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1.
Rev Med Chil ; 147(6): 787-789, 2019 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-31859832

RESUMO

Heart failure is one of the first diseases in which stem cells were used for regenerative medicine. Since 2001, many publications have shown that stem cell therapy has the potential to mitigate heart diseases, but there is no solid scientific evidence to fully support its clinical application at present. The future of regenerative medicine requires validated clinical trials with standardized platforms and transdisciplinary efforts to enable the development of safe and effective regenerative therapies to protect patients and to promote the ethical application of this new and highly promising therapy. Doctors and scientists have a responsibility to discuss with patients the current reality of regenerative therapies. They also have a responsibility to discourage the indiscriminate and commercial use of these therapies, which are sometimes based on false hopes, since their inappropriate use can harm vulnerable patients as well as research efforts. Although regenerative medicine may be the medicine of the future and might bring the hope of cure for chronic diseases, it is not yet ready for its wide clinical application.


Assuntos
Insuficiência Cardíaca/terapia , Transplante de Células-Tronco/ética , Humanos , Medicina Regenerativa/ética , Medicina Regenerativa/tendências , Transplante de Células-Tronco/tendências
2.
Zhonghua Shao Shang Za Zhi ; 35(11): 828-832, 2019 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-31775475

RESUMO

The repair strategy after organs injuries has always been a hot topic in the field of regenerative medicine. Traditional injury repair measures mainly promote tissue repair through mesenchymal stem cells and various growth factors, but these strategies have been constrained in the aspects of security and economy. Hence, there is an urgent need to find new ways to promote tissue repair and regeneration. There have been a lot of evidences showing that the immune system plays an important role in tissue regeneration and repair. In recent years, more and more studies have been done on adaptive immunity in tissue repair, especially the regulatory T cells. Some evidences indicate that regulatory T cells participate in damage tissue repair and regeneration of multiple organs and tissue. This review briefly introduces the new advances in the repair effects and regulatory mechanism of regulatory T cells in different organ injuries, in order to provide new ideas for designing advanced repair materials with good immunoregulatory functions.


Assuntos
Regeneração , Linfócitos T Reguladores/imunologia , Cicatrização/imunologia , Humanos , Medicina Regenerativa/tendências
3.
Eur J Histochem ; 63(3)2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31696691

RESUMO

Recently, the development and the application of 3D scaffold able to promote stem cell differentiation represented an essential field of interest in regenerative medicine. In particular, functionalized scaffolds improve bone tissue formation and promote bone defects repair. This research aims to evaluate the role of ascorbic acid (AS) supplementation in an in vitro model, in which a novel 3D-scaffold, bovine pericardium collagen membrane called BioRipar (BioR) was functionalized with human Gingival Mesenchymal Stem Cells (hGMSCs). As extensively reported in the literature, AS is an essential antioxidant molecule involved in the extracellular matrix secretion and in the osteogenic induction. Specifically, hGMSCs were seeded on BioR and treated with 60 and 90 µg/mL of AS in order to assess their growth behavior, the expression of bone specific markers involved in osteogenesis (runt-related transcription factor 2, RUNX2; collagen1A1, COL1A1; osteopontin, OPN; bone morphogenetic protein2/4, BMP2/4), and de novo deposition of calcium. The expression of COL1A1, RUNX2, BMP2/4 and OPN was evaluated by RT-PCR, Western blotting and immunocytochemistry, and proved to be upregulated. Our results demonstrate that after three weeks of treatment AS at 60 and 90 µg/mL operates as an osteogenic inductor in hGMSCs. These data indicate that the AS supplementation produces an enhancement of osteogenic phenotype commitment in an in vitro environment. For this reason, AS could represent a valid support for basic and translational research in tissue engineering and regenerative medicine.


Assuntos
Ácido Ascórbico/metabolismo , Colágeno Tipo I/metabolismo , Células-Tronco Mesenquimais/metabolismo , Pericárdio/metabolismo , Tecidos Suporte/química , Animais , Biomarcadores/metabolismo , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 4/metabolismo , Bovinos , Diferenciação Celular/fisiologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Gengiva/metabolismo , Humanos , Osteogênese/fisiologia , Osteopontina/metabolismo , Pericárdio/citologia , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos
4.
Adv Exp Med Biol ; 1174: 371-399, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31713206

