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1.
Plast Reconstr Surg ; 145(2): 409-418, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31985633

RESUMO

BACKGROUND: Irradiated allogeneic costal cartilage is an alternative option of cartilage graft in patients with insufficient autologous cartilage. However, complications can occur during long-term follow-up. This study investigated whether Tutoplast-processed cartilage, one of the irradiated allogeneic costal cartilages, acts as a scaffold for adipose-derived stem cells and chondrogenesis. METHODS: In vitro setting, human adipose-derived stem cells seeded onto Tutoplast-processed cartilage were cultured in chondrogenic medium and observed using a scanning electron microscope. Next, 3 types of irradiated cartilage-including Tutoplast-processed cartilage, undifferentiated stem cells on Tutoplast-processed cartilage (undifferentiated group), and chondrogenic differentiated stem cells on Tutoplast-processed cartilage (chondrogenic group)-were implanted subcutaneously into nude mice. Gross, histologic, and gene expression analyses of Tutoplast-processed cartilages were performed at postoperative weeks 2 and 4. RESULTS: Human adipose-derived stem cells subjected to in vitro three-dimensional culture differentiated into chondrocytes and expressed cartilage-specificgenes. Adipose-derived stem cells seeded onto Tutoplast-processed cartilage were differentiated into chondrocytes in chondrogenic medium. In the chondrogenic group, the chondrogenic-differentiated cells attached to the surface of the Tutoplast-processed cartilage were maintained during the follow-up and were distinct from the existing Tutoplast-processed cartilage. Moreover, the chondrogenic group had higher expression of cartilage-specific genes compared with the undifferentiated group. CONCLUSIONS: Adipose-derived stem cells seeded onto Tutoplast-processed cartilage underwent chondrogenic differentiation, generating new cartilage, which was maintained after implantation without critical complications. The findings are clinically valuable in terms of overcoming the limitations of irradiated allogeneic costal cartilage, and broaden the surgical options for treatments requiring cartilage.


Assuntos
Cartilagem/fisiologia , Condrogênese/fisiologia , Células-Tronco Mesenquimais/fisiologia , Agrecanas/metabolismo , Animais , Biomarcadores/metabolismo , Cartilagem/efeitos da radiação , Diferenciação Celular/fisiologia , Células Cultivadas , Colágeno Tipo X/metabolismo , Feminino , Humanos , Técnicas In Vitro , Injeções Subcutâneas , Músculos Intercostais , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos Nus , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Modelos Animais , Reação em Cadeia da Polimerase em Tempo Real , Transplante Heterólogo , Transplante Homólogo
2.
Gene ; 732: 144336, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31935514

RESUMO

In the present study, we aimed to evaluate effects of autologous mesenchymal stem cells (MSCs) intravenous administration on the response of B cells, BAFF, APRIL, and their receptors on the surface of B cells at 1, 6, and 12 month follow-up periods in refractory rheumatoid arthritis (RA) patients. Thirteen patients with refractory RA received autologous MSCs. Plasma levels of BAFF and APRIL were measured employing ELISA method, followed by estimating B cell population and BAFFRs evaluation by flow cytometry technique. Gene expression of BAFF, APRIL, and their receptors on B cell surface in PBMCs was evaluated by SYBR Green real-time PCR technique. Plasma concentration of BAFF significantly decreased 1 and 6 months after the MSCT (MSCs Transplantation). Plasma concentration of APRIL significantly decreased 1 month after the MSCT. Percentages of CD19 + B cells in the PBMC population significantly decreased 12 months after the MSCT. Percentages of BR3 + CD19 + B cells and BCMA + CD19 + B cells significantly decreased at the 12th month after the MSCT. The gene expression of BAFF in the PBMC population significantly decreased during 6, and 12 months after the MSCT. The gene expression of APRIL significantly decreased on month 6 after the MSCT. The gene expression of BR3 significantly decreased during 1, 6, and 12 months after the MSCT. The MSCT seems to decrease B cells response because of the reduced production of BAFF and APRIL cytokines and decrease the expression of their receptors on the surface of B cells.


