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The Effect of Exosomes Derived from Unrestricted Somatic Stem Cells on Murine Model of Sepsis. 来自非限制性体细胞干细胞的外泌体对小鼠脓毒症模型的影响。
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 DOI: 10.1159/000520639
Mahshid Akhavan Rahnama, Mina Soufi Zomorrod, Saeid Abroun, Amir Atashi
{"title":"The Effect of Exosomes Derived from Unrestricted Somatic Stem Cells on Murine Model of Sepsis.","authors":"Mahshid Akhavan Rahnama,&nbsp;Mina Soufi Zomorrod,&nbsp;Saeid Abroun,&nbsp;Amir Atashi","doi":"10.1159/000520639","DOIUrl":"https://doi.org/10.1159/000520639","url":null,"abstract":"<p><p>Sepsis is a systemic infection mainly caused by bacterial infections. Despite all efforts and advances in the treatment of sepsis, it is still considered one of the leading causes of death in hospitalized patients. Today, we have to use novel therapies and one of the most important is cell-free therapy. Exosomes have been shown to contain the contents of their parent cells and that they do not generate an immune response between different individuals which makes them a good candidate for transplantation. Unrestricted somatic stem cells (USSC), also known as mesenchymal stem cell progenitors due to their high proliferative capacity and low immune response, may be a novel therapy for sepsis. In this study, the effect of USSC-derived exosomes on sepsis was investigated using a mouse model. USSCs were isolated from human cord blood and characterized by flow cytometry and multi-lineage differentiation. The exosomes were then harvested from USSCs and characterized by transmission electron microscopy, Western blotting, and dynamic light scattering. The harvested exosomes were injected into the mouse model of sepsis. Biochemical, histological, molecular, and survival studies were performed in different groups. Our observations showed that USSC-derived exosomes can reduce inflammation in septic mice. Histopathologic and biochemical findings in the sham group showed multiorgan involvement, but these changes disappeared after 7 days of exosome administration. Moreover, the expression of IRAK-1 and TRAF-6 (main adapter molecules in signaling pathways of inflammation) was decreased through negative regulation by miR-146a after 72 h of exosome administration. A 2-fold increase in the level of IL-10 and a 2-fold decrease in the levels of IL-6 and TNF-α was observed. In conclusion, we showed that direct injection of USSC-derived exosomes can be one of the important methods for the treatment of various aspects of sepsis due to their immunomodulatory properties.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9714881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Development of a High-Color Flow Cytometry Panel for Immunologic Analysis of Tissue Injury and Reconstruction in a Rat Model. 用于大鼠组织损伤和重建模型免疫分析的高彩色流式细胞仪面板的研制。
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 DOI: 10.1159/000524682
Kenneth M Adusei, Tran B Ngo, Andrea Lucia Alfonso, Ravi Lokwani, Sabrina DeStefano, Maria Karkanitsa, Jacquelyn Spathies, Stephen M Goldman, Christopher L Dearth, Kaitlyn Noelle Sadtler
{"title":"Development of a High-Color Flow Cytometry Panel for Immunologic Analysis of Tissue Injury and Reconstruction in a Rat Model.","authors":"Kenneth M Adusei,&nbsp;Tran B Ngo,&nbsp;Andrea Lucia Alfonso,&nbsp;Ravi Lokwani,&nbsp;Sabrina DeStefano,&nbsp;Maria Karkanitsa,&nbsp;Jacquelyn Spathies,&nbsp;Stephen M Goldman,&nbsp;Christopher L Dearth,&nbsp;Kaitlyn Noelle Sadtler","doi":"10.1159/000524682","DOIUrl":"https://doi.org/10.1159/000524682","url":null,"abstract":"<p><p>The rat model is an important resource in biomedical research due to its similarities to the human immune system and its use for functional studies. However, because of the preponderance of mouse models in foundational and mechanistic immunological studies, there is a relative lack of diverse, commercially available flow cytometry antibodies for immunological profiling in the rat model. Available antibodies are often conjugated to common fluorophores with similar peak emission wavelengths, making them hard to distinguish on conventional flow cytometers and restricting more comprehensive