RESUMO

Biomaterials play a critical role in regenerative strategies such as stem cell-based therapies and tissue engineering, aiming to replace, remodel, regenerate, or support damaged tissues and organs. The design of appropriate three-dimensional (3D) scaffolds is crucial for generating bio-inspired replacement tissues. These scaffolds are primarily composed of degradable or non-degradable biomaterials and can be employed as cells, growth factors, or drug carriers. Naturally derived and synthetic biomaterials have been widely used for these purposes, but the ideal biomaterial remains to be found. Researchers from diversified fields have attempted to design and fabricate novel biomaterials, aiming to find novel theranostic approaches for tissue engineering and regenerative medicine. Since no single biomaterial has been found to possess all the necessary characteristics for an ideal performance, over the years scientists have tried to develop composite biomaterials that complement and combine the beneficial properties of multiple materials into a superior matrix. Herein, we highlight the structural features and performance of various biomaterials and their application in regenerative medicine and for enhanced tissue engineering approaches.


Assuntos
Biomimética , Matriz Extracelular , Engenharia Tecidual , Materiais Biocompatíveis/química , Matriz Extracelular/química , Medicina Regenerativa , Tecidos Suporte/química , Tecidos Suporte/normas
6.
Adv Dent Res ; 30(2): 50-56, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31633385

RESUMO

Tissue injuries in the oral and maxillofacial structures secondary to trauma, warfare, ablative cancer, and benign tumor surgery result in significant losses of speech, masticatory and swallowing functions, aesthetic deformities, and overall psychological stressors and compromise. Optimal oral rehabilitation remains a formidable challenge and an unmet clinical need due to the influence of multiple factors related to the physiologic limitations of tissue repair, the lack of site and function-specific donor tissues and constructs, and an integrated team of multidisciplinary professionals. The advancements in stem cell biology, biomaterial science, and tissue engineering technologies, particularly the 3-dimensional bioprinting technology, together with digital imaging and computer-aided design and manufacturing technologies, have paved the path for personalized/precision regenerative medicine. At the University of Pennsylvania, we have launched the initiative to integrate multidisciplinary health professionals and translational/clinical scientists in medicine, dentistry, stem cell biology, tissue engineering, and regenerative medicine to develop a comprehensive, patient-centered approach for precision and personalized reconstruction, as well as oral rehabilitation of patients sustaining orofacial tissue injuries and defects, especially oral cancer patients.


Assuntos
Bioimpressão , Boca , Impressão Tridimensional , Engenharia Tecidual , Estética Dentária , Humanos , Boca/lesões , Medicina Regenerativa
7.
Arq. bras. med. vet. zootec. (Online) ; 71(5): 1571-1581, set.-out. 2019. graf, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1038673

RESUMO

There is a growing interest in the study of unspecialized mesenchymal stem cells, for there are still some discussions about their in vitro behavior. Regenerative medicine is a science undergoing improvement which develops treatments as cell therapy using somatic stem cells. In several studies, adipose tissue is presented as a source of multipotent adult cells that has several advantages over other tissue sources. This study aimed to characterize and evaluate the tagging of mesenchymal stem cells from the agoutis adipose tissue (Dasyprocta prymonolopha), with fluorescent intracytoplasmic nanocrystals. Fibroblast cells were observed, plastic adherent, with extended self-renewal, ability to form colonies, multipotency by differentiation into three lineages, population CD90 + and CD45 - expression, which issued high red fluorescence after the tagging with fluorescent nanocrystals by different paths and cryopreserved for future use. It is possible to conclude that mesenchymal stem cells from agouti adipose tissue have biological characteristics and in vitro behavior that demonstrate its potential for use in clinical tests.(AU)


Há um interesse crescente no estudo das células estaminais mesenquimais, não especializadas, pois ainda existem algumas discussões sobre seu comportamento in vitro. A medicina regenerativa é uma ciência em fase de crescimento que desenvolve tratamentos como terapia celular utilizando células estaminais somáticas. Em vários estudos, o tecido adiposo é apresentado como uma fonte de células adultas multipotentes que tem várias vantagens em relação a outras fontes de tecido. Este estudo teve como objetivo caracterizar e avaliar a marcação de células estaminais mesenquimais do tecido adiposo de cutias (Dasyprocta prymnolopha) com nanocristais intracitoplasmáticos fluorescentes. Observaram-se células fibroblásticas, aderentes ao plástico, com autorrenovação prolongada, capacidade de formar colônias, diferenciação em três linhagens, população CD90 + e expressão CD45, que emitiram alta fluorescência vermelha após a marcação com nanocristais fluorescentes por diferentes vias, e criopreservadas para uso futuro. É possível concluir que as células estaminais mesenquimais do tecido adiposo de cutias têm características biológicas e comportamentos in vitro que demonstram seu potencial para uso em testes clínicos.(AU)


