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1.
Rozhl Chir ; 98(9): 350-355, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31698910

RESUMO

INTRODUCTION: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. METHODS: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. RESULTS: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. CONCLUSION: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Veia Porta , Animais , Cirurgia Endoscópica por Orifício Natural , Suínos , Porco Miniatura , Transplante Autólogo
2.
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
3.
Int J Nanomedicine ; 14: 5925-5942, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534331

RESUMO

Mesenchymal stem cells (MSCs) intrinsically possess unique features that not only help in their migration towards the tumor-rich environment but they also secrete versatile types of secretomes to induce nerve regeneration and analgesic effects at inflammatory sites. As a matter of course, engineering MSCs to enhance their intrinsic abilities is growing in interest in the oncology and regenerative field. However, the concern of possible tumorigenesis of genetically modified MSCs prompted the development of non-viral transfected MSCs armed with nanotechnology for more effective cancer and regenerative treatment. Despite the fact that a large number of successful studies have expanded our current knowledge in tumor-specific targeting, targeting damaged brain site remains enigmatic due to the presence of a blood-brain barrier (BBB). A BBB is a barrier that separates blood from brain, but MSCs with intrinsic features of transmigration across the BBB can efficiently deliver desired drugs to target sites. Importantly, MSCs, when mediated by nanoparticles, can further enhance tumor tropism and can regenerate the damaged neurons in the central nervous system through the promotion of axon growth. This review highlights the homing and nerve regenerative abilities of MSCs in order to provide a better understanding of potential cell therapeutic applications of non-genetically engineered MSCs with the aid of nanotechnology.


Assuntos
Neoplasias Encefálicas/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Nanotecnologia/métodos , Regeneração Nervosa , Animais , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/patologia , Humanos , Tropismo
4.
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
5.
Orthop Clin North Am ; 50(4): 433-443, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31466660

RESUMO

This article serves to provide an overview of molecular and surgical interventions to minimize the progression of posttraumatic arthritis following high-energy intra-articular fractures. The roles of cartilage and the microcellular environment are discussed, as well as the response of the joint and cartilage to injury. Molecular therapies, such as glucocorticoids, mesenchymal stem cells, and bisphosphonates, are presented as potential treatments to prevent progression to posttraumatic arthritis. High-energy intra-articular fractures of the elbow, hip, knee, and ankle are discussed, with emphasis on restoring anatomic alignment, articular reduction, and stability of the joint.


Assuntos
Cartilagem Articular/lesões , Fraturas Intra-Articulares/complicações , Osteoartrite/terapia , Artroplastia , Difosfonatos/uso terapêutico , Progressão da Doença , Glucocorticoides/uso terapêutico , Humanos , Ácido Hialurônico/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Osteoartrite/etiologia
6.
Cancer Radiother ; 23(5): 449-465, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400956

RESUMO

Nowadays, ionizing radiations have numerous applications, especially in medicine for diagnosis and therapy. Pharmacological radioprotection aims at increasing detoxification of free radicals. Radiomitigation aims at improving survival and proliferation of damaged cells. Both strategies are essential research area, as non-contained radiation can lead to harmful effects. Some advances allowing the comprehension of normal tissue injury mechanisms, and the discovery of related predictive biomarkers, have led to developing several highly promising radioprotector or radiomitigator drugs. Next to these drugs, a growing interest does exist for biotherapy in this field, including gene therapy and cell therapy through mesenchymal stem cells. In this review article, we provide an overview of the management of radiation damages to healthy tissues via gene or cell therapy in the context of radiotherapy. The early management aims at preventing the occurrence of these damages before exposure or just after exposure. The late management offers promises in the reversion of constituted late damages following irradiation.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Terapia Genética/métodos , Lesões por Radiação/prevenção & controle , Proteção Radiológica/métodos , Amifostina/uso terapêutico , Animais , Antioxidantes/uso terapêutico , Ensaios Clínicos como Assunto , Fracionamento da Dose de Radiação , Edição de Genes , Vetores Genéticos/uso terapêutico , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Camundongos , Oxirredutases/genética , Oxirredutases/uso terapêutico , Lesões por Radiação/etiologia , Lesões por Radiação/terapia , Lesões Experimentais por Radiação/prevenção & controle , Lesões Experimentais por Radiação/terapia , Protetores contra Radiação/farmacologia , Protetores contra Radiação/uso terapêutico , Proteínas Recombinantes/genética , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo
7.
Zhongguo Gu Shang ; 32(7): 653-657, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31382725

