Journal of immunology and regenerative medicine最新文献

{"title":"Elevated oxidative phosphorylation is critical for immune cell activation by polyethylene wear particles","authors":"Chima V. Maduka ,&nbsp;Maxwell M. Kuhnert ,&nbsp;Oluwatosin M. Habeeb ,&nbsp;Anthony Tundo ,&nbsp;Ashley V. Makela ,&nbsp;Stuart B. Goodman ,&nbsp;Christopher H. Contag","doi":"10.1016/j.regen.2022.100069","DOIUrl":"https://doi.org/10.1016/j.regen.2022.100069","url":null,"abstract":"<div><p>Chronic inflammation is a major concern after total joint replacements (TJRs), as it is associated with bone loss, limited bone-implant integration (osseointegration), implant loosening and failure. Inflammation around implants could be directed away from adverse outcomes and toward enhanced osseointegration and improved surgical outcome. Activated macrophages exposed to polyethylene particles play a dominant inflammatory role, and exhibit elevated mitochondrial oxidative phosphorylation (OXPHOS) whose role is unclear. By probing the contribution of the electron transport chain (ETC), we show that increased oxygen consumption does not contribute to bioenergetic (ATP) levels in fibroblasts and primary bone marrow-derived macrophages activated by polyethylene particles. Rather, it generates reactive oxygen species (ROS) at complex I by increasing mitochondrial membrane potential in macrophages. Inhibition of OXPHOS in a dose-dependent manner without affecting glycolysis was accomplished by targeting complex I of the ETC using either rotenone or metformin. Metformin decreased mitochondrial ROS and, subsequently, expression of proinflammatory cytokines, including IL-1β, IL-6 and MCP-1 but not TNF-α in macrophages. These results highlight the contribution of mitochondrial bioenergetics to activation of immune cells by polyethylene wear particles, offering new opportunities to modulate macrophage states toward desired clinical outcomes.</p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"19 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49871811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles present in bone, blood and extracellular matrix have distinctive characteristics and biologic roles","authors":"Madeline C. Cramer ,&nbsp;William A. D'Angelo ,&nbsp;Marley J. Dewey ,&nbsp;Allison M. Manuel ,&nbsp;Steven J. Mullett ,&nbsp;Stacy G. Wendell ,&nbsp;Dobrawa Napierala ,&nbsp;Peng Jiang ,&nbsp;Stephen F. Badylak","doi":"10.1016/j.regen.2022.100066","DOIUrl":"https://doi.org/10.1016/j.regen.2022.100066","url":null,"abstract":"<div><h3>Introduction</h3><p>Extracellular vesicles (EV) have long been recognized as an important means of cell to cell communication, but current metrics to delineate various subpopulations of EV are limited. Recently, a distinctive subpopulation of EV embedded within the extracellular matrix of soft tissues, termed matrix-bound nanovesicles (MBV), has been described. Although the lipid membrane composition and intravesicular cargo of MBV clearly differ from liquid phase EV (i.e. exosomes), a more comprehensive characterization of the physical and biologic properties of MBV vs. exosomes and those of a separate subpopulation of EV, specifically bone matrix vesicles, would contribute to our understanding of the biogenesis and physiologic role of these three EV subpopulations.</p></div><div><h3>Results</h3><p>The physical characteristics, protein and miRNA cargo profiling, vesicle membrane lipidomics, and immunomodulatory activity were used to compare skeletal muscle-derived MBV, liquid phase plasma exosomes, and mineralization-competent matrix vesicles of provisional bone matrix. We show that despite similar physical characteristics, these three preparations of EV represent distinct entities with different biologic activity.</p></div><div><h3>Conclusion</h3><p>These results inform metrics for the categorization of EV and provide tools for the isolation of EV for potential diagnostic and therapeutic applications.</p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"18 ","pages":"Article 100066"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468498822000087/pdfft?md5=5428d500883dc7f68f8347445f9bec5d&pid=1-s2.0-S2468498822000087-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72277708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles present in bone, blood and extracellular matrix have distinctive characteristics and biologic roles","authors":"Madeline C. Cramer, W. D’Angelo, Marley J. Dewey, Allison M. Manuel, S. Mullett, S. Wendell, D. Napierała, Peng Jiang, S. Badylak","doi":"10.1016/j.regen.2022.100066","DOIUrl":"https://doi.org/10.1016/j.regen.2022.100066","url":null,"abstract":"","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84883103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro inflammatory and immune response to uncrosslinked hyaluronic acid (HA) and HA fillers","authors":"Christopher K. Hee,&nbsp;Darin J. Messina","doi":"10.1016/j.regen.2022.100065","DOIUrl":"https://doi.org/10.1016/j.regen.2022.100065","url":null,"abstract":"<div><h3>Introduction</h3><p>Delayed-onset nodules are a complication associated with soft tissue filler products, including hyaluronic acid (HA) fillers; however, the etiology of these events remains unclear. The role of uncrosslinked HA and crosslinked HA fillers in the response of immune cells (dendritic cells, B cells, and T cells) was evaluated with and without concurrent bacterial stimulation.</p></div><div><h3>Methods</h3><p>Uncrosslinked HA of varying molecular weights and crosslinked HA fillers were tested in a series of in vitro assays to evaluate 1) human monocyte activation; 2) activation, maturation, and migration of human monocyte-derived dendritic cells (MoDC); 3) T-cell activation and associated skin damage; and 4) T-cell–mediated B-cell response. For the latter assay, the HA test articles were also evaluated following stimulation by bacteria.