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1.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202508

RESUMO

When looking for the causes and treatments of infertility, much attention is paid to one of the reproductive tissues-the endometrium. Therefore, endometrial stem cells are an attractive target for infertility studies in women of unexplained origin. Menstrual blood stem cells (MenSCs) are morphologically and functionally similar to cells derived directly from the endometrium; with dual expression of mesenchymal and embryonic cell markers, they proliferate and regenerate better than bone marrow mesenchymal stem cells. In addition, menstrual blood stem cells are extracted in a non-invasive and painless manner. In our study, we analyzed the characteristics and the potential for decidualization of menstrual blood stem cells isolated from healthy volunteers and women diagnosed with infertility. We demonstrated that MenSCs express CD44, CD166, CD16, CD15, BMSC, CD56, CD13 and HLA-ABC surface markers, have proliferative properties, and after induction of menstrual stem cell differentiation into epithelial direction, expression of genes related to decidualization (PRL, ESR, IGFBP and FOXO1) and angiogenesis (HIF1, VEGFR2 and VEGFR3) increased. Additionally, the p53, p21, H3K27me3 and HyperAcH4 proteins' expression increased during MenSCs decidualization, they secrete proteins that are involved in the regulation of the actin cytoskeleton, estrogen and relaxin signaling pathways and the management of inflammatory processes. Our findings reveal the potential use of MenSCs for the treatment of reproductive disorders.


Assuntos
Endométrio/citologia , Infertilidade Feminina/terapia , Menstruação , Transplante de Células-Tronco , Células-Tronco/citologia , Células-Tronco/metabolismo , Biomarcadores , Diferenciação Celular , Proliferação de Células , Separação Celular/métodos , Células Cultivadas , Decídua/citologia , Decídua/metabolismo , Feminino , Humanos , Imunofenotipagem , Infertilidade Feminina/etiologia , Proteoma , Proteômica/métodos
2.
Chin Med J (Engl) ; 134(13): 1535-1545, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34250959

RESUMO

ABSTRACT: Chronic obstructive pulmonary disease (COPD), characterized by persistent and not fully reversible airflow restrictions, is currently one of the most widespread chronic lung diseases in the world. The most common symptoms of COPD are cough, expectoration, and exertional dyspnea. Although various strategies have been developed during the last few decades, current medical treatment for COPD only focuses on the relief of symptoms, and the reversal of lung function deterioration and improvement in patient's quality of life are very limited. Consequently, development of novel effective therapeutic strategies for COPD is urgently needed. Stem cells were known to differentiate into a variety of cell types and used to regenerate lung parenchyma and airway structures. Stem cell therapy is a promising therapeutic strategy that has the potential to restore the lung function and improve the quality of life in patients with COPD. This review summarizes the current state of knowledge regarding the clinical research on the treatment of COPD with mesenchymal stem cells (MSCs) and aims to update the understanding of the role of MSCs in COPD treatment, which may be helpful for developing effective therapeutic strategies in clinical settings.


Assuntos
Células-Tronco Mesenquimais , Doença Pulmonar Obstrutiva Crônica , Humanos , Pulmão , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida , Transplante de Células-Tronco
3.
Int J Mol Sci ; 22(11)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070266

RESUMO

The purpose of this work is to describe the use of Fibrin-Plasma Rich in Growth Factors (PRGF) membranes for the treatment of a rabbit alkali-burn lesion. For this purpose, an alkali-burn lesion was induced in 15 rabbits. A week later, clinical events were evaluated and rabbits were divided into five treatment groups: rabbits treated with medical treatment, with a fibrin-PRGF membrane cultured with autologous or heterologous rabbit Limbal Epithelial Progenitor Cells (LEPCs), with a fibrin-PRGF membrane in a Simple Limbal Epithelial Transplantation and with a fibrin-PRGF membrane without cultured LEPCs. After 40 days of follow-up, corneas were subjected to histochemical examination and immunostaining against corneal or conjunctival markers. Seven days after alkali-burn lesion, it was observed that rabbits showed opaque cornea, new blood vessels across the limbus penetrating the cornea and epithelial defects. At the end of the follow-up period, an improvement of the clinical parameters analyzed was observed in transplanted rabbits. However, only rabbits transplanted with cultured LEPCs were positive for corneal markers. Otherwise, rabbits in the other three groups showed positive staining against conjunctival markers. In conclusion, fibrin-PRGF membrane improved the chemically induced lesions. Nonetheless, only fibrin-PRGF membranes cultured with rabbit LEPCs were able to restore the corneal surface.