RESUMO

OBJECTIVE: To observe the repair effect of bone marrow mesenchymal stem cells (BMSCs) combined with basic fibroblast growth factor (bFGF) on spinal cord injury in rats and explore its mechanism. METHODS: SD rat BMSCs were obtained by serum culture technique. Eighty healthy 6-week-old male SD rats(weight about 240 g) were randomly divided into 4 groups with 20 each. The sham operation group underwent simple laminectomy without damaging spinal cord and was kept in the same condition as the other 3 groups. The other 3 groups underwent left T9 spinal cord hemisection to establish spinal cord injury model. After 9 days of modeling the local transplantation was performed. The Control group was implanted with gelatin sponge containing normal saline. The BMSCs transplantation group was implanted with gelatin sponge containing BMSCs. The bFGF+BMSCs transplantation group was implanted with gelatin sponge containing bFGF+BMSCs. After 4 and 8 weeks, the expression of NF-200 and GFAP in injured spinal cord tissue was analyzed by Western blotting and the recovery of hind limb function was evaluated by Basso Beattie Bresnahan(BBB) motor function score scale. RESULTS: The BBB scores of BMSCs transplantation group and bFGF+BMSCs transplantation group were better than control group at 4 and 8 weeks after operation (P<0.05) and there was significant difference between bFGF+BMSCs transplantation group and BMSCs transplantation group (P<0.05). After 4 and 8 weeks postoperatively, NF-200 expression was minimal in control group and only a small amount was expressed in BMSCs transplantation group while in bFGF+BMSCs transplantation group NF-200 was highly expressed(P<0.05). GFAP expression was high in control group, middle in BMSCs transplantation group and low in bFGF BMSCs transplantation group(P<0.05). There was significant difference between bFGF+BMSCs transplantation group, BMSCs transplantation group and control group(P<0.05). CONCLUSIONS: The combined transplantation of BMSCs and bFGF can repair the spinal cord injury in rats. The mechanism may be related to the decrease of GFAP expression and the increase of NF-200 expression.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Animais , Células da Medula Óssea , Fator 2 de Crescimento de Fibroblastos , Masculino , Ratos , Ratos Sprague-Dawley , Medula Espinal
8.
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
9.
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
10.
Cell Biochem Funct ; 37(7): 504-515, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31368195

RESUMO

The treatment of neural deficiency after cerebral infarction is challenging, with limited therapeutic options. The transplantation of mesenchymal stem cells (MSCs) to the ischemic penumbra is a potential therapeutic approach. In the present study, a cerebral infarction model was generated by performing middle cerebral artery occlusion (MCAO) in SD rats. The expression of CXCR4 increased, and the number of MSCs migrating to the peri-infarct area was higher in rats transplanted with preconditioned MSCs than in rats transplanted with untreated MSCs. The rate of apoptosis, as evaluated by TUNEL staining and immunoblotting assays, was reduced in rats receiving preconditioned MSCs. A significant amelioration of neural regeneration and improved neurological function were observed in rats injected with preconditioned MSCs compared with those injected with untreated MSCs. However, the application of an siRNA targeting CXCL12 significantly inhibited the protective role of preconditioned MSCs against apoptosis and promoted the migration of MSCs to the ischemic area, leading to impaired neuronal regeneration and limited recovery of neuronal function. Hypoxic preconditioning of MSCs prior to transplantation suppressed apoptosis and increased their migration abilities, leading to the promotion of neuronal regeneration and improvement in neural function after transplantation. This preconditioning strategy may be considered as a potential approach for the modification of MSCs prior to cell transplantation therapy in patients with cerebral infarction. SIGNIFICANCE OF THE STUDY: We found that hypoxic preconditioning of MSCs improved their ability to promote neuronal regeneration and the recovery of neuronal function. Moreover, we showed that CXCR4 inhibited apoptosis, improved cell homing, and promoted neuronal differentiation, without influencing angiogenesis. Our study provides a relatively safe preconditioning method for potential use for cell transplantation therapy in ischemic cerebral infarction. The results presented here will facilitate the development of novel strategies and techniques to improve the tolerance and migration ability of transplanted cells for the treatment of cerebral infarction sequelae.