</p></div><div><h3>Results</h3><p>When treated with lipopolysaccharide (LPS) as a positive control, inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-10, IL-12p70, and tumor necrosis factor [TNF]-α) released by MoDC were significantly upregulated. Treatment of the MoDC with HA (0.776, 150, and 485 kDa) did not result in stimulation of IL-1β, IL-6, IL-10, and IL-12p70, although increased TNF-α was observed with all HA test samples. The TNF-α increase was significantly lower for HA samples (1.5–2.64 pg/mL) compared with LPS (966.96–4834.18 pg/mL). Similarly, treatment of MoDC with HA samples did not result in expression of surface markers indicative of dendritic cell maturation. MoDC treated with 0.776 and 150 kDa HA, but not with 485 kDa HA, had significantly increased migration toward fetal bovine serum, but not C–C motif chemokine ligand 21 (CCL21). In the T-cell activation and skin damage assay, VYC-15L, degraded VYC-15L, HYC-24L+, and oligosacharride HA samples were negative in the T-cell proliferation and interferon-γ assays at all tested concentrations. The degraded HYC-24L + sample was borderline at the highest concentration and negative at the middle and low concentrations. Skin damage was determined to be negative for all HA samples at all concentrations. In the human monocyte activation assay, all tested uncrosslinked HA samples (5, 150, and 731 kDa) were determined to be non-sensitizing (i.e., did not activate monocyte cells). In the T-cell–mediated B-cell activation assay, treatment with HA oligosaccharides, uncrosslinked HA, and crosslinked HA fillers did not result in any consistent stimulation of any cytokines measured. A molecular weight–dependent decrease in the secreted immunoglobulin G (IgG) was observed, and this effect was more pronounced with the crosslinked HA fillers. Addition of heat-inactivated <em>Cutibacterium acnes</em> bacteria (HIB) to uncrosslinked HA and crosslinked HA fillers resulted in increased cytokine production similar to when HIB was tested alone. The decrease in secreted IgG observed for crosslinked HA filler samples without HIB was maintained with","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"17 ","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468498822000075/pdfft?md5=e5a041607ef06fc4ebe00d93f36a143b&pid=1-s2.0-S2468498822000075-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137439255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opportunities and impediments of human pluripotent stem cell-derived islets in the treatment of diabetes","authors":"Nidheesh Dadheech ,&nbsp;Nerea Cuesta-Gomez ,&nbsp;Ila Tewari Jasra ,&nbsp;Kevin Verhoeff ,&nbsp;Braulio Marfil Garza ,&nbsp;Omar Mouhammed ,&nbsp;A.M. James Shapiro","doi":"10.1016/j.regen.2022.100064","DOIUrl":"10.1016/j.regen.2022.100064","url":null,"abstract":"<div><p><span><span>Progress in human pluripotent stem cells has opened up an opportunity to autologous β-cell replacement therapies </span>in patients<span><span> with diabetes. Such an approach could render immunologically compatible islets from an unconstrained source without requirement for chronic immune suppression. Several proof-of-concept studies have generated stem cell-derived islets (SC-islets) capable of reversing diabetes in rodents and with similar functional characteristics to human donor islets. Autologous SC-islets offer potential to improve the life of patients living with diabetes by enabling cell replacement therapy that provides physiologic </span>glycemic control<span> with less risk to the recipient. Such efforts are impeded from ongoing challenges in scalability, latent potential for teratogenicity, an inability to fully recapitulate metabolic responses observed with primary islets, and protection from autoimmune recurrence in the setting of </span></span></span>Type 1 diabetes<span><span>. In this review, we outline potential opportunities and impediments for successful clinical translation of SC-islets as an effective therapy for patients with all forms of diabetes. We discuss recent advancements in scale-up manufacturing, the promise of gene-editing for optimized cellular protection, and methods to deliver safe and immune shielded cells to improve engraftment<span> and survival. Finally, we discuss in detail goals and challenges in islet bioengineering and emphasize the need for improved methods to overcome the roadblocks in </span></span>translating autologous SC-islet cell therapies to the clinic.</span></p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"17 ","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77851063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polarization of human iPSC-derived macrophages directs their immunological response to secondary pro-inflammatory stimuli","authors":"Maximilian Schinke ,&nbsp;Greta Meyer ,&nbsp;Anna Rafiei Hashtchin ,&nbsp;Miriam Hetzel ,&nbsp;Shifaa M. Abdin ,&nbsp;Tim Wegner ,&nbsp;Adrian Schwarzer ,&nbsp;Gesine Hansen ,&nbsp;Axel Schambach ,&nbsp;Nico Lachmann ,&nbsp;Mania Ackermann","doi":"10.1016/j.regen.2022.100061","DOIUrl":"10.1016/j.regen.2022.100061","url":null,"abstract":"<div><p><span><span><span>Macrophages can be found in various tissues and play an important role in organ function by sensing and eradicating pathogens, regulating immune responses and contributing to tissue </span>homeostasis and repair. Nowadays, increasing numbers of macrophage-based cell therapies are entering (pre-) clinical studies e.g. for the </span>treatment<span><span> of liver cirrhosis. Given limited availability of suitable donors as well as problems with variability in quantities and qualities of human </span>monocytes<span> that can be derived from apheresis<span>, induced pluripotent stem cells (iPSC) offer an attractive source of therapeutic macrophages. However, considering the diverse functions, activation stages and overall plasticity of macrophages, further knowledge about (i) the potential to induce different activation stages in iPSC-derived macrophages (iPSC-Mac) as well as (ii) the stability of these phenotypes upon additional external stimuli is of high relevance. We here demonstrate that iPSC-Mac produced in a scalable differentiation platform can be polarized into defined pro- (M1) and anti-inflammatory (M2) activation stages characterized by specific surface marker expression, </span></span></span></span>cytokine secretion<span><span><span> and whole transcriptome analysis, similarly to peripheral blood-derived macrophages. Even more importantly, we show that differentially polarized iPSC-Mac maintained key characteristics of their activation status upon