Assuntos
Queimaduras Químicas , Células Epiteliais , Queimaduras Oculares , Fibrina/farmacologia , Plasma , Transplante de Células-Tronco , Células-Tronco , Animais , Autoenxertos , Queimaduras Químicas/metabolismo , Queimaduras Químicas/patologia , Queimaduras Químicas/terapia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Células Epiteliais/transplante , Queimaduras Oculares/metabolismo , Queimaduras Oculares/patologia , Queimaduras Oculares/terapia , Limbo da Córnea/metabolismo , Limbo da Córnea/patologia , Coelhos , Células-Tronco/metabolismo , Células-Tronco/patologia
4.
Int J Mol Sci ; 22(11)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070902

RESUMO

FLT3-mutated acute myeloid leukemia accounts for around 30% of acute myeloid leukemia (AML). The mutation carried a poor prognosis until the rise of tyrosine kinase inhibitors (TKIs). New potent and specific inhibitors have successfully altered the course of the disease, increasing the complete response rate and the survival of patients with FLT3-mutated AML. The aim of this article is to review all the current knowledge on these game-changing drugs as well as the unsolved issues raised by their use for fit and unfit FLT3-mutated AML patients. To this end, we analyzed the results of phase I, II, III clinical trials evaluating FLT3-TKI both in the first-line, relapse monotherapy or in combination referenced in the PubMed, the American Society of Hematology, the European Hematology Association, and the Clinicaltrials.gov databases, as well as basic science reports on TKI resistance from the same databases. The review follows a chronological presentation of the different trials that allowed the development of first- and second-generation TKI and ends with a review of the current lines of evidence on leukemic blasts resistance mechanisms that allow them to escape TKI.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Leucemia Mieloide Aguda/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/genética , Ensaios Clínicos como Assunto , Bases de Dados Factuais , Expressão Gênica , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Mutação , Recidiva , Transplante de Células-Tronco/métodos , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Tirosina Quinase 3 Semelhante a fms/metabolismo
5.
In Vivo ; 35(4): 2379-2390, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182521

RESUMO

BACKGROUND/AIM: The prognosis of mature T and natural killer (NK) cell neoplasms still remains dismal, despite the advancements in the understanding of the heterogeneous features of these diseases. As allogeneic stem cell transplantation (alloSCT) is an attractive salvage option for relapsed/refractory patients, we conducted this study to identify those who might benefit the most from alloSCT. PATIENTS AND METHODS: This was a retrospective, single-center, longitudinal cohort study of patients who received alloSCT between December 2019 and January 2000. RESULTS: The median relapse-free survival and overall survival were 4.4 and 10.0 months, respectively. Disease control status at alloSCT and number of previous treatments were associated with survival outcomes. The conditioning intensity did not significantly alter survival. CONCLUSION: AlloSCT offers a cure chance for selected relapsed or refractory T and NK cell neoplasms, especially when used early and the disease is well controlled prior to transplantation.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Neoplasias , Humanos , Células Matadoras Naturais , Estudos Longitudinais , Estudos Retrospectivos , Transplante de Células-Tronco , Condicionamento Pré-Transplante
6.
Stem Cell Res Ther ; 12(1): 352, 2021 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-34147129

RESUMO

BACKGROUND: Hearing loss affects 25% of the population at ages 60-69 years. Loss of the hair cells of the inner ear commonly underlies deafness and once lost this cell type cannot spontaneously regenerate in higher vertebrates. As a result, there is a need for the development of regenerative strategies to replace hair cells once lost. Stem cell-based therapies are one such strategy and offer promise for cell replacement in a variety of tissues. A number of investigators have previously demonstrated successful implantation, and certain level of regeneration of hair and supporting cells in both avian and mammalian models using rodent pluripotent stem cells. However, the ability of human stem cells to engraft and generate differentiated cell types in the inner ear is not well understood. METHODS: We differentiate human pluripotent stem cells to the pre-placodal stage in vitro then transplant them into the mouse cochlea after selective and complete lesioning of the endogenous population of hair cells. RESULTS: We demonstrate that hair cell ablation prior to transplantation leads to increased engraftment in the auditory sensory epithelium, the organ of Corti, as well as differentiation of transplanted cells into hair and supporting cell immunophenotypes. CONCLUSION: We have demonstrated the feasibility of human stem cell engraftment into an ablated mouse organ of Corti.