Assuntos
Infarto Cerebral/metabolismo , Quimiocina CXCL12/metabolismo , Modelos Animais de Doenças , Hipóxia , Células-Tronco Mesenquimais/metabolismo , Receptores CXCR4/metabolismo , Animais , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular , Infarto Cerebral/terapia , Quimiocina CXCL12/antagonistas & inibidores , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos dos fármacos , Neurônios , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores CXCR4/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos
11.
Vet Clin North Am Exot Anim Pract ; 22(3): 441-450, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31395324

RESUMO

Exotic animal orthopedics has not incorporated the most recent progress made in small animal surgery or human medicine. Although minimally invasive osteosynthesis has been incorporated as a routinely used alternative in small animals, its use in exotic animals is still in its infancy. This article compliments the reviews of orthopedics in small mammals, birds, and reptiles in the previous issue. It reviews relevant recent studies performed in laboratory animals about new orthopedic materials and techniques showing potential to become incorporated into the routine orthopedic treatment of exotic animals in the coming years.


Assuntos
Animais Exóticos , Fixação Interna de Fraturas/veterinária , Equipamentos Ortopédicos/veterinária , Ortopedia/veterinária , Animais , Aves , Pinos Ortopédicos/veterinária , Placas Ósseas/veterinária , Parafusos Ósseos/veterinária , Transplante Ósseo/veterinária , Fixação Interna de Fraturas/tendências , Fixação Intramedular de Fraturas/tendências , Fixação Intramedular de Fraturas/veterinária , Humanos , Mamíferos , Transplante de Células-Tronco Mesenquimais/veterinária , Equipamentos Ortopédicos/tendências , Ortopedia/métodos , Próteses e Implantes/veterinária , Répteis
13.
Egypt J Immunol ; 26(1): 55-67, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31332996

RESUMO

Diabetes Mellitus (D.M.) is a disease with a high and increasing prevalence. The Insulin- producing Cells (IPCs) derived from the Wharton's jelly of human umbilical cord transplantation was thought to be the most promising strategy for treating Diabetes. This study aimed to evaluate IPCs immune modulatory changes occurred after transplanted through two different routes and the effect of these changes on their therapeutic efficiency in relation to transplantation microenvironment. Insulin Producing Cells was induced to differentiate from human Umbilical Cord-Mesenchymal Stem Cells and characterized by morphology under phase contrast inverted microscope and staining of secretory granules by DTZ (diphenylthiocarbonazone) stain, then therapeutic effect was evaluated both in vitro and in vivo through glucose challenge test and hyperglycemia correction in STZ (streptozotocin)- induced diabetic rats. Immune-modulatory changes evaluated by cell- mediated lysis assay and Syber green quantification of immune inflammatory cytokines (IFN- , TGF- ß and IL-10) gene expression by real-time PCR. We observed that in spite of the weak immunogenicity of induced IPCs derived from HUC-MSCs in vitro, but when transplanted in vivo especially through the intra portal vein they could induce an immune response when interact with the disease microenvironment resulting in different degree of inflammatory response. Therefore, the relationship between disease microenvironment and immune alteration should be examined before transplantation therapy.


Assuntos
Diabetes Mellitus Experimental/imunologia , Insulinas , Transplante de Células-Tronco Mesenquimais , Geleia de Wharton/citologia , Animais , Diferenciação Celular , Citocinas/imunologia , Diabetes Mellitus Experimental/terapia , Humanos , Células-Tronco Mesenquimais/citologia , Ratos , Cordão Umbilical/citologia
14.
J Biol Regul Homeost Agents ; 33(4): 1019-1022, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347346

RESUMO

Mesenchymal stem cells (MSCs) are able to exert immunomodulatory and anti-inflammatory actions. Thanks to these properties, MSCs may be a promising alternative approach for the treatment of inflammatory disease. Important cytokines involved in inflammation are those included in the IL-1 family. Interleukin-37 (IL-37) is one of the member able to suppress both innate and adaptive immunity. Recently, it was found that MSCs and their derivatives can modulate IL-37, and MSCs expressing IL-37 seem to have an enhanced therapeutic efficacy.