Assuntos
Artrite Reumatoide/terapia , Fator Ativador de Células B/metabolismo , Receptor do Fator Ativador de Células B/metabolismo , Regulação para Baixo , Transplante de Células-Tronco Mesenquimais/métodos , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Administração Intravenosa , Adulto , Antígenos CD19/metabolismo , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Fator Ativador de Células B/genética , Receptor do Fator Ativador de Células B/genética , Linfócitos B/imunologia , Feminino , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética
3.
Medicine (Baltimore) ; 98(49): e18199, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804341

RESUMO

BACKGROUND: Approximately 10% to 30% patients develop delayed encephalopathy after acute CO poisoning (DEACMP). No specific treatment is available and poor prognosis is a characteristic of this disease. We aimed to evaluate the efficacy and safety of all therapies that have been tried in randomized controlled trial (RCT) for DEACMP. METHODS: We conducted a systematic search of the Cochrane, Embase, PubMed, and Web of Science databases. RESULTS: Overall, 4 RCTs were identified in our study. Both hyperbaric oxygen (HBO) and mesenchymal stem cell (MSC) transplantation were effective in DEACMP, and MSC seemed to be superior to HBO. The addition of dexamethasone, N-butylphthalide, or XingZhi-YiNao granules into HBO, or butylphthalide into MSC could achieve better neurological recovery in DEACMP patients but did not significantly increase the incidence of adverse events. CONCLUSION: Several therapies have shown positive results in treating DEACMP and need to be proven by further studies.


Assuntos
Encefalopatias/etiologia , Encefalopatias/terapia , Intoxicação por Monóxido de Carbono/complicações , Benzofuranos/uso terapêutico , Dexametasona/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Oxigenação Hiperbárica/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
5.
Adv Gerontol ; 32(3): 370-374, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31512423

RESUMO

The aim of this research was to study the migration of multipotent mesenchymal stromal cells (MMSC) in old laboratory animals under physiological conditions and after liver resection. Different routes of administration were used: to the caudal vein, intraperitoneal, hepatic artery, portal vein. Studies have shown the ability of the old organism to respond to changes in the directed migration of MMSCs in the tissues that have undergone the greatest damage, which may be due to the production of connective tissue of the damaged organ chemoattractant. In contrast intraperitoneal, other delivery methods MMSC: tail vein, v. portae, a. hepatica, are more effective.


Assuntos
Movimento Celular , Fígado , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Animais de Laboratório , Fígado/cirurgia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia
6.
Life Sci ; 235: 116830, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31487529

RESUMO

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS). In attempt to identify an appropriate treatment for improving the neurological symptoms and remyelination process, autologous and allogenic transplantation of mesenchymal stem cells (MSCs) have been introduced as an effective therapeutic strategy in MS. MSCs are a heterogeneous subset of pluripotent non-hematopoietic stromal cells that are isolated from bone marrow, adipose tissue, placenta and other sources. MSCs have considerable therapeutic effects due to their ability in differentiation, migration, immune-modulation and neuroregeneration. To date, numerous experimental and clinical studies demonstrated that MSCs therapy improves the CNS repair and modulates functional neurological symptoms. Here, we provided an overview of the current knowledge about the clinical applications of MSCs in MS. Furthermore, the major challenges and risks of MSCs therapy in MS patients have been elucidated.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Esclerose Múltipla/terapia , Animais , Humanos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Esclerose Múltipla/patologia
7.
Life Sci ; 233: 116740, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31398416

RESUMO

Although intravenous injection is the most convenient and feasible approach for mesenchymal stem cells (MSCs) delivery, the proportion of donor stem cells in the target myocardium after transplantation is small. It is believed that TCM enhances the effect of stem cell therapy by improving the hostile microenvironment and promoting the migration and survival of stem cells. Guanxin Danshen (GXDS) formulation is one of the main prescriptions for clinical treatment of ischemic heart diseases in China. The purpose of this study was to evaluate the effects of GXDS formulation administration combined with MSCs transplantation on cardiac function improvement, apoptosis, angiogenesis and survival of transplanted cells in an acute model of acute myocardial infarction (MI). After being labeled with GFP, MSCs were transplanted via intravenous injection. Meanwhile, GXDS dripping pills were given by intragastric administration for 4 weeks from 2 days before MI. Echocardiography showed moderate improvement in cardiac function after administration of GXDS formulation or intravenous transplantation of MSCs. However, GXDS formulation combined with MSCs transplantation significantly improved cardiac function after MI. The myocardial infarct size in rats treated with MSCs was similar to that in rats treated with GXDS formulation. However, GXDS formulation combined with MSCs transplantation significantly reduced infarction area. In addition, GXDS formulation combined with MSCs transplantation not only decreased cell apoptosis according to the TUNEL staining, but also enhanced angiogenesis in the peri-infarction and infarction area. Interestingly, the use of GXDS formulation increased the number of injected MSCs in the infarct area. Furthermore, GXDS formulation combined with MSCs transplantation increased SDF-1 levels in the infarcted area, but did not affect the expression of YAP. Our study provided a more feasible and accessible strategy to enhance the migration of stem cells after intravenous injection by oral administration of GXDS formulation. The combination of GXDS formulation and stem cell therapy has practical significance and application prospects in the treatment of ischemic cardiomyopathy such as MI.