Assuntos
Células-Tronco Embrionárias Humanas , Células-Tronco Pluripotentes , Animais , Diferenciação Celular , Cóclea , Células Ciliadas Auditivas , Humanos , Camundongos , Transplante de Células-Tronco
7.
Life Sci ; 280: 119728, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34144057

RESUMO

AIMS: Progenitor cells-based regenerative strategy has shown promise to repair cartilage, an avascular tissue in which cells experience hypoxia. Hypoxia is known to improve the early chondrogenic differentiation of stem cells. Therefore, this study aimed to determine whether hypoxia preconditioning could be used to enhance the regenerative potential of the combination of buccal fat pad stem cells (BFPSCs) and bilayer chitosan-based hydrogel scaffold for articular cartilage repair. MATERIALS AND METHODS: Human BFPSCs were seeded on the bilayer chitosan-based hydrogel scaffolds in the culture medium. The viability and proliferation of cells on the scaffolds were monitored using scanning electron microscopy (SEM), MTT assay, and DAPI staining. Hypoxia preconditioned BFPSCs-seeded scaffolds were transplanted into rabbit articular cartilage knee defects for 12 weeks. The newly formed tissue was evaluated by cartilage-specific immunohistological analysis and histological staining. KEY FINDINGS: It was found that the chondrogenic differentiation and osteochondral conjunction in articular cartilage defect via BFPSCs-seeded bilayer scaffolds was enhanced by hypoxic preconditioning compared to a normoxic environment. SIGNIFICANCE: Based on our study, the integrity with subchondral bone in osteochondral defect was enhanced by BFPSCs on bilayer scaffold. Thus, this study provides evidence on the design of preconditioned cell-seeded bilayer hydrogels for articular cartilage regeneration.


Assuntos
Cartilagem Articular/citologia , Quitosana/química , Oxigênio/metabolismo , Transplante de Células-Tronco , Células-Tronco/citologia , Tecidos Suporte/química , Animais , Cartilagem Articular/fisiologia , Hipóxia Celular , Células Cultivadas , Condrogênese , Humanos , Masculino , Coelhos , Células-Tronco/metabolismo , Engenharia Tecidual/métodos
8.
FASEB J ; 35(7): e21709, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34143518

RESUMO

Tissues undergo a process of degeneration as the body ages. Mesenchymal stem cells (MSCs) have been found to have major potential in delaying the aging process in tissues and organs. However, the mechanism underlying the anti-aging effects of MSC is not clear which limits clinical applications. In this study, we used adipose-derived mesenchymal stem cells (ADSCs) to perform anti-aging treatments on senescent cells and progeroid animal models. Following intervention with ADSCs, replicative senescence was delayed and metabolic homeostasis was transformed from catabolism to anabolism. Metabolomic tests were used to analyze different metabolites. We found that ADSCs acted to accelerate mitophagy which eliminated intracellular ROS and improved the quality of mitochondria. These processes acted to regulate the cellular metabolic homeostasis and ultimately delayed the process of aging. Allogeneic stem cell therapy in a Progeria animal model (DNA polymerase gamma (POLG) knockin, mitochondrial dysfunction) also showed that ADSC therapy can improve alopecia and kyphosis by promoting mitophagy. Our research confirms for the first time that allogeneic stem cell therapy can improve aging-related symbols and phenotypes through mitochondrial quality control. These results are highly significant for the future applications of stem cells in aging-related diseases.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Envelhecimento/metabolismo , Homeostase/fisiologia , Mitofagia/fisiologia , Células-Tronco/metabolismo , Animais , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Senescência Celular/fisiologia , Modelos Animais de Doenças , Feminino , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Células-Tronco/métodos
9.
Int J Mol Sci ; 22(9)2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-34063721