Assuntos
Animais , Tecido Adiposo/citologia , Imunofenotipagem/veterinária , Medicina Regenerativa/métodos , Nanopartículas , Células-Tronco Mesenquimais , Dasyproctidae/genética
8.
Invest Ophthalmol Vis Sci ; 60(12): 4008-4020, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31560364

RESUMO

Purpose: The injection of cultured human corneal endothelial cells (cHCECs) into the anterior chamber (AC) is a newly developed modality for the successful treatment of corneal endothelium dysfunction. Here, we investigated whether or not cHCECs could be labeled using quantum dots (QDs) composed of semiconductor nanoparticle octa-arginine (R8) to trace injected cHCECs and examined the utility of in vivo fluorescence imaging to analyze the dynamics and accumulation of QD-labeled injected cHCECs in a corneal endothelial dysfunction mouse model. Methods: The cHCECs, either of high quality or with cell-state transition, were labeled by adding a mixture of QDs655 and R8. The labeling efficiency and the unchanging of the cell phenotypes by the labeling was confirmed by flow cytometry. The labeled cHCECs were injected into the AC of either healthy mice or mice with corneal endothelium damaged by cryogenic treatment. The kinetics of the injected cHCECs was traced quantitatively via multiphoton confocal laser microscopy. Results: QD labeling induced no morphologic change in the cHCECs or in the expression of the functional markers of cHCECs (i.e., Na+/K+-ATPase and zonula occludens-1). The injected cHCECs-QDs were quantitatively detected, and the retention of cHCECs-QDs was evident, from 3 to 48 hours post cell injection on the posterior surface in the cryogenically injured corneal endothelium mouse model eyes, yet not in the noninjured healthy control eyes. Conclusions: The findings of this study show that in the field of regenerative medicine, QD labeling of cells presents a convenient and sensitive method of finely monitoring the fate of injected cells in vivo.


Assuntos
Câmara Anterior/metabolismo , Epitélio Posterior/metabolismo , Pontos Quânticos , Adulto , Animais , Biomarcadores/metabolismo , Contagem de Células , Diferenciação Celular , Células Cultivadas , Citometria de Fluxo , Humanos , Injeções Intraoculares , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Microscopia de Contraste de Fase , Medicina Regenerativa/métodos , ATPase Trocadora de Sódio-Potássio/metabolismo , Doadores de Tecidos , Adulto Jovem , Proteína da Zônula de Oclusão-1/metabolismo
9.
Dent Mater J ; 38(6): 867-883, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31511473

RESUMO

The aim of the systematic review was to analyze the use of mesenchymal stem cells (MSC) and biomaterial for periodontal regeneration from preclinical animal models and human. Electronic databases were searched and additional hand-search in leading journals was performed. The research strategy was achieved according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The including criteria were as follows: MSC, biomaterial, in vivo studies, with histologic and radiologic analysis and written in English. The risk of bias was assessed for individual studies. A total of 50 articles were selected and investigated in the systematic review. These results indicate that MSC and scaffold provide beneficial effects on periodontal regeneration, with no adverse effects of such interventions. Future studies need to identify the suitable association of MSC and biomaterial and to characterize the type of new cementum and the organization of the periodontal ligament fiber regeneration.


Assuntos
Células-Tronco Mesenquimais , Medicina Regenerativa , Animais , Materiais Biocompatíveis , Cemento Dentário , Humanos , Ligamento Periodontal
10.
Life Sci ; 236: 116861, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31513815

RESUMO

Osteoarthritis is a prevalent worldwide joint disease, which demonstrates a remarkable adverse effect on the patients' life modality. Medicinal agents, exclusively nonsteroidal anti-inflammatory drugs (NSAIDs), have been routinely applied in the clinic. But, their effects are restricted to pain control with insignificant effects on cartilage renovation, which would finally lead to cartilage destruction. In the field of regenerative medicine, many researchers have tried to use stem cells to repair tissues and other human organs. However, in recent years, with the discovery of extracellular microvesicles, especially exosomes, researchers have been able to offer more exciting alternatives on the subject. Exosomes and microvesicles are derived from different types of bone cells such as mesenchymal stem cells, osteoblasts, and osteoclasts. They are also recognized to play substantial roles in bone remodeling processes including osteogenesis, osteoclastogenesis, and angiogenesis. Specifically, exosomes derived from a mesenchymal stem cell have shown a great potential for the desired purpose. Exosomal products include miRNA, DNA, proteins, and other factors. At present, if it is possible to extract exosomes from various stem cells effectively and load certain products or drugs into them, they can be used in diseases, such as rheumatoid arthritis, osteoarthritis, bone fractures, and other diseases. Of course, to achieve proper clinical use, advances have to be made to establish a promising regenerative ability for microvesicles for treatment purposes in the orthopedic disorders. In this review, we describe the exosomes biogenesis and bone cell derived exosomes in the regenerate process of bone and cartilage remodeling.


