scholarly journals Roles and Mechanisms of Irisin in Attenuating Pathological Features of Osteoarthritis

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiangfen Li ◽  
Xiaofang Zhu ◽  
Hongle Wu ◽  
Thomas E. Van Dyke ◽  
Xiaoyang Xu ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Therapeutic Potential ◽  
Gene Knockout ◽  
Inflammatory Factors ◽  
Proliferative Potential ◽  
Opposite Pattern ◽  
Tissue Samples ◽  
Primary Chondrocytes ◽  
Cartilage Development

To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage development, osteoarthritis (OA) pathophysiology and its therapeutic potential for treating OA we applied the following five strategical analyses using (1) murine joint tissues at different developmental stages; (2) human normal and OA pathological tissue samples; (3) experimental OA mouse model; (4) irisin gene knockout (KO) and knock in (KI) mouse lines and their cartilage cells; (5) in vitro mechanistic experiments. We found that Irisin was involved in all stages of cartilage development. Both human and mouse OA tissues showed a decreased expression of irisin. Intra-articular injection of irisin attenuated ACLT-induced OA progression. Irisin knockout mice developed severe OA while irisin overexpression in both irisin KI mice and intraarticular injection of irisin protein attenuated OA progression. Irisin inhibited inflammation and promoted anabolism in chondrogenic ADTC5 cells. Proliferative potential of primary chondrocytes from KI mice was found to be enhanced, while KO mice showed an inhibition under normal or inflammatory conditions. The primary chondrocytes from irisin KI mice showed reduced expression of inflammatory factors and the chondrocytes isolated from KO mice showed an opposite pattern. In conclusion, it is the first time to show that irisin is involved in cartilage development and OA pathogenesis. Irisin has the potential to ameliorate OA progression by decreasing cartilage degradation and inhibiting inflammation, which could lead to the development of a novel therapeutic target for treating bone and cartilage disorders including osteoarthritis.

Stem Cells Derived from Human Exfoliated Deciduous teeth [shed] in Neuronal Disorders: A Review

2020 ◽  
Vol 16 ◽  
Author(s):  
Minu Anoop ◽  
Indrani Datta
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Dental Pulp ◽  
Therapeutic Potential ◽  
Permanent Teeth ◽  
Deciduous Teeth ◽  
Proliferative Potential ◽  
Pulp Tissue ◽  
Human Exfoliated Deciduous Teeth

: Most conventional treatments for neurodegenerative diseases fail due to their focus on neuroprotection rather than neurorestoration. Stem cell‐based therapies are becoming a potential treatment option for neurodegenerative diseases as they can home in, engraft, differentiate and produce factors for CNS recovery. Stem cells derived from human dental pulp tissue differ from other sources of mesenchymal stem cells due to their embryonic neural crest origin and neurotrophic property. These include both dental pulp stem cells [DPSCs] from dental pulp tissues of human permanent teeth and stem cells from human exfoliated deciduous teeth [SHED]. SHED offer many advantages over other types of MSCs such as good proliferative potential, minimal invasive procurement, neuronal differentiation and neurotrophic capacity, and negligible ethical concerns. The therapeutic potential of SHED is attributed to the paracrine action of extracellularly released secreted factors, specifically the secretome, of which exosomes is a key component. SHED and its conditioned media can be effective in neurodegeneration through multiple mechanisms, including cell replacement, paracrine effects, angiogenesis, synaptogenesis, immunomodulation, and apoptosis inhibition, and SHED exosomes offer an ideal refined bed-to-bench formulation in neurodegenerative disorders. However, in spite of these advantages, there are still some limitations of SHED exosome therapy, such as the effectiveness of long-term storage of SHED and their exosomes, the development of a robust GMP-grade manufacturing protocol, optimization of the route of administration, and evaluation of the efficacy and safety in humans. In this review, we have addressed the isolation, collection and properties of SHED along with its therapeutic potential on in vitro and in vivo neuronal disorder models as evident from the published literature.