RESUMO

Neuropathic pain (NP) is a complex, debilitating, chronic pain state, heterogeneous in nature and caused by a lesion or disease affecting the somatosensory system. Its pathogenesis involves a wide range of molecular pathways. NP treatment is extremely challenging, due to its complex underlying disease mechanisms. Current pharmacological and nonpharmacological approaches can provide long-lasting pain relief to a limited percentage of patients and lack safe and effective treatment options. Therefore, scientists are focusing on the introduction of novel treatment approaches, such as stem cell therapy. A growing number of reports have highlighted the potential of stem cells for treating NP. In this review, we briefly introduce NP, current pharmacological and nonpharmacological treatments, and preclinical studies of stem cells to treat NP. In addition, we summarize stem cell mechanisms-including neuromodulation in treating NP. Literature searches were conducted using PubMed to provide an overview of the neuroprotective effects of stem cells with particular emphasis on recent translational research regarding stem cell-based treatment of NP, highlighting its potential as a novel therapeutic approach.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Inflamação/terapia , Neuralgia/terapia , Transplante de Células-Tronco , Dor Crônica/patologia , Dor Crônica/terapia , Humanos , Inflamação/patologia , Neuralgia/patologia , Manejo da Dor , Células-Tronco/citologia
10.
Regen Med ; 16(6): 525-533, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34114493

RESUMO

Aim: There is a critical need for safe and effective treatments for COVID-19. One possible type of treatment is cellular medicine such as stem cell therapy, but its potential is unclear. Here, our aim was to assess the potential impact of the many cellular medicine trials for COVID-19. Materials & methods: We collected and analyzed data for defined criteria from trial registries. Results: Our data suggest that relatively few of these COVID-19 trials will produce high-level evidence, but that on average they may be somewhat more rigorous than typical cell therapy trials unrelated to COVID-19. Conclusion: Most COVID-19 cellular medicine trials have relatively low potential for rapid, concrete impact. We discuss the findings in the context of the cellular medicine field overall.


Assuntos
COVID-19 , SARS-CoV-2 , Transplante de Células-Tronco , Células-Tronco , Ensaios Clínicos como Assunto , Humanos
11.
BMJ ; 373: n955, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162530

RESUMO

Regenerative medicine aspires to transform the future practice of medicine by providing curative, rather than palliative, treatments. Healing the central nervous system (CNS) remains among regenerative medicine's most highly prized but formidable challenges. "Regenerative neurosurgery" provides access to the CNS or its surrounding structures to preserve or restore neurological function. Pioneering efforts over the past three decades have introduced cells, neurotrophins, and genes with putative regenerative capacity into the CNS to combat neurodegenerative, ischemic, and traumatic diseases. In this review we critically evaluate the rationale, paradigms, and translational progress of regenerative neurosurgery, harnessing access to the CNS to protect, rejuvenate, or replace cell types otherwise irreversibly compromised by neurological disease. We discuss the evidence surrounding fetal, somatic, and pluripotent stem cell derived implants to replace endogenous neuronal and glial cell types and provide trophic support. Neurotrophin based strategies via infusions and gene therapy highlight the motivation to preserve neuronal circuits, the complex fidelity of which cannot be readily recreated. We specifically highlight ongoing translational efforts in Parkinson's disease, amyotrophic lateral sclerosis, stroke, and spinal cord injury, using these to illustrate the principles, challenges, and opportunities of regenerative neurosurgery. Risks of associated procedures and novel neurosurgical trials are discussed, together with the ethical challenges they pose. After decades of efforts to develop and refine necessary tools and methodologies, regenerative neurosurgery is well positioned to advance treatments for refractory neurological diseases. Strategic multidisciplinary efforts will be critical to harness complementary technologies and maximize mechanistic feedback, accelerating iterative progress toward cures for neurological diseases.