Assuntos
Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Infarto do Miocárdio/terapia , Neovascularização Patológica/prevenção & controle , Animais , Células Cultivadas , Terapia Combinada , Sobrevivência de Enxerto , Masculino , Infarto do Miocárdio/patologia , Ratos
8.
Int J Mol Sci ; 20(15)2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31366040

RESUMO

Wound healing is a complex process with a linear development that involves many actors in a multistep timeline commonly divided into four stages: Hemostasis, inflammation, proliferation, and remodeling. Chronic non-healing wounds fail to progress beyond the inflammatory phase, thus precluding the next steps and, ultimately, wound repair. Many intrinsic or extrinsic factors may contribute to such an occurrence, including patient health conditions, age-related diseases, metabolic deficiencies, advanced age, mechanical pressure, and infections. Great interest is being focused on the adipose tissue-derived stem cell's (ASC) paracrine activity for its potential therapeutic impact on chronic non-healing wounds. In this review, we summarize the results of in vitro and in vivo experimental studies on the pro-wound healing effects of ASC-secretome and/or extracellular vesicles (EVs). To define an overall picture of the available literature data, experimental conditions and applied methodologies are described as well as the in vitro and in vivo models chosen in the reported studies. Even if a comparative analysis of the results obtained by the different groups is challenging due to the large variability of experimental conditions, the available findings are undoubtedly encouraging and fully support the use of cell-free therapies for the treatment of chronic non-healing wounds.


Assuntos
Tecido Adiposo/citologia , Vesículas Extracelulares/transplante , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Cicatrização , Tecido Adiposo/metabolismo , Animais , Vesículas Extracelulares/metabolismo , Humanos
9.
BMC Musculoskelet Disord ; 20(1): 335, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324245

RESUMO

BACKGROUND: Previous basic research and clinical studies examined the effects of mesenchymal stem cells (MSCs) on regeneration and maintenance of articular cartilage. However, our pilot study suggested that MSCs are more effective at suppressing inflammation and pain rather than promoting cartilage regeneration in osteoarthritis. Adipose tissue is considered a useful source of MSCs; it can be harvested easily in larger quantities compared with the bone marrow. The present study was designed to evaluate the anti-inflammatory, analgesic, and regenerative effects of intra-articularly injected processed lipoaspirate (PLA) cells (containing adipose-derived MSCs) on degenerative cartilage in a rat osteoarthritis model. METHODS: PLA cells were isolated from subcutaneous adipose tissue of 12-week-old female Sprague-Dawley rats. Osteoarthritis was induced by injection of monoiodoacetate (MIA). Each rat received 1 × 106 MSCs into the joint at day 7 (early injection group) and day 14 (late injection group) post-MIA injection. At 7, 14, 21 days after MIA administration, pain was assessed by immunostaining and western blotting of dorsal root ganglion (DRG). Cartilage quality was assessed macroscopically and by safranin-O and H&E staining, and joint inflammation was assessed by western blotting of the synovium. RESULTS: The early injection group showed less cartilage degradation, whereas the late injection group showed cartilage damage similar to untreated OA group. The relative expression level of CGRP protein in DRG neurons was significantly lower in the two treatment groups, compared with the untreated group. CONCLUSIONS: Intra-articular injection of PLA cells prevented degenerative changes in the early injection group, but had little effect in promoting cartilage repair in the late injection group. Interestingly, intra-articular injection of PLA cells resulted in suppression of inflammation and pain in both OA groups. Further studies are needed to determine the long-term effects of intra-articular injection of PLA cells in osteoarthritis.