immune analysis. This can become a limitation when designing immunological studies in rat injury models to investigate the immune response to tissue injury. In addition, this lack of available antibodies limits the number of studies that can be done on the immune populations in lymphoid organs in other research areas. To address this critical unmet need, we designed a spectral flow cytometry panel for rat models. Spectral cytometry distinguishes between different fluorophores by capturing their full emission spectra instead of their peak emission wavelengths. This flow cytometry panel includes 24 distinct immune cell markers to analyze the innate and adaptive immune response. Importantly, this panel identifies different immune phenotypes, including tolerogenic, Type 1, and Type 2 immune responses. We show that this panel can identify unique immune populations and phenotypes in a rat muscle trauma model. We further validated that the panel can identify distinct adaptive and innate immune populations and their unique phenotypes in lymphoid organs. This panel expands the scope of previous rat panels providing a tool for scientists to examine the immune system in homeostasis and injury while pairing mechanistic immunological studies with functional studies.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9139105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Umbilical Cord Blood Cell Clearance Post-Infusion in Immune-Competent Children with Cerebral Palsy. 免疫功能正常的脑瘫患儿输注脐带血后的细胞清除。
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 Epub Date: 2022-10-19 DOI: 10.1159/000527612
Kylie Crompton, David E Godler, Ling Ling, Ngaire Elwood, Francoise Mechinaud-Heloury, Trisha Soosay Raj, Kuang-Chih Hsiao, Jacqueline Fleming, Karin Tiedemann, Iona Novak, Michael Fahey, Xiaofang Wang, Katherine J Lee, Paul B Colditz, Priya Edwards, Dinah Reddihough
{"title":"Umbilical Cord Blood Cell Clearance Post-Infusion in Immune-Competent Children with Cerebral Palsy.","authors":"Kylie Crompton, David E Godler, Ling Ling, Ngaire Elwood, Francoise Mechinaud-Heloury, Trisha Soosay Raj, Kuang-Chih Hsiao, Jacqueline Fleming, Karin Tiedemann, Iona Novak, Michael Fahey, Xiaofang Wang, Katherine J Lee, Paul B Colditz, Priya Edwards, Dinah Reddihough","doi":"10.1159/000527612","DOIUrl":"10.1159/000527612","url":null,"abstract":"<p><p>Umbilical cord blood cells have therapeutic potential for neurological disorders, through a paracrine mechanism of action. A greater understanding of the safety and immunological effects of allogeneic donor cord blood cells in the context of a healthy recipient immune system, such as in cerebral palsy, is needed. This study aimed to determine how quickly donor cord blood cells were cleared from the circulation in children with cerebral palsy who received a single intravenous infusion of 12/12 human leucocyte antigen (HLA)-matched sibling cord blood cells. Twelve participants with cerebral palsy aged 2-12 years received cord blood cell infusions as part of a phase I trial of umbilical blood infusion for cerebral palsy. Digital droplet PCR analysis of DNA copy number variants specific to donor and recipient was used to assess donor DNA clearance at five timepoints post-infusion, a surrogate measure of cell clearance. Donor cells were cleared by 3 months post-infusion in 11/12 participants. When detected, donor DNA was at a fraction of 0.01-0.31% of total DNA with no signs of graft-versus-host disease in any participant. The donor DNA clearance times provided by this study have important implications for understanding the safety of allogeneic cord blood cell infusion for cerebral palsy and translational tissue engineering or regenerative medicine research in other disorders.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40343533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Apoptosis-Decellularized Peripheral Nerve Scaffold Allows Regeneration across Nerve Gap. 凋亡去细胞化外周神经支架允许神经间隙再生
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 Epub Date: 2022-08-26 DOI: 10.1159/000525704
Rebecca A Wachs, Steven M Wellman, Stacy L Porvasnik, Emily H Lakes, R Chase Cornelison, Young Hye Song, Kyle D Allen, Christine E Schmidt