Assuntos
Doenças do Sistema Nervoso/cirurgia , Medicina Regenerativa/métodos , Animais , Terapia Genética/métodos , Humanos , Neurocirurgia/métodos , Medicina Regenerativa/tendências , Transplante de Células-Tronco/métodos
12.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066067

RESUMO

Over the years, transfusion medicine has developed into a broad, multidisciplinary field that covers different clinical patient services such as apheresis technology and the development of stem cell transplantation. Recently, the discipline has found a niche in development and production of advanced therapy medicinal products (ATMPs) for immunotherapy and regenerative medicine purposes. In clinical trials, cell-based immunotherapies have shown encouraging results in the treatment of multiple cancers and autoimmune diseases. However, there are many parameters such as safety, a high level of specificity, and long-lasting efficacy that still need to be optimized to maximize the potential of cell-based immunotherapies. Thus, only a few have gained FDA approval, while the majority of them are studied in the context of investigator-initiated trials (IITs), where modern, academically oriented transfusion centers can play an important role. In this review, we summarize existing and contemporary cellular immunotherapies, which are already a part of modern transfusion medicine or are likely to become so in the future.


Assuntos
Imunoterapia/métodos , Neoplasias/terapia , Medicina Regenerativa , Transplante de Células-Tronco/métodos , Medicina Transfusional/métodos , Humanos
13.
Cell Prolif ; 54(6): e13046, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33960563

RESUMO

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible lung tissue damage including chronic bronchitis and emphysema, which could further develop into respiratory failure. Many studies have revealed a potential regenerative function of the distal airway stem/progenitor cells (DASCs) after lung injury. MATERIALS AND METHODS: Mouse and human DASCs were expanded, analysed, and engrafted into injured mouse lungs. Single-cell analyses were performed to reveal the differentiation path of the engrafted cells. Finally, human DASCs were transplanted into COPD mice induced by porcine pancreatic elastase (PPE) and lipopolysaccharide (LPS) administration. RESULTS: We showed that isolated mouse and human DASCs could be indefinitely expanded and were able to further differentiate into mature alveolar structures in vitro. Single-cell analysis indicated that the engrafted cells expressed typical cellular markers of type I alveolar cells as well as the specific secreted proteins. Interestingly, transplantation of human DASCs derived from COPD patients into the lungs of NOD-SCID mice with COPD injury repaired the tissue damage and improved the pulmonary function. CONCLUSIONS: The findings demonstrated that functional lung structure could be reconstituted by intrapulmonary transplantation of DASCs, suggesting a potential therapeutic role of DASCs transplantation in treatment for chronic obstructive pulmonary disease.


Assuntos
Pulmão/metabolismo , Doença Pulmonar Obstrutiva Crônica/terapia , Transplante de Células-Tronco , Células-Tronco/metabolismo , Animais , Feminino , Xenoenxertos , Humanos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Células-Tronco/patologia
14.
Nat Commun ; 12(1): 2901, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006870

RESUMO

Proliferative chronic myelomonocytic leukemia (pCMML), an aggressive CMML subtype, is associated with dismal outcomes. RAS pathway mutations, mainly NRASG12D, define the pCMML phenotype as demonstrated by our exome sequencing, progenitor colony assays and a Vav-Cre-NrasG12D mouse model. Further, these mutations promote CMML transformation to acute myeloid leukemia. Using a multiomics platform and biochemical and molecular studies we show that in pCMML RAS pathway mutations are associated with a unique gene expression profile enriched in mitotic kinases such as polo-like kinase 1 (PLK1). PLK1 transcript levels are shown to be regulated by an unmutated lysine methyl-transferase (KMT2A) resulting in increased promoter monomethylation of lysine 4 of histone 3. Pharmacologic inhibition of PLK1 in RAS mutant patient-derived xenografts, demonstrates the utility of personalized biomarker-driven therapeutics in pCMML.


Assuntos
Proteínas de Ciclo Celular/genética , GTP Fosfo-Hidrolases/genética , Histona-Lisina N-Metiltransferase/genética , Leucemia Mielomonocítica Crônica/genética , Proteínas de Membrana/genética , Mutação , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Animais , Proteínas de Ciclo Celular/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação Leucêmica da Expressão Gênica , Histona-Lisina N-Metiltransferase/metabolismo , Estimativa de Kaplan-Meier , Leucemia Mielomonocítica Crônica/metabolismo , Leucemia Mielomonocítica Crônica/terapia , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Proteína de Leucina Linfoide-Mieloide/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais/genética , Transplante de Células-Tronco/métodos , Transplante Homólogo , Sequenciamento Completo do Exoma/métodos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
15.
Aging (Albany NY) ; 13(10): 14399-14415, 2021 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-34031263