Assuntos
Artralgia/terapia , Artrite Experimental/terapia , Cartilagem Articular/patologia , Transplante de Células-Tronco Mesenquimais/métodos , Osteoartrite/terapia , Tecido Adiposo/citologia , Animais , Artralgia/diagnóstico , Artralgia/etiologia , Artrite Experimental/induzido quimicamente , Biomarcadores/análise , Feminino , Gânglios Espinais/patologia , Humanos , Injeções Intra-Articulares , Ácido Iodoacético/toxicidade , Articulação do Joelho/inervação , Articulação do Joelho/patologia , Osteoartrite/induzido quimicamente , Osteoartrite/patologia , Medição da Dor/métodos , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento
10.
BMC Gastroenterol ; 19(1): 124, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299915

RESUMO

BACKGROUND: Bone mesenchymal stromal cells (BMSC) showed protective potential against intestinal ischemia. Oxygenase-1(HO-1) could alleviate oxidative stress. In the present study, we constructed HO-1-expressing BMSC and detected the effects of it on survival, intestinal injury and inflammation following intestinal ischemia and reperfusion injury (I/R). METHODS: In this experiment, eighty adult male mice were divided into Sham, I/R, I/R + BMSC, I/R + BMSC/HO-1 groups. Mice were anesthetized and intestinal I/R model were established by temporarily occluding the superior mesenteric artery for 60 min with a non-crushing clamp. Following ischemia, the clamp was removed and the intestines were allowed for reperfusion. Prior to abdominal closure, BMSC/ HO-1 (2 × 106 cells) or BMSC (2 × 106 cells) were injected into the peritoneum of I/R mice respectively. Mice were allowed to recover for 24 h and then survival rate, intestinal injury and inflammation were determined. Reactive oxygen species (ROS) was assayed by fluorescent probe. TNFα and IL-6 were assayed by ELISA. RESULTS: BMSC/HO-1 increased seven day survival rate, improved intestinal injury and down-regulated inflammation after intestinal I/R when compared with sole BMSC (p < 0.05 respectively). Multiple pro-inflammatory media were also decreased following application of BMSC/HO-1, when compared with sole BMSC (p < 0.05) respectively, suggesting that BMSC /HO-1 had a better protection to intestinal I/R than BMSC therapy. CONCLUSION: Administration of BMSC/HO-1 following intestinal I/R, significantly improved intestinal I/R by limiting intestinal damage and inflammation.


Assuntos
Heme Oxigenase-1/metabolismo , Enteropatias , Intestinos , Proteínas de Membrana/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Traumatismo por Reperfusão , Animais , Modelos Animais de Doenças , Regulação para Baixo , Proteínas de Choque Térmico/metabolismo , Inflamação/metabolismo , Inflamação/terapia , Enteropatias/metabolismo , Enteropatias/terapia , Intestinos/irrigação sanguínea , Intestinos/patologia , Masculino , Camundongos , Estresse Oxidativo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/terapia , Resultado do Tratamento
11.
Life Sci ; 232: 116632, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31278944

RESUMO

AIMS: The inflammation modulation effects of mesenchymal stromal cell-derived exosomes (MSC-EXO) are well established. We aimed to explore the mechanism behind the inflammatory responses of numerous exosomal cargo molecules that have been neglected in molecular biology research, and to develop an exosomal cargo delivery system that can exert a stronger therapeutic effect on myocardial ischemia-reperfusion (I/R) injury. MAIN METHODS: Computational approaches were used to identify key exosomal miRNAs and their downstream mRNAs that are expressed in the inflammatory response. Direct interactions between miRNA-181a and the c-Fos mRNA complex were confirmed by luciferase reporter assay. MSC-EXO carrying miRNA-181a-overexpressing lentiviruses were intramyocardially injected into a mouse model of myocardial I/R injury. I/R progression was evaluated through echocardiography and immunofluorescence microscopy. KEY FINDINGS: miRNA-181a provided substantial coverage against a host of immune-related genes through the miRNA-mRNA network. miRNA-181a delivery by MSC-EXO combined the immune-suppressing effect of miRNA-181a and the cell targeting capability of MSC-EXO to exert a stronger therapeutic effect on myocardium I/R injury. SIGNIFICANCE: We showed the potential of MSC-EXO as a tool for the specific delivery of small RNAs in vivo. This study shed new light on the potential application of miRNA-181a-overexpressing MSC-EXO as a therapeutic strategy for myocardial I/R injury.