Assuntos
Interleucina-1/fisiologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Citocinas , Humanos , Inflamação
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.
Cell Prolif ; 52(5): e12658, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31297910

RESUMO

OBJECTIVES: The bone tissue engineering primarily focuses on three-dimensional co-culture systems, which physical and biological properties resemble the cell matrix of actual tissues. The complex dialogue between bone-forming and endothelial cells (ECs) in a tissue-engineered construct will directly regulate angiogenesis and bone regeneration. The purpose of this study was to investigate whether co-culture between osteogenic and angiogenic cells derived by bone mesenchymal stem cells (MSCs) could affect cell activities and new bone formation. MATERIALS AND METHODS: Mesenchymal stem cells were dually induced to differentiate into osteogenic cells (OMSCs) and ECs; both cell types were co-cultured at different ratios to investigate their effects and underlying mechanisms through ELISA, RT-qPCR and MTT assays. The selected cell mixture was transplanted onto a nano-hydroxyapatite/polyurethane (n-HA/PU) scaffold to form a cell-scaffold construct that was implanted in the rat femoral condyles. Histology and micro-CT were examined for further verification. RESULTS: ELISA and gene expression studies revealed that co-cultured OMSCs/ECs (0.5/1.5) significantly elevated the transcription levels of osteogenic genes such as ALP, Col-I and OCN, as well as transcription factors Msx2, Runx2 and Osterix; it also upregulated angiogenic factors of vascular endothelial growth factor (VEGF) and CD31 when compared with cells cultured alone or in other ratios. The optimized OMSCs/ECs group had more abundant calcium phosphate crystal deposition, further facilitated their bone formation in vivo. CONCLUSIONS: The OMSCs/ECs-scaffold constructs at an optimal cell ratio (0.5/1.5) achieved enhanced osteogenic and angiogenic factor expression and biomineralization, which resulted in more effective bone formation.


Assuntos
Materiais Biomiméticos/química , Regeneração Óssea/fisiologia , Osso e Ossos/fisiologia , Células-Tronco Mesenquimais/citologia , Tecidos Suporte/química , Animais , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Diferenciação Celular , Células Cultivadas , Técnicas de Cocultura , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Durapatita/química , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Ratos , Ratos Sprague-Dawley , Engenharia Tecidual , Fatores de Transcrição/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
J Photochem Photobiol B ; 198: 111561, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352000

RESUMO

Blindness and vision loss contribute to irreversible retinal degeneration, and cellular therapy for retinal cell replacement has the potential to treat individuals who have lost light sensitive photoreceptors in the retina. Retinal cells are well characterized in function, and are a subject of interest in cellular replacement therapy of photoreceptors and the retinal pigment epithelium. However, retinal cell transplantation is limited by various factors, including the choice of potential stem cell source that can show variability in plasticity as well as host tissue integration. Dental pulp is one such source that contains an abundance of stem cells. In this study we used dental pulp-derived mesenchymal stem cells (DPSCs) to mitigate sodium iodate (NaIO3) insult in a rat model of retinal degeneration. Sprague-Dawley rats were first given an intravitreal injection of 3 × 105 DPSCs as well as a single systemic administration of NaIO3 (40 mg/kg). Electroretinography (ERG) was performed for the next two months and was followed-up by histological analysis. The ERG recordings showed protection of DPSC-treated retinas within 4 weeks, which was statistically significant (* P ≤ .05) compared to the control. Retinal thickness of the control was also found to be thinner (*** P ≤ .001). The DPSCs were found integrated in the photoreceptor layer through immunohistochemical staining. Our findings showed that DPSCs have the potential to moderate retinal degeneration. In conclusion, DPSCs are a potential source of stem cells in the field of eye stem cell therapy due to its protective effects against retinal degeneration.


Assuntos
Iodatos/toxicidade , Transplante de Células-Tronco Mesenquimais , Degeneração Retiniana/terapia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Polpa Dentária/citologia , Modelos Animais de Doenças , Eletrorretinografia , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Células Fotorreceptoras/citologia , Ratos , Ratos Sprague-Dawley , Degeneração Retiniana/etiologia , Epitélio Pigmentado da Retina/patologia
18.
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
19.
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
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(7): 619-623, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31315757

RESUMO

Bronchopulmonary dysplasia (BPD) is one of the most common chronic lung diseases in neonates especially in preterm infants. It is also the main reason leading to a poor prognosis. The prognosis of the neonates with BPD is unsatisfactory with current treatment strategies. Recent clinical trails have found that mesenchymal stem cell (MSC) transplantation might be effective and promising for treatment of BPD in neonates. This article outlines the characteristics of MSC and the potential mechanisms of MSC transplantation for BPD in vivo, and the safety and feasibility of MSC transplantation in BPD neonates, as well as the challenges in clinical trials on MSC transplantation for treatment of BPD.


Assuntos
Displasia Broncopulmonar , Transplante de Células-Tronco Mesenquimais , Displasia Broncopulmonar/terapia , Humanos , Recém-Nascido Prematuro
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