RESUMO

BACKGROUND: Cavernosa injury is a common cause of organic erectile dysfunction (ED), which requires safe and effective treatments. In the present study, the therapeutic efficiency of muscle-derived stem cells (MDSCs) modified with microRNA-126 (miR-126) was determined in rats with cavernosa injury. METHODS: MDSCs were transfected with miR-126 and then were transplanted into rats with cavernosa injury. Erectile function, vascular function (western blot and immunofluorescence), extraction, and detection of exosomes were then undertaken. RESULTS: On the 28th day after transplantation, the highest value of intra-cavernous pressure (ICP)/mean arterial pressure (MAP) in rats of miRNA-126 group (0.84 ± 0.14) was observed (Control: 0.38 ± 0.07; MDSC: 0.54 ± 0.11, Vector: 0.60 ± 0.02; respectively). Treatment of miRNA-126-modified-MDSCs remarkably strengthened vascular structure, supported by hematoxylin-eosin staining. The expression of CD31, von Willebrand Factor and vascular endothelial factors were higher than those in other groups, indicating improved vascular function. In vitro mechanism studies showed that exosomes containing miR-126 isolated from MDSCs promoted angiogenesis and attenuated apoptosis of human umbilical venous endothelial cells. Finally, insulin receptor substrate 1 and Krüppel-like factor 10 were determined as the direct target genes of miR-126. CONCLUSIONS: MiR-126 engineered MDSCs notably repaired cavernosa injury in rats via vascular reconstruction by directly targeting IRS1 and KLF10, in which the exosomes secreted by MDSCs played a critical role.


Assuntos
Engenharia Celular , Disfunção Erétil/etiologia , Disfunção Erétil/terapia , MicroRNAs/metabolismo , Músculos/patologia , Pênis/lesões , Transplante de Células-Tronco , Células-Tronco/metabolismo , Animais , Apoptose , Sequência de Bases , Proteínas de Ligação a DNA/metabolismo , Disfunção Erétil/genética , Exossomos/metabolismo , Exossomos/ultraestrutura , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Neovascularização Fisiológica , Pênis/irrigação sanguínea , Ratos Sprague-Dawley , Fatores de Transcrição/metabolismo
16.
Res Vet Sci ; 137: 127-137, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33965833

RESUMO

Rhesus macaque (Macaca mulatta) is widely applied in animal model construction of infertility, spermatogonia stem cell transplantation and male reproductive diseases. In this review, we describe the seasonal changes of the reproductive system in rhesus macaques, the regular pattern of spermatogenesis and spermatozoa maturation, and the differentiation of spermatogonia and spermatocytes. The duration of the M. mulatta spermatogenesis is approximately 10 days and seminiferous epithelium cycles mainly consist of 12 stages, which provide a suitable model for reproductive studies in non-human primates. Here, we summarize the features of gonadal development and sperm maturation in the rhesus monkeys, which provide important information in the studies of reproductive biology. Rhesus macaque is an excellent animal model in spermatogonia stem cell transplantation. We discuss the applications and progresses of assisted reproductive technologies in sperm liquefaction, semen cryopreservation and spermatogonia stem cell transplantation of rhesus macaques. Besides, we sort out recent proteomic analyses of male reproductive systems and semen samples in rhesus macaques. This review mainly focuses on male reproductive biology and application studies using M. mulatta, which would promote the development of new therapeutic interventions on assisted reproduction and reproductive disease studies in the future.