Assuntos
Células-Tronco Mesenquimais/metabolismo , MicroRNAs/sangue , Traumatismo por Reperfusão Miocárdica/metabolismo , Animais , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Exossomos , Humanos , Inflamação/terapia , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo
12.
J Orthop Surg Res ; 14(1): 204, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272458

RESUMO

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a disabling disease. Early treatment is crucial to the prognosis of the disease. Core decompression (CD) is one of the most commonly used methods for the treatment of early ONFH. But it could not prevent the collapse of the necrotic femoral head. How to improve the therapeutic effect of early ONFH on the basis of CD has become an area of focused research. METHODS: Functional ß-tricalcium phosphate (ß-TCP) scaffolds modified by DPIYALSWSGMA (DPI) peptide, a bone marrow-derived mesenchymal stem cell (BMSC) affinity peptide, were constructed using an adsorption/freeze-drying strategy. The affinity of DPI peptide towards rabbit BMSCs was investigated using flow cytometry and fluorescence cytochemistry. In vitro cell adhesion assay was performed to study the adherent ability of rabbit BMSCs on functional ß-TCP scaffolds. After the rabbit model of early ONFH was established, DPI peptide-modified and pure ß-TCP scaffolds were transplanted into the remaining cavity after CD. Meanwhile, rabbits treated with pure CD were used as blank control. Twelve weeks after surgery, histological analysis was performed to show the therapeutic effect of three methods on early ONFH. RESULTS: The result of ImageXpress Micro Confocal indicated that fabricated DPI peptide-modified functional ß-TCP scaffolds exhibited green fluorescence. In flow cytometry, the average fluorescence intensity for rabbit BMSCs incubated with FITC-DPI was significantly higher than that of FITC-LSP (P = 2.733 × 10-8). In fluorescence cytochemistry, strong fluorescent signals were observed in rabbit BMSCs incubated with FITC-DPI and FITC-RGD, whereas no fluorescent signals in cells incubated with FITC-LSP. In cell adhesion assay, the number of adherent cells to ß-TCP-DPI scaffolds was more than that of pure ß-TCP scaffolds (P = 0.033). The CD + ß-TCP-DPI group expressed the lowest vacant bone lacunae percentage compared to CD group (P = 2.350 × 10-4) and CD + ß-TCP group (P = 0.020). The expression content of COL1 in CD + ß-TCP-DPI group was much higher than CD group (P = 1.262 × 10-7) and CD + ß-TCP group (P = 1.666 × 10-7) according to the integrated optical density (IOD) analyses. CONCLUSION: Functional ß-TCP scaffolds modified by DPI peptide were successfully synthesized using an adsorption/freeze-drying strategy. DPI peptide has good affinity towards rabbit BMSCs. The adhesion of rabbit BMSCs on DPI peptide-modified ß-TCP scaffolds was apparently enhanced. CD followed by implantation of DPI peptide-modified ß-TCP scaffolds can apparently improve the treatment of early ONFH compared with pure CD and CD followed by implantation of unmodified ß-TCP scaffolds. Our current study provides an improved method for the treatment of early ONFH.


Assuntos
Materiais Biocompatíveis/administração & dosagem , Fosfatos de Cálcio/administração & dosagem , Necrose da Cabeça do Fêmur/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Tecidos Suporte , Animais , Células Cultivadas , Necrose da Cabeça do Fêmur/patologia , Masculino , Coelhos
13.
Int J Mol Sci ; 20(14)2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31336890

RESUMO

The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem/stromal cells (MSCs) are able to promote bone regeneration. Their beneficial effects can be improved by modulating the expression levels of specific genes with the purpose of stimulating MSC proliferation, osteogenic differentiation or their immunomodulatory capacity. In this context, the genetic engineering of MSCs is expected to further enhance their pro-regenerative properties and accelerate bone healing. Herein, we review the most promising molecular candidates (protein-coding and non-coding transcripts) and discuss the different methodologies to engineer and deliver MSCs, mainly focusing on in vivo animal studies. Considering the potential of the MSC secretome for bone repair, this topic has also been addressed. Furthermore, the promising results of clinical studies using MSC for bone regeneration are discussed. Finally, we debate the advantages and limitations of using MSCs, or genetically-engineered MSCs, and their potential as promoters of bone fracture regeneration/repair.