{"title":"Apoptosis-Decellularized Peripheral Nerve Scaffold Allows Regeneration across Nerve Gap.","authors":"Rebecca A Wachs, Steven M Wellman, Stacy L Porvasnik, Emily H Lakes, R Chase Cornelison, Young Hye Song, Kyle D Allen, Christine E Schmidt","doi":"10.1159/000525704","DOIUrl":"10.1159/000525704","url":null,"abstract":"<p><p>Peripheral nerve injury results in loss of motor and sensory function distal to the nerve injury and is often permanent in nerve gaps longer than 5 cm. Autologous nerve grafts (nerve autografts) utilize patients' own nerve tissue from another part of their body to repair the defect and are the gold standard in care. However, there is a limited autologous tissue supply, size mismatch between donor nerve and injured nerve, and morbidity at the site of nerve donation. Decellularized cadaveric nerve tissue alleviates some of these limitations and has demonstrated success clinically. We previously developed an alternative apoptosis-assisted decellularization process for nerve tissue. This new process may result in an ideal scaffold for peripheral nerve regeneration by gently removing cells and antigens while preserving delicate topographical cues. In addition, the apoptosis-assisted process requires less active processing time and is inexpensive. This study examines the utility of apoptosis-decellularized peripheral nerve scaffolds compared to detergent-decellularized peripheral nerve scaffolds and isograft controls in a rat nerve gap model. Results indicate that, at 8 weeks post-injury, apoptosis-decellularized peripheral nerve scaffolds perform similarly to detergent-decellularized and isograft controls in both functional (muscle weight recovery, gait analysis) and histological measures (neurofilament staining, macrophage infiltration). These new apoptosis-decellularized scaffolds hold great promise to provide a less expensive scaffold for nerve injury repair, with the potential to improve nerve regeneration and functional outcomes compared to current detergent-decellularized scaffolds.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40422021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Organoids in the Clinic: A Systematic Review of Outcomes. 临床中的器官组织:成果系统回顾。
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 Epub Date: 2022-09-28 DOI: 10.1159/000527237
Bjørn Hofmann, Severin Zinöcker, Søren Holm, Jonathan Lewis, Panagiotis Kavouras
{"title":"Organoids in the Clinic: A Systematic Review of Outcomes.","authors":"Bjørn Hofmann, Severin Zinöcker, Søren Holm, Jonathan Lewis, Panagiotis Kavouras","doi":"10.1159/000527237","DOIUrl":"10.1159/000527237","url":null,"abstract":"<p><p>Research on organoids has undergone significant advances during the last decade. However, outcomes from the use of organoids in clinical trials have not yet been documented. Therefore, there is an urgent need to assess the reporting of clinically relevant outcomes from organoid research in the scientific literature. This article presents a systematic review and appraisal of the published literature in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, together with a synopsis of recent relevant reviews. Surprisingly, no randomized controlled trials have reported clinical outcomes with any types of organoids. We found very few ongoing and registered studies that may provide clinically relevant results within this decade. Our screening and interpretation of the literature, including review articles, indicate a focus on technical and preclinical aspects of organoid research. This is the first systematic review of clinical trials involving organoids. Few clinical studies are planned or already underway, and, so far, no high-quality evidence relating to the clinical outcomes of organoid research has been published. The many promises of organoid research still need to be translated from bench to bed.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10906541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40380298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Tunable Calcium Phosphate Coating to Drive in vivo Osseointegration of Composite Engineered Tissues. 一种可调磷酸钙涂层,用于驱动复合工程组织的体内骨整合。