Assuntos
Cartilagem Articular/citologia , Exossomos/transplante , Osteoartrite/terapia , Osteogênese , Células-Tronco/citologia , Humanos , Osteoartrite/complicações , Osteoartrite/patologia , Medicina Regenerativa
11.
EMBO J ; 38(19): e103148, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31475380

RESUMO

It is now recognized that cell identity is more fluid, and tissues more plastic, than previously thought. The plasticity of cells is relevant to diverse fields, most notably developmental and stem cell biology, regenerative medicine, and cancer biology. To date, a comprehensive and uniform nomenclature to define distinct cell states and their injury-induced interconversions has been elusive. The first Keystone Symposium devoted exclusively to cellular plasticity in regeneration and tumorigenesis was held on January 2019 in Keystone, Colorado, and featured a workshop on terminology in the cell plasticity field. Definitions for terms such as plasticity, de- and transdifferentiation, reversion, and paligenosis were discussed. Here, we summarize the content and tenor of the symposium and nomenclature-focused workshop with regard to terms in the field. We outline the challenges with current definitions and recommend best practices and approaches to developing an accurate and acceptable nomenclature in the future.


Assuntos
Plasticidade Celular , Terminologia como Assunto , Animais , Carcinogênese , Congressos como Assunto , Humanos , Plásticos , Medicina Regenerativa
13.
Mater Sci Eng C Mater Biol Appl ; 104: 109942, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499951

RESUMO

Decellularized matrix (dECM) is isolated extracellular matrix of tissues from its original inhabiting cells, which has emerged as a promising natural biomaterial for tissue engineering, aiming at support, replacement or regeneration of damaged tissues. The dECM can be easily obtained from tissues/organs of various species by adequate decellularization methods, and mimics the structure and composition of the native extracellular matrix, providing a favorable cellular environment. In this review, we summarize the recent developments in the preparation of dECM materials, including decellularization, crosslinking and sterilization. Also, we cover the advances in the utilization of dECM biomaterials in regeneration medicine in pre-clinic and clinical trials. Moreover, we highlight those emerging medical benefits of dECM beyond tissue engineering, such as cell transplantation, in vitro/in vivo model and therapeutic cues delivery. With the advances in the preparation and broader application, the dECM biomaterials could become the gold scaffold and pharmaceutical excipients in medical sciences.


Assuntos
Materiais Biocompatíveis/química , Matriz Extracelular/química , Matriz Extracelular/efeitos dos fármacos , Animais , Humanos , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Tecidos Suporte/química
14.
J Biosci ; 44(4)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31502583

RESUMO

It has been proposed that age reprogramming enables old cells to be rejuvenated without passage through an embryonic stage (Singh and Zacouto in J. Biosci. 35 315-319, 2010). As such, age reprogramming stands apart from the induced pluripotent stem (iPS) and nuclear transfer-embryonic stem (NT-ES) cell therapies where histo-compatible cells are produced only after passage through an embryonic stage. It avoids many of the disadvantages associated with iPS and NT-ES cell therapies. Experimental evidence in support of age reprogramming is burgeoning. Here, we discuss possible new approaches to enhance age reprogramming, which will have considerable benefits for regenerative therapies.


Assuntos
Envelhecimento/genética , Reprogramação Celular/genética , Epigênese Genética/genética , Células-Tronco Embrionárias/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Medicina Regenerativa
15.
Life Sci ; 233: 116733, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31394127

RESUMO

Exosomes are extracellular vesicles with the size of 40-100 nm in diameter and a density of 1.13-1.19 g/mL, containing proteins, mRNAs, miRNAs, and DNAs. Exosomes change the recipient cells biochemical features through biomolecules delivery and play a role in cellular communication. These vesicles are produced from body fluids and different cell types like mesenchymal stem cells (MSCs). Evidence suggests that mesenchymal stem cells-derived exosome (MSC-EXO) exhibit functions similar to MSCs with low immunogenicity and no tumorization. MSCs can also be isolated from a variety of sources including human umbilical cord (HUC). Because of the non-invasive collection method, higher proliferation and lower immunogenicity, HUCMSC-EXO has been frequently used in regenerative medicine and various diseases treatment compared to the other MSC-EXO resources. This review aimed to investigate the applications of HUCMSC-EXO in different diseases.