Assuntos
Regeneração Óssea , Consolidação da Fratura , Fraturas Ósseas/terapia , Engenharia Genética , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Animais , Biomarcadores , Diferenciação Celular , Estudos Clínicos como Assunto , Modelos Animais de Doenças , Fraturas Ósseas/etiologia , Fraturas Ósseas/patologia , Engenharia Genética/métodos , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Osteogênese , Resultado do Tratamento
14.
Nat Commun ; 10(1): 3123, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311935

RESUMO

Since both myocardium and vasculature in the heart are excessively damaged following myocardial infarction (MI), therapeutic strategies for treating MI hearts should concurrently target both so as to achieve true cardiac repair. Here we demonstrate a concomitant method that exploits the advantages of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) and human mesenchymal stem cell-loaded patch (hMSC-PA) to amplify cardiac repair in a rat MI model. Epicardially implanted hMSC-PA provide a complimentary microenvironment which enhances vascular regeneration through prolonged secretion of paracrine factors, but more importantly it significantly improves the retention and engraftment of intramyocardially injected hiPSC-CMs which ultimately restore the cardiac function. Notably, the majority of injected hiPSC-CMs display adult CMs like morphology suggesting that the secretomic milieu of hMSC-PA constitutes pleiotropic effects in vivo. We provide compelling evidence that this dual approach can be a promising means to enhance cardiac repair on MI hearts.


Assuntos
Coração/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Infarto do Miocárdio/terapia , Miócitos Cardíacos/transplante , Regeneração , Animais , Diferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia , Injeções Intralesionais , Masculino , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/patologia , Miocárdio/citologia , Miocárdio/patologia , Miócitos Cardíacos/fisiologia , Ratos , Ratos Endogâmicos F344 , Resultado do Tratamento
15.
Georgian Med News ; (290): 131-135, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31322530

RESUMO

Reconstruction of mandibular defects is a challenging issue in maxillofacial surgery. Success of the treatment is defined by the process of reparative regeneration of bone tissue, which is often accompanied with wound infection, failure of microcirculation and tissue hypoxia. Aim of our project was to demonstrate the advantage of osteoplastic material and bone marrow derived mesenchymal stem cells combination in regeneration of lower jaw bone defect. For this reason, mandibular bone defect was created in laboratory rats. Experimental treatment of animals was performed in three different ways: group 1. - Bone defect was regenerated without any treatment, group 2. - Bone defect was filled with osteoplastic material (BIO-OSS), group 3. - Bone defect was filled with BIO-OSS, which was previously infiltrated by bone marrow mesenchymal stem cells. Animals were under observation for 6 months. During this period bone regeneration was comparatively analyzed in these tree experimental groups. Observational, histochemical and x-ray research methods were used in this study. Our results suggest that use of osteoplastic material and mesenchymal stem cells combination can increase formation of red bone marrow, which is normally slow under natural condition. Therefore, we can conclude that application of osteoplastic material with bone marrow derived mesenchymal stem cells can decrease time of bone defect osteointegration and define the quality of regenerated bone tissue.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Regeneração Óssea , Substitutos Ósseos , Mandíbula/cirurgia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais , Animais , Osso e Ossos/patologia , Osso e Ossos/cirurgia , Mandíbula/patologia , Ratos , Engenharia Tecidual
16.
J Orthop Surg Res ; 14(1): 198, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262323

RESUMO

BACKGROUND: Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are one of the most potent adult stem cells, capable of differentiating into bone, cartilage, adipose, muscle, and others. An innovative autologous AT-MSC-derived cell-based product (BonoFill-II) for bone tissue regeneration was developed to be suited as a bone graft for segmental bone defects. METHODS: BonoFill-II was transplanted into 8 sheep with 3.2-cm full cortex segmental defect formed in the tibia. Bone regeneration was followed by X-ray radiographs for 12 weeks. At experiment termination, the healed tibia bones were analyzed by computed tomography, histology, and mechanical tests. RESULTS: Our results indicate that one dose of BonoFill-II injectable formula led to an extensive bone growth within the transplantation site and to a complete closure of the critical gap in the sheep's tibia in a relatively short time (8-12 weeks), with no inflammation and no other signs of graft rejection. This new and innovative product opens new prospects for the treatment of long bone defects. CONCLUSIONS: Injection of BonoFill-II (an innovative autologous cell therapy product for bone tissue regeneration) into a critical size segmental defect model (3.2 cm), generated in the sheep tibia, achieved full bridging of the gap in an extremely short period (8-12 weeks).