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 Epub Date: 2023-03-24 DOI: 10.1159/000528965
Matthew Fainor, Sonal Mahindroo, Kerri R Betz, Janai Augustin, Harvey E Smith, Robert L Mauck, Sarah E Gullbrand
{"title":"A Tunable Calcium Phosphate Coating to Drive in vivo Osseointegration of Composite Engineered Tissues.","authors":"Matthew Fainor, Sonal Mahindroo, Kerri R Betz, Janai Augustin, Harvey E Smith, Robert L Mauck, Sarah E Gullbrand","doi":"10.1159/000528965","DOIUrl":"10.1159/000528965","url":null,"abstract":"<p><p>Varying degrees of hydroxyapatite (HA) surface functionalization have been implicated as the primary driver of differential osteogenesis observed in infiltrating cells. The ability to reliably create spatially controlled areas of mineralization in composite engineered tissues is of growing interest in the field, and the use of HA-functionalized biomaterials may provide a robust solution to this challenge. In this study, we successfully fabricated polycaprolactone salt-leached scaffolds with two levels of a biomimetic calcium phosphate coating to examine their effects on MSC osteogenesis. Longer duration coating in simulated body fluid (SBF) led to increased HA crystal nucleation within scaffold interiors as well as more robust HA crystal formation on scaffold surfaces. Ultimately, the increased surface stiffness of scaffolds coated in SBF for 7 days in comparison to scaffolds coated in SBF for 1 day led to more robust osteogenesis of MSCs in vitro without the assistance of osteogenic signaling molecules. This study also demonstrated that the use of SBF-based HA coatings can promote higher levels of osteogenesis in vivo. Finally, when incorporated as the endplate region of a larger tissue-engineered intervertebral disc replacement, HA coating did not induce mineralization in or promote cell migration out of neighboring biomaterials. Overall, these results verified tunable biomimetic HA coatings as a promising biomaterial modification to promote discrete regions of mineralization within composite engineered tissues.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9174881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lentivirus-shRNA Mediated Prolyl Hydroxylase 2 Knockdown Increases HIF-1α and Inhibits Nucleus Pulposus Cells Degeneration. 慢病毒- shrna介导的脯氨酸羟化酶2敲低增加HIF-1α并抑制髓核细胞变性
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 DOI: 10.1159/000520795
Qi Chen, Fangfang Shi, Chen Yang, Guangfeng Mao, Chunguang Zhou, Limin Liu, Xi Yang, Yueming Song
{"title":"Lentivirus-shRNA Mediated Prolyl Hydroxylase 2 Knockdown Increases HIF-1α and Inhibits Nucleus Pulposus Cells Degeneration.","authors":"Qi Chen,&nbsp;Fangfang Shi,&nbsp;Chen Yang,&nbsp;Guangfeng Mao,&nbsp;Chunguang Zhou,&nbsp;Limin Liu,&nbsp;Xi Yang,&nbsp;Yueming Song","doi":"10.1159/000520795","DOIUrl":"https://doi.org/10.1159/000520795","url":null,"abstract":"<p><p>Hypoxia-inducible factor (HIF) plays a crucial role in regulating the hypoxia-inducible state of nucleus pulposus cells in the intervertebral disc. In addition, the oxygen-dependent conversion of HIF-1α in nucleus pulposus cells is controlled by the protein proline 4-hydroxylase domain (PHD) family. To explore whether HIF-1α can be regulated by modulating PHD homologs to inhibit nucleus pulposus degeneration, PHD2-shRNAs were designed and a PHD2 interference vector was constructed. The expression of HIF-1α and PHD2 genes in the nucleus pulposus cells in the experimental group was detected by RT-PCR, and the expression of HIF-1α, MMP-2, Aggrecan, and Col II proteins in the P0-P3 cells in the experimental group and the control group was detected by Western blotting. The apoptosis of P0-P3 nucleus pulposus cells was detected by flow cytometry. After lentivirus infection, the interference efficiency of the PHD2 gene decreased with cell passage. The apoptosis of P1-P3 cells in the experimental group was significantly lower than that in the control group or degeneration group. Compared to the control group, the expression of HIF-1α, Aggrecan, and Col II proteins increased significantly, and the expression of MMP-2 protein decreased significantly. In conclusion, interference with PHD2 can upregulate the expression of HIF-1α, accelerate anabolism, reduce catabolism, inhibit apoptosis of nucleus pulposus cells, and then these can inhibit degeneration of nucleus pulposus cells. Our results can provide an effective therapeutic target in intervertebral discs during intervertebral disc degeneration, and this may have important clinical significance.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9700299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Adoptive Immunotherapy: A Human Pluripotent Stem Cell Perspective. 过继免疫疗法:人类多能干细胞的观点。