Assuntos
Genitália Masculina/fisiologia , Macaca mulatta/fisiologia , Espermatogênese , Espermatogônias/transplante , Transplante de Células-Tronco/veterinária , Animais , Criopreservação/veterinária , Masculino , Proteômica , Estações do Ano , Espermatozoides , Testículo/citologia
17.
Curr Cardiol Rep ; 23(6): 72, 2021 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-34050853

RESUMO

PURPOSE OF REVIEW: Cardiac cell-based therapy represents a promising approach for cardiac repair. However, one of the main challenges is cardiac arrhythmias associated with stem cell transplantation. The current review summarizes the recent progress in model systems for addressing mechanisms of arrhythmogenesis in cardiac repair. RECENT FINDINGS: Animal models have been extensively developed for mechanistic studies of cardiac arrhythmogenesis. Advances in human induced pluripotent stem cells (hiPSCs), patient-specific disease models, tissue engineering, and gene editing have greatly enhanced our ability to probe the mechanistic bases of cardiac arrhythmias. Additionally, recent development in multiscale computational studies and machine learning provides yet another powerful tool to quantitatively decipher the mechanisms of cardiac arrhythmias. Advancing efforts towards the integrations of experimental and computational studies are critical to gain insights into novel mitigation strategies for cardiac arrhythmias in cell-based therapy.


Assuntos
Células-Tronco Pluripotentes Induzidas , Animais , Arritmias Cardíacas , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Miócitos Cardíacos , Transplante de Células-Tronco
19.
BMC Womens Health ; 21(1): 184, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933047

RESUMO

BACKGROUND: Myeloid sarcoma (MS) is a very rare condition, develops both in patients with other hematological neoplasms, and as isolated tumor. MS of the gynecologic tract is extremely rare. An available literature data about diagnosis and management of MS is summarized in the article. The role of chemotherapy, radiation therapy, surgery and bone marrow transplantation in the treatment is discussed. Polychemotherapy and allogeneic bone marrow transplantation were suggested to be the optimal treatment strategy of MS of the gynecological tract. The use of new targeted agents results in promising clinical data. CASE PRESENTATION: We are presenting a rare clinical case of a MS of the uterine cervix with concomitant bone marrow involvement and describe all the peculiarities of the clinical course, diagnosis, and treatment. The patient received chemotherapy followed by allogeneic bone marrow transplantation. The pre-transplant therapy allowed us to perform allogeneic bone marrow transplantation with the deepest response possible: complete PET-negative and MRD-negative remission of the disease. CONCLUSIONS: MS remains a subject of discussion regarding its diagnostic and therapeutic aspects. The use of novel targeting agents can be perspective option for patient with extramedullary disease.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Sarcoma Mieloide , Compostos Bicíclicos Heterocíclicos com Pontes , Feminino , Humanos , Sarcoma Mieloide/tratamento farmacológico , Transplante de Células-Tronco , Sulfonamidas
20.
Stem Cell Res Ther ; 12(1): 259, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933149

RESUMO

OBJECTIVE: To report the clinical outcomes of a novel surgical technique, namely simple limbal epithelial transplantation (SLET), for the treatment of limbal stem cell deficiency (LSCD). METHODS: Thirteen patients (13 eyes) with LSCD who underwent autologous (10 eyes) or allogeneic (3 eyes) modified SLET between 2018 and 2021 were enrolled in this study. Grades of symblepharon, corneal conjunctivalization, vascularization, opacification, and visual acuity (VA) were evaluated preoperatively and postoperatively. In 2 cases, in vivo confocal microscopy (IVCM) and impression cytology (IC) were performed to assess the proliferation and degeneration of limbal tissue. RESULTS: At a postoperative follow-up of 6.5±5.3 (range, 2-20) months, 10 (10/13, 76.92%) eyes maintained a successful outcome. The grades of symblepharon, corneal conjunctivalization, vascularization, and opacification were significantly improved after SLET (P<0.05). Two-line improvement in VA was found in 6 (6/10, 60%) eyes of the successful cases. Recurrence of LSCD occurred in 3 (3/13, 23.08%) eyes, and conjunctival cyst occurred in 1 patient. After SLET, the morphology and structure of corneal epithelial cells and epithelial transition around the limbal tissue fragments were detected by IVCM and IC. CONCLUSIONS: Our findings suggest that the SLET is a safe and effective technique for the treatment of LSCD. The corneal stroma and hAM can provide protection and nutrition for the limbal stem cells (LSCs) without negatively influencing the clinical outcomes. IVCM and IC after SLET can evaluate the effectiveness of surgery and the transition of LSCs and corneal epithelial cells.


Assuntos
Doenças da Córnea , Epitélio Corneano , Limbo da Córnea , China , Doenças da Córnea/cirurgia , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco , Células-Tronco , Transplante Autólogo
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