Assuntos
Regeneração Óssea/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Tíbia/diagnóstico por imagem , Tíbia/fisiologia , Transplante Autólogo/métodos , Animais , Terapia Baseada em Transplante de Células e Tecidos/métodos , Feminino , Humanos , Distribuição Aleatória , Ovinos , Tíbia/lesões
17.
Bone Joint J ; 101-B(7): 824-831, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31256666

RESUMO

AIM: Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model. MATERIALS AND METHODS: Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 106 MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II. RESULTS: Within the PBS injection (control group), typical progressive degenerative changes were revealed in the various knee structures. In the single MSC injection (single group), osteoarthritic changes were attenuated, but still appeared, especially in the medial compartments involving fibrillation of the articular cartilage, osteophyte formation in the medial plateau, and longitudinal tear of the meniscus. In the multiple-injections group, the smoothness and texture of the articular cartilage and meniscus were improved. Histologically, absence or reduction in matrix staining and cellularity were noticeable in the control and single-injection groups, respectively, in contrast to the multiple-injections group, which showed good intensity of matrix staining and chondrocyte distribution in the various cartilage zones. Osteoarthritis Research Society International (OARSI) scoring showed significantly better results in the multiple-injections group than in the other groups. Immunohistochemically, collagen I existed superficially in the medial femoral condyle in the single group, while collagen II was more evident in the multiple-injections group than the single-injection group. CONCLUSION: A single injection of MSCs was not enough to restore the condition of osteoarthritic joints. This is in contrast to multiple injections of MSCs, which had the ability to replace lost cells, as well as reducing inflammation. Cite this article: Bone Joint J 2019;101-B:824-831.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Osteoartrite do Joelho/terapia , Animais , Ligamento Cruzado Anterior/cirurgia , Injeções Intra-Articulares , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/patologia , Coelhos , Transplante Homólogo , Resultado do Tratamento
18.
Int J Mol Sci ; 20(14)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340593

RESUMO

Normothermic machine perfusion (NMP) of kidneys offers the opportunity to perform active interventions, such as the addition of mesenchymal stromal cells (MSCs), to an isolated organ prior to transplantation. The purpose of this study was to determine whether administering MSCs to kidneys during NMP is feasible, what the effect of NMP is on MSCs and whether intact MSCs are retained in the kidney and to which structures they home. Viable porcine kidneys were obtained from a slaughterhouse. Kidneys were machine perfused during 7 h at 37 °C. After 1 h of perfusion either 0, 105, 106 or 107 human adipose tissue derived MSCs were added. Additional ex vivo perfusions were conducted with fluorescent pre-labelled bone-marrow derived MSCs to assess localisation and survival of MSCs during NMP. After NMP, intact MSCs were detected by immunohistochemistry in the lumen of glomerular capillaries, but only in the 107 MSC group. The experiments with fluorescent pre-labelled MSCs showed that only a minority of glomeruli were positive for infused MSCs and most of these glomeruli contained multiple MSCs. Flow cytometry showed that the number of infused MSCs in the perfusion circuit steeply declined during NMP to approximately 10%. In conclusion, the number of circulating MSCs in the perfusate decreases rapidly in time and after NMP only a small portion of the MSCs are intact and these appear to be clustered in a minority of glomeruli.


Assuntos
Rastreamento de Células/métodos , Glomérulos Renais/ultraestrutura , Transplante de Rim , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Perfusão/métodos , Adipócitos/citologia , Adipócitos/fisiologia , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/fisiologia , Diferenciação Celular , Corantes Fluorescentes/metabolismo , Humanos , Glomérulos Renais/cirurgia , Transplante de Células-Tronco Mesenquimais/instrumentação , Células-Tronco Mesenquimais/fisiologia , Microscopia de Fluorescência , Preservação de Órgãos/métodos , Compostos Orgânicos/metabolismo , Perfusão/instrumentação , Suínos , Temperatura Ambiente , Transplante Heterólogo
19.
Curr Pain Headache Rep ; 23(9): 65, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31359164