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 Epub Date: 2023-01-04 DOI: 10.1159/000528838
Gyuhyung Jin, Yun Chang, Jackson Duke Harris, Xiaoping Bao
{"title":"Adoptive Immunotherapy: A Human Pluripotent Stem Cell Perspective.","authors":"Gyuhyung Jin, Yun Chang, Jackson Duke Harris, Xiaoping Bao","doi":"10.1159/000528838","DOIUrl":"10.1159/000528838","url":null,"abstract":"<p><p>The past decade has witnessed significant advances in cancer immunotherapy, particularly through the adoptive transfer of engineered T cells in treating advanced leukemias and lymphomas. Despite these excitements, challenges remain with scale, cost, and ensuring quality control of engineered immune cells, including chimeric antigen receptor T, natural killer cells, and macrophages. The advent of human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, has transformed immunotherapy by providing a scalable, off-the-shelf source of any desired immune cells for basic research, translational studies, and clinical interventions. The tractability of hPSCs for gene editing could also generate homogenous, universal cellular products with custom functionality for individual or combinatory therapeutic applications. This review will explore various immune cell types whose directed differentiation from hPSCs has been achieved and recently adapted for translational immunotherapy and feature forward-looking bioengineering techniques shaping the future of the stem cell field.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10318121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10125342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Developmental Characteristics of the Glomerular and Tubular Portion of the Nephron in the Human Foetal Kidney Cortex: Morphometrical and Immunohistochemical Analysis. 人胎儿肾皮质肾单位肾小球和肾小管部分的发育特征:形态计量学和免疫组织化学分析。
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 DOI: 10.1159/000525185
Milorad Antic, Marija Dakovic Bjelakovic, Aleksandar Petrovic, Marko Bjelakovic, Goran Radenkovic, Nikola Zivkovic, Miljan Krstic, Vladimir Antic
{"title":"Developmental Characteristics of the Glomerular and Tubular Portion of the Nephron in the Human Foetal Kidney Cortex: Morphometrical and Immunohistochemical Analysis.","authors":"Milorad Antic,&nbsp;Marija Dakovic Bjelakovic,&nbsp;Aleksandar Petrovic,&nbsp;Marko Bjelakovic,&nbsp;Goran Radenkovic,&nbsp;Nikola Zivkovic,&nbsp;Miljan Krstic,&nbsp;Vladimir Antic","doi":"10.1159/000525185","DOIUrl":"https://doi.org/10.1159/000525185","url":null,"abstract":"<p><p>This study aimed to morphometrically examine the development of glomeruli and tubules in the kidney cortex of human foetuses at different gestational ages (GAs). We also investigated the expression of the proliferation marker Ki-67 and apoptosis-related markers Bcl-2 and Bax during nephrogenesis using immunohistochemistry. Kidney samples from 38 human foetuses of both sexes with GA ranging from 13 to 40 weeks were analysed. The samples were divided into 7 groups based on GA, each corresponding to 1 lunar month. Foetal kidneys showed a spatiotemporal gradient of nephron differentiation with the transient stages of nephron anlage located in the nephrogenic zone and immature nephrons located in the subjacent maturation zone. In the inner cortex, nephrons establish the morphological characteristics of definitive nephrons. The average area, perimeter, and Feret's diameter of the glomeruli formed within the kidney cortex gradually decreased up to a period of 29-32 weeks of gestation and subsequently increased until a period of 37-40 weeks. There was a weak negative correlation with GA. In contrast, the areal density of glomeruli increased up to a period of 