7 d(NH), hypoxia for 7 d followed by normoxia for 7 d(HN), or hypoxia for 14 d(HH). Osteogenesis was evaluated by observing changes in cell morphology and calcium deposition, and by measuring osteocalcin secretion(ELISA) and calcium content. In vivo syngeneic transplantation using OMCSs and β-tricalcium phosphate discs, preconditioned under NN or HN conditions, was also evaluated by histology, calcium content measurements,and real-time quantitative PCR.RESULTS In the NN and HN groups, differentiated, cuboidal-shaped cells were readily observed, along with calcium deposits. In the HN group, the levels of secreted osteocalcin increased rapidly from day 10 as compared with the other groups, and plateaued at day 12(P < 0.05). At day 14, the HN group showed the highest amount of calcium deposition. In vivo, the HN group showed histologically prominent new bone formation, increased calcium deposition, and higher collagen type Ⅰ?messenger RNA expression as compared with the NN group.CONCLUSION The results of this study indicate that modifying oxygen tension is an effective method to enhance the osteogenic ability of MSCs used for OMCSs.
基金This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil(CAPES)-Finance Code 001TCP is fellowship from PhD CAPES(Coordenação de Aperfeiçoamento de Pessoal de Nível Superior)+3 种基金MRW is recipient of 1D level research fellowship from CNPq(Conselho Nacional de Desenvolvimento Científico e Tecnológico)This study was supported by CNPq,MS-SCTIE-Decit/CNPq no 12/2018(441575/2018-8)MSSCTIE-DECIT-DGITIS-CGCIS/CNPq no 26/2020(442586/2020-5)by Fundação de AmparoàPesquisa do Estado do Rio Grande do Sul-Brasil(FAPERGS/CAPES 06/2018-Programa de Internacionalização da pós-graduação no RS(19/2551-0000679-9).
文摘Mesenchymal stem cells(MSCs)play key roles in regenerative medicine by promoting tissue healing.MSCs can be isolated from different adult tissues and they are able to differentiate into several lineages.Due to their antiinflammatory,angiogenic and immune-modulatory properties,MSCs are suitable for tissue engineering applications and,when associated with biomaterials,their benefits can be improved.Moreover,recently,MSCs have been studied for new clinical applications,such as in the treatment of patients with COVID-19.MSCs regenerative potential has been attributed to their secretome,which comprises extracellular matrix,soluble proteins and several elements,including the release of extracellular vesicles.Even though,in order to explore all their therapeutic potential,it is still necessary to advance in the investigation of their basic cell biology characteristics.
文摘Stem cells are undifferentiated cells that can self-renew and differentiate into diverse types of mature and functional cells while maintaining their original identity.This profound potential of stem cells has been thoroughly investigated for its significance in regenerative medicine and has laid the foundation for cellbased therapies.Regenerative medicine is rapidly progressing in healthcare with the prospect of repair and restoration of specific organs or tissue injuries or chronic disease conditions where the body’s regenerative process is not sufficient to heal.In this review,the recent advances in stem cell-based therapies in regenerative medicine are discussed,emphasizing mesenchymal stem cell-based therapies as these cells have been extensively studied for clinical use.Recent applications of artificial intelligence algorithms in stem cell-based therapies,their limitation,and future prospects are highlighted.
基金This research was supported by the Basic Research Program through the National Research Foundation of Korea(NRF),funded by the Ministry of Education(NRF-2018R1A6A1A03025582)the National Research Foundation of Korea(NRF-2019R1D1A3A03103828).
文摘Mesenchymal stem cells(MSCs)are multipotent cells usually isolated from bone marrow,endometrium,adipose tissues,skin,and dental pulp.MSCs played a crucial role in regenerative therapy and have been introduced as an interdisciplinary field between cell biology and material science.Recently,MSCs have been widely explored for their application in regenerative medicine and COVID-19 treatment.Different approaches to evaluate the future of biomaterials and stem cell properties have been developed.However,misconceptions and ethical issues still exist,such as MSCs being non-angiogenic,anti-apoptotic,and immunoregulatory competencies.Embryonic stem cells isolation primarily requires the consent of donors and can include the killing of fertilized eggs.These issues generate questions related to ethical and moral issues.However,MSCs have gained considerable attention for tissue regeneration owing to their differentiation ability with immunomodulatory effects.They are capable of secreting a broad range of biomolecules such as proteins,nucleic acids,exosomes,microRNAs,and membrane vesicles,collectively known as secretomes.Secretomes are released in response to the surrounding microenvironment.In this article,we briefly address topics related to the therapeutic potential of MSCs as an advanced approach in the field of regenerative medicine and various perspectives.
文摘Advances in regenerative medicine correlate strongly with progress in the use of adipose tissue-derived mesenchymal stem/stromal cells.The range of therapeutic indications has also expanded over recent years.Numerous recent studies have highlighted the primary importance of paracrine secretion by these cells.Though it is interesting to compare the different types of such secretions,we believe that exosomes(extra-cellular vesicles possessing the same properties as their source cells)will likely be the main key in tomorrow’s cell therapy.Exosomes also have many advantages compared to the direct use of cells,making these particles amajor target in fundamental and translational research.