RESUMO

PURPOSE OF REVIEW: Discogenic low back pain (DLBP) stems from pathology in one or more intervertebral discs identified as the root cause of the pain. It is the most common type of chronic low back pain (LBP), representing 26-42% of attributable cases. RECENT FINDINGS: The clinical presentation of DLBP includes increased pain when sitting, coughing, or sneezing, and experiencing relief when standing or ambulating. Dermatomal radiation of pain to the lower extremity and neurological symptoms including numbness, motor weakness, and urinary or fecal incontinence are signs of advanced disease with disc prolapse, nerve root compression, or spinal stenosis. Degenerative disc disease is caused by both a decrease in disc nutrient supply causing decreased oxygen, lowered pH, and lessened ability of the intervertebral disc (IVD) to respond to increased load or injury; moreover, changes in the extracellular matrix composition cause weakening of the tissue and skewing the extracellular matrix's (ECM) harmonious balance between catabolic and anabolic factors for cell turnover in favor of catabolism. Thus, the degeneration of the disc causes a shift from type II to type I collagen expression by NP cells and a decrease in aggrecan synthesis leads to dehydrated matrix cells ultimately with loss of swelling pressure needed for mechanical support. Cell-based therapies such as autologous nucleus pulposus cell re-implantation have in animal models and human trials shown improvements in LBP score, retention of hydration in IVD, and increased disc height. Percutaneously delivered multipotent mesenchymal stem cell (MSC) therapy has been proposed as a potential means to uniquely ameliorate discogenic LBP holistically through three mechanisms: mitigation of primary nociceptive disc pain, slow or reversal of the catabolic metabolism, and restoration of disc tissue. Embryonic stem cells (ESCs) can differentiate into cells of all three germ layers in vitro, but their use is hindered related to ethical concerns, potential for immune rejection after transplantation, disease, and teratoma formation. Another similar approach to treating back pain is transplantation of the nucleus pulposus, which, like stem cell therapy, seeks to address the underlying cause of intervertebral disc degeneration by aiming to reverse the destructive inflammatory process and regenerate the proteoglycans and collagen found in healthy disc tissue. Preliminary animal models and clinical studies have shown mesenchymal stem cell implantation as a potential therapy for IVD regeneration and ECM restoration via a shift towards favorable anabolic balance and reduction of pain.


Assuntos
Degeneração do Disco Intervertebral/terapia , Dor Lombar/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Células-Tronco Embrionárias/transplante , Humanos , Degeneração do Disco Intervertebral/complicações , Degeneração do Disco Intervertebral/diagnóstico , Dor Lombar/diagnóstico , Dor Lombar/etiologia , Transplante de Células-Tronco Mesenquimais/tendências , Resultado do Tratamento
20.
Int J Mol Sci ; 20(11)2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31181666

RESUMO

Periodontitis is a chronic inflammatory disorder that causes destruction of the periodontal attachment apparatus including alveolar bone, the periodontal ligament, and cementum. Dental implants have been routinely installed after extraction of periodontitis-affected teeth; however, recent studies have indicated that many dental implants are affected by peri-implantitis, which progresses rapidly because of the failure of the immune system. Therefore, there is a renewed focus on periodontal regeneration aroundnatural teeth. To regenerate periodontal tissue, many researchers and clinicians have attempted to perform periodontal regenerative therapy using materials such as bioresorbable scaffolds, growth factors, and cells. The concept of guided tissue regeneration, by which endogenous periodontal ligament- and alveolar bone-derived cells are preferentially proliferated by barrier membranes, has proved effective, and various kinds of membranes are now commercially available. Clinical studies have shown the significance of barrier membranes for periodontal regeneration; however, the technique is indicated only for relatively small infrabony defects. Cytokine therapies have also been introduced to promote periodontal regeneration, but the indications are also for small size defects. To overcome this limitation, ex vivo expanded multipotent mesenchymal stromal cells (MSCs) have been studied. In particular, periodontal ligament-derived multipotent mesenchymal stromal cells are thought to be a responsible cell source, based on both translational and clinical studies. In this review, responsible cell sources for periodontal regeneration and their clinical applications are summarized. In addition, recent transplantation strategies and perspectives about the cytotherapeutic use of stem cells for periodontal regeneration are discussed.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Periodontite/terapia , Engenharia Tecidual/métodos , Animais , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Ligamento Periodontal/citologia , Ligamento Periodontal/fisiologia , Regeneração
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