21-24 weeks and then gradually decreased until a period of 37-40 weeks, showing a moderate negative correlation with GA. The average area of renal tubules slightly decreased until a period of 21-24 weeks of gestation and then gradually increased until a period of 36-40 weeks, showing a moderate positive correlation with GA. The average areal density of renal tubules increased significantly until a period of 21-24 weeks of gestation, remained relatively constant until a period of 33-36 weeks, and then increased significantly at 36-40 weeks. There was a strong positive correlation with GA. Our results showed that Ki-67 was expressed in numerous cells of the metanephric mesenchyme, pretubular aggregates, renal vesicles, comma-shaped bodies, and early S-shaped bodies. During subsequent development and the spatial expansion of nephrons towards the mature zone, the expression of Ki-67 was markedly reduced. Similarly, Bcl-2 was strongly expressed in induced nephrogenic progenitor cells, pretubular aggregates, renal vesicles, and comma-shaped bodies. As vascularisation and maturation of the nephron proceeded, Bcl-2 staining became less intense and limited to the parietal layer of the Bowman's capsule and renal tubules. Weak Bax expression was observed in individual scattered cells within segments of the nephrons at all developmental stages. In the mature zone, more intense Bax staining was observed in the renal tubules.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9965061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Effects of Pulsatility on Arterial Endothelial and Smooth Muscle Cells. 脉动对动脉内皮细胞和平滑肌细胞的影响
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 Epub Date: 2022-03-28 DOI: 10.1159/000524317
Moustafa Meki, Ayman El-Baz, Palaniappan Sethu, Guruprasad Giridharan
{"title":"Effects of Pulsatility on Arterial Endothelial and Smooth Muscle Cells.","authors":"Moustafa Meki, Ayman El-Baz, Palaniappan Sethu, Guruprasad Giridharan","doi":"10.1159/000524317","DOIUrl":"10.1159/000524317","url":null,"abstract":"<p><p>Continuous flow ventricular assist device (CFVAD) support in advanced heart failure patients causes diminished pulsatility, which has been associated with adverse events including gastrointestinal bleeding, end organ failure, and arteriovenous malformation. Recently, pulsatility augmentation by pump speed modulation has been proposed as a means to minimize adverse events. Pulsatility primarily affects endothelial and smooth muscle cells in the vasculature. To study the effects of pulsatility and pulse modulation using CFVADs, we have developed a microfluidic co-culture model with human aortic endothelial (ECs) and smooth muscle cells (SMCs) that can replicate physiologic pressures, flows, shear stresses, and cyclical stretch. The effects of pulsatility and pulse frequency on ECs and SMCs were evaluated during (1) normal pulsatile flow (120/80 mmHg, 60 bpm), (2) diminished pulsatility (98/92 mmHg, 60 bpm), and (3) low cyclical frequency (115/80 mmHg, 30 bpm). Shear stresses were estimated using computational fluid dynamics (CFD) simulations. While average shear stresses (4.2 dynes/cm2) and flows (10.1 mL/min) were similar, the peak shear stresses for normal pulsatile flow (16.9 dynes/cm2) and low cyclic frequency (19.5 dynes/cm2) were higher compared to diminished pulsatility (6.45 dynes/cm2). ECs and SMCs demonstrated significantly lower cell size with diminished pulsatility compared to normal pulsatile flow. Low cyclical frequency resulted in normalization of EC cell size but not SMCs. SMCs size was higher with low frequency condition compared to diminished pulsatility but did not normalize to normal pulsatility condition. These results may suggest that pressure amplitude augmentation may have a greater effect in normalizing ECs, while both pressure amplitude and frequency may be required to normalize SMCs morphology. The co-culture model may be an ideal platform to study flow modulation strategies.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10782761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9596333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
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