Assuntos
Doença , Exossomos/fisiologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Medicina Regenerativa , Cordão Umbilical/citologia , Animais , Humanos
17.
Int J Mol Sci ; 20(17)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466409

RESUMO

This systematic review is aimed at evaluating the effectiveness of synthetic block materials for bone augmentation in preclinical in vivo studies. An electronic search was performed on Pubmed, Scopus, EMBASE. Articles selected underwent risk-of-bias assessment. The outcomes were: new bone formation and residual graft with histomorphometry, radiographic bone density, soft tissue parameters, complications. Meta-analysis was performed to compare new bone formation in test (synthetic blocks) vs. control group (autogenous blocks or spontaneous healing). The search yielded 214 articles. After screening, 39 studies were included, all performed on animal models: rabbits (n = 18 studies), dogs (n = 4), rats (n = 7), minipigs (n = 4), goats (n = 4), and sheep (n = 2). The meta-analysis on rabbit studies showed significantly higher new bone formation for synthetic blocks with respect to autogenous blocks both at four-week (mean difference (MD): 5.91%, 95% confidence intervals (CI): 1.04, 10.79%, p = 0.02) and at eight-week healing (MD: 4.44%, 95% CI: 0.71, 8.17%, p = 0.02). Other animal models evidenced a trend for better outcomes with synthetic blocks, though only based on qualitative analysis. Synthetic blocks may represent a viable resource in bone regenerative surgery for achieving new bone formation. Differences in the animal models, the design of included studies, and the bone defects treated should be considered when generalizing the results. Clinical studies are needed to confirm the effectiveness of synthetic blocks in bone augmentation procedures.


Assuntos
Regeneração Óssea , Substitutos Ósseos/uso terapêutico , Animais , Substitutos Ósseos/efeitos adversos , Substitutos Ósseos/química , Cães , Cabras , Coelhos , Ratos , Medicina Regenerativa/métodos , Ovinos , Suínos , Porco Miniatura
18.
Int J Mol Sci ; 20(17)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438477

RESUMO

Collagen is the most widespread extracellular matrix (ECM) protein in the body and is important in maintaining the functionality of organs and tissues. Studies have explored interventions using collagen-targeting tissue engineered techniques, using collagen hybridizing or collagen binding peptides, to target or treat dysregulated or injured collagen in developmental defects, injuries, and diseases. Researchers have used collagen-targeting peptides to deliver growth factors, drugs, and genetic materials, to develop bioactive surfaces, and to detect the distribution and status of collagen. All of these approaches have been used for various regenerative medicine applications, including neovascularization, wound healing, and tissue regeneration. In this review, we describe in depth the collagen-targeting approaches for regenerative therapeutics and compare the benefits of using the different molecules for various present and future applications.


Assuntos
Colágeno/metabolismo , Matriz Extracelular/metabolismo , Peptídeos/metabolismo , Medicina Regenerativa/tendências , Animais , Humanos , Engenharia Tecidual
19.
Nat Commun ; 10(1): 3491, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375674

RESUMO

Despite the wide applications, systematic mechanobiological investigation of 3D porous scaffolds has yet to be performed due to the lack of methodologies for decoupling the complex interplay between structural and mechanical properties. Here, we discover the regulatory effect of cryoprotectants on ice crystal growth and use this property to realize separate control of the scaffold pore size and stiffness. Fibroblasts and macrophages are sensitive to both structural and mechanical properties of the gelatin scaffolds, particularly to pore sizes. Interestingly, macrophages within smaller and softer pores exhibit pro-inflammatory phenotype, whereas anti-inflammatory phenotype is induced by larger and stiffer pores. The structure-regulated cellular mechano-responsiveness is attributed to the physical confinement caused by pores or osmotic pressure. Finally, in vivo stimulation of endogenous fibroblasts and macrophages by implanted scaffolds produce mechano-responses similar to the corresponding cells in vitro, indicating that the physical properties of scaffolds can be leveraged to modulate tissue regeneration.


Assuntos
Materiais Biocompatíveis/química , Crioprotetores/farmacologia , Porosidade/efeitos dos fármacos , Tecidos Suporte/química , Cicatrização , Animais , Proliferação de Células , Modelos Animais de Doenças , Fibroblastos , Gelatina/química , Gelatina/efeitos dos fármacos , Humanos , Macrófagos , Masculino , Teste de Materiais/métodos , Camundongos , Cultura Primária de Células , Medicina Regenerativa/métodos , Pele/lesões , Resistência à Tração
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