scholarly journals The Inflammatory Role of Pro-Resolving Mediators in Endometriosis: An Integrative Review

2021 ◽  
Vol 22 (9) ◽  
pp. 4370
Author(s):  
Cássia de Fáveri ◽  
Paula M. Poeta Fermino ◽  
Anna P. Piovezan ◽  
Lia K. Volpato
Keyword(s):  
Intracellular Signaling ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Integrative Review ◽  
Inflammatory Factors ◽  
Resolvin D1 ◽  
Endogenous Factors

The pathogenesis of endometriosis is still controversial, although it is known that the inflammatory immune response plays a critical role in this process. The resolution of inflammation is an active process where the activation of endogenous factors allows the host tissue to maintain homeostasis. The mechanisms by which pro-resolving mediators (PRM) act in endometriosis are still little explored. Thus, this integrative review aims to synthesize the available content regarding the role of PRM in endometriosis. Experimental and in vitro studies with Lipoxin A4 demonstrate a potential inhibitory effect on endometrial lesions’ progression, attenuating pro-inflammatory and angiogenic signals, inhibiting proliferative and invasive action suppressing intracellular signaling induced by cytokines and estradiol, mainly through the FPR2/ALX. Investigations with Resolvin D1 demonstrated the inhibition of endometrial lesions and decreased pro-inflammatory factors. Annexin A1 is expressed in the endometrium and is specifically present in women with endometriosis, although the available studies are still inconsistent. Thus, we believe there is a gap in knowledge regarding the PRM pathways in patients with endometriosis. It is important to note that these substances’ therapeutic potential is evident since the immune and abnormal inflammatory responses play an essential role in endometriosis development and progression.

scholarly journals Human menstrual blood-derived stem cells mitigate bleomycin-induced pulmonary fibrosis through anti-apoptosis and anti-inflammatory effects

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Chen ◽  
Yi Wu ◽  
Yanling Wang ◽  
Lijun Chen ◽  
Wendi Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pulmonary Fibrosis ◽  
Therapeutic Potential ◽  
Lung Fibroblasts ◽  
Menstrual Blood ◽  
Inflammatory Factors ◽  
Mouse Lung ◽  
Control Group ◽  
Antibody Array

Abstract Background Idiopathic pulmonary fibrosis is a kind of diffuse interstitial lung disease, the pathogenesis of which is unclear, and there is currently a lack of good treatment to improve the survival rate. Human menstrual blood-derived mesenchymal stem cells (MenSCs) have shown great potential in regenerative medicine. This study aimed to explore the therapeutic potential of MenSCs for bleomycin-induced pulmonary fibrosis. Methods We investigated the transplantation of MenSCs in a pulmonary fibrosis mouse model induced by BLM. Mouse was divided into three groups: control group, BLM group, MenSC group. Twenty-one days after MenSC transplantation, we examined collagen content, pathological, fibrosis area in the lung tissue, and the level of inflammatory factors of serum. RNA sequence was used to examine the differential expressed gene between three groups. Transwell coculture experiments were further used to examine the function of MenSCs to MLE-12 cells and mouse lung fibroblasts (MLFs) in vitro. Results We observed that transplantation of MenSCs significantly improves pulmonary fibrosis mouse through evaluations of pathological lesions, collagen deposition, and inflammation. Transwell coculturing experiments showed that MenSCs suppress the proliferation and the differentiation of MLFs and inhibit the apoptosis of MLE-12 cells. Furthermore, antibody array results demonstrated that MenSCs inhibit the apoptosis of MLE-12 cells by suppressing the expression of inflammatory-related cytokines, including RANTES, Eotaxin, GM-CSF, MIP-1γ, MCP-5, CCL1, and GITR. Conclusions Collectively, our results suggested MenSCs have a great potential in the treatment of pulmonary fibrosis, and cytokines revealed in antibody array are expected to become the target of future therapy of MenSCs in clinical treatment of pulmonary fibrosis.

scholarly journals Characterization of the Hoechst 33342 side population from normal and malignant human renal epithelial cells

2008 ◽  
Vol 295 (3) ◽  
pp. F680-F687 ◽  
Author(s):  
Sanjai K. Addla ◽  
Mick D. Brown ◽  
Claire A. Hart ◽  
Vijay A. C. Ramani ◽  
Noel W. Clarke
Keyword(s):  
Stem Cell ◽  
Epithelial Cells ◽  
Side Population ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Proliferative Potential ◽  
Stem Cell Markers ◽  
Hoechst 33342 ◽  
Tissue Samples

The fundamental changes which predispose for renal cell carcinoma (RCC) are poorly characterized. It is hypothesized that “cancer stem cells” may be influential in carcinogenesis, and the epithelial side population (SP) is enriched for stemlike cells in other epithelial cancers. In this study, we have isolated and characterized the SP and non-SP (NSP) populations from normal (NK) and malignant (RCC) human kidney tissue. NK specimens were taken from patients undergoing non-renal cancer surgery and paired malignant and macroscopically normal tissue samples were taken from patients undergoing surgery for RCC. The Hoechst 33342 dye efflux technique was used to isolate epithelial SP and NSP from normal and malignant human renal tissue. Cellular subpopulations were phenotyped for lineage, cell cycle, and putative stem cell markers, and functionally characterized using in vitro colony-forming and proliferation assays. The SP constituted 3.8 ± 0.4 and 5.9 ± 0.9% of epithelial cells in NK and RCC, respectively, of which 14.1 ± 3.5 and 13.2 ± 3.6% were shown to be in G0. SP cells demonstrated greater proliferative potential in colony-forming efficiency, long-term culture, and spheroids assays and were shown to be maintained upon tissue culture passage. We have shown that the renal SP is enriched for quiescent cells, with a high proliferative capacity and stemlike properties. The population is, however, heterogeneous, confirming that the terms “SP cell” and “stem cell” cannot be used interchangeably.

scholarly journals A new and fast method to obtain in vitro cultures of Huperzia selago (Huperziaceae) sporophytes, a club moss which is a source of huperzine A

2013 ◽  
Vol 82 (4) ◽  
pp. 313-320 ◽  
Author(s):  
Wojciech J. Szypuła ◽  
Paulina Mistrzak ◽  
Olga Olszowska
Keyword(s):  
Developmental Stages ◽  
Therapeutic Potential ◽  
Callus Formation ◽  
Axenic Culture ◽  
Growth Index ◽  
In Vitro Cultures ◽  
Huperzine A ◽  
Fast Method ◽  
Biomass Growth

This study presents a protocol for a fast and effective in vitro axenic culture of <em>Huperzia selago</em> (Huperziaceae Rothm.) sporophytes, a club moss which is a source of huperzine A, an alkaloid of a considerable therapeutic potential extensively investigated for its uses as treatment for some neurodegenerative diseases. The proposed procedure allowed approximately tenfold shortening of the species developmental stages with the omission of the gametophyte stage while the sporophyte mass could be increased tenfold within a 6-month period. The cultures were established using vegetative propagules (bulbils) procured from sporophytes growing in the wild without degrading the habitats of this endangered plant species. Explants underwent surface and internal disinfection to eliminate the epiphytic and endophytic bacteria and fungi. In in vitro cultures, the optimum results were achieved using Moore (Mr) medium without growth regulators or supplemented with 0.015 mg/l IBA and 0.3 mg/l kinetin. These media ensured both viability of the propagules and their further development. The biomass growth index for <em>H. selago</em> sporophytes grown from propagules, determined at 3 months of culture (1 passage) on Mr medium with IBA and kinetin was 650%. At 6 months, the biomass growth index increased to 1114%. Vigorous growth of adventitious roots, especially on Mr medium with the addition of 0.25 mg/l NAA, and callus formation on shoot apices were observed. At 6 months of culture, some sporophytes obtained from the bulbils were used as the initiating material for shoot subcultures, which developed best on Mr medium with IBA and kinetin.

scholarly journals Self-organized emergence of hyaline cartilage in hiPSC-derived multi-tissue organoids

2021 ◽  
Author(s):  
Manci Li ◽  
Juan E. Abrahante ◽  
Amanda Vegoe ◽  
Yi Wen Chai ◽  
Beth Lindborg ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Lower Limb ◽  
Regulatory Networks ◽  
Hyaline Cartilage ◽  
Therapeutic Potential ◽  
Cartilage Growth ◽  
Cartilage Development ◽  
Self Organized

Despite holding great therapeutic potential, existing protocols for in vitro chondrogenesis and hyaline cartilage production from human induced pluripotent stem cells (hiPSC) are laborious and complex with unclear long-term consequences. Here, we developed a simple xeno- and feeder-free protocol for human hyaline cartilage production in vitro using hydrogel-cultured multi-tissue organoids (MTOs). We investigate gene regulatory networks during spontaneous hiPSC-MTO differentiation using RNA sequencing and bioinformatic analyses. We find the interplays between BMPs and neural FGF pathways are associated with the phenotype transition of MTOs. We recognize TGF-beta/BMP and Wnt signaling likely contribute to the long-term maintenance of MTO cartilage growth and further adoption of articular cartilage development. By comparing the MTO transcriptome with human lower limb chondrocytes, we observe that the expression of chondrocyte-specific genes in MTO shows a strong correlation with fetal lower limb chondrocytes. Collectively, our findings describe the self-organized emergence of hyaline cartilage in MTO, its associated molecular pathways, and its spontaneous adoption of articular cartilage development trajectory.

scholarly journals Cryopreserved fragments of testicular seminiferous tubules of rats as a source of spermatogonial stem cells

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
N. Volkova ◽  
◽  
M. Yukhta ◽  
L. Sokil ◽  
L. Chernyschenko ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Culture ◽  
Morphological Characteristics ◽  
Relative Number ◽  
Spermatogonial Stem Cells ◽  
Blue Staining ◽  
Seminiferous Tubules ◽  
Proliferative Potential ◽  
Tissue Samples

The use of modern technologies of cryopreservation of testicular tissue samples in prepubertal patients is one of the ways to maintain their fertility in the future. The purpose of the study was to investigate the proliferative potential, morphological characteristics and expression of specific markers of cell culture obtained from cryopreserved and vitrified fragments of seminiferous tubules (FSTs) of rats' testis. Materials and methods. The isolation of cells from native, cryopreserved and vitrified FSTs of immature rats was performed by incubation in a solution of collagenase type IV (1 mg/mL) + DNase (500 μg/mL). Cell viability was determined by Trypan blue staining. Monoclonal antibodies CD9-FITC, CD24-PE, CD45-FITC, CD90-FITC were used for immunophenotype analysis. Morphological characteristics, proliferative activity (MTT assay), relative number of cells positive for MAGE-B1 and vimentin were assessed in the obtained cultures. Results. The analysis of phenotypic characteristics showed that cells from native, cryopreserved and vitrified FSTs were characterized by high expression level of CD9 (≥ 40 %), CD24 (≥ 70 %), CD90 (≥ 70 %) and low expression of the CD45 (≤ 1 %). In cell culture in vitro, the studied cells from cryopreserved and vitrified rat's FSTs had the ability to adhere and proliferate while maintaining a cells population positive for MAGE-B1 and vimentin. Conclusions. The results can be the basis for the development of effective protocols for the cultivation and cryopreservation of testicular spermatogonial stem cells in order to restore fertility in men.

scholarly journals The Impact of CRISPR/Cas9 Technology on Cardiac Research: From Disease Modelling to Therapeutic Approaches

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Benedetta M. Motta ◽  
Peter P. Pramstaller ◽  
Andrew A. Hicks ◽  
Alessandra Rossini
Keyword(s):  
Genome Editing ◽  
Ethical Issues ◽  
Therapeutic Potential ◽  
Gene Knockout ◽  
Model Systems ◽  
Large Deletions ◽  
Induced Pluripotent ◽  
The Impact

Genome-editing technology has emerged as a powerful method that enables the generation of genetically modified cells and organisms necessary to elucidate gene function and mechanisms of human diseases. The clustered regularly interspaced short palindromic repeats- (CRISPR-) associated 9 (Cas9) system has rapidly become one of the most popular approaches for genome editing in basic biomedical research over recent years because of its simplicity and adaptability. CRISPR/Cas9 genome editing has been used to correct DNA mutations ranging from a single base pair to large deletions in both in vitro and in vivo model systems. CRISPR/Cas9 has been used to increase the understanding of many aspects of cardiovascular disorders, including lipid metabolism, electrophysiology and genetic inheritance. The CRISPR/Cas9 technology has been proven to be effective in creating gene knockout (KO) or knockin in human cells and is particularly useful for editing induced pluripotent stem cells (iPSCs). Despite these progresses, some biological, technical, and ethical issues are limiting the therapeutic potential of genome editing in cardiovascular diseases. This review will focus on various applications of CRISPR/Cas9 genome editing in the cardiovascular field, for both disease research and the prospect of in vivo genome-editing therapies in the future.

scholarly journals Imperatorin alleviated NLRP3 inflammasome cascade-induced synovial fibrosis and synovitis in rats with knee osteoarthritis

2021 ◽  
Author(s):  
Haosheng Zhang ◽  
Liang Ding ◽  
Xiaoqing Shi ◽  
Wei Mei ◽  
Zhengquan Huang ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Nlrp3 Inflammasome ◽  
Therapeutic Potential ◽  
Synovial Fibroblasts ◽  
Male Rats ◽  
Inflammatory Factors ◽  
Histopathological Analysis ◽  
Monosodium Iodoacetate ◽  
Synovial Tissues

Abstract Background: To clarify the therapeutic potential of imperatorin (IMP) in knee osteoarthritis (KOA).Methods: Thirty 3-month-old SD male rats were randomly divided into Normal group, monosodium iodoacetate (MIA) group and MIA+IMP group. Their synovial tissues were subjected to histopathological analysis. Primary synovial fibroblasts obtained from additional normal rats were treated by lipopolysaccharide (LPS) and then IMP. The mRNA and protein expressions of factors related to synovitis and synovial fibrosis were detected by qRT-PCR and Western blotting, respectively. The levels of inflammatory factors IL-1β and IL-18 were measured by ELISA.Results: IMP reduced HIF-1α, NLRP3 inflammasome expression and IL-1β, IL-18 production in synovial fibroblasts induced by LPS. IMP also down-regulated synovial fibrosis markers. In vitro study revealed that MIA-induced synovitis and synovial fibrosis were relieved by IMP.Conclusion: IMP exerts anti-inflammatory effects associated with synovitis and synovial fibrosis. It reduces the production of pro-inflammatory mediators and cytokines and inhibits TGF-β1, TIMP-1 and VEGF expressions that promote synovial fibrosis.

Correlated Studies of Cellular Interactions Using TEM, Freeze Etching, and SEM

1974 ◽  
Vol 32 ◽  
pp. 320-321
Author(s):  
J. P. Revel
Keyword(s):  
Developmental Stages ◽  
Three Dimensional ◽  
Cell Movement ◽  
Cellular Interactions ◽  
Serial Sections ◽  
Cell Sheets ◽  
Freeze Etching ◽  
Early Developmental

Movement of individual cells or of cell sheets and complex patterns of folding play a prominent role in the early developmental stages of the embryo. Our understanding of these processes is based on three- dimensional reconstructions laboriously prepared from serial sections, and from autoradiographic and other studies. Many concepts have also evolved from extrapolation of investigations of cell movement carried out in vitro. The scanning electron microscope now allows us to examine some of these events in situ. It is possible to prepare dissections of embryos and even of tissues of adult animals which reveal existing relationships between various structures more readily than used to be possible vithout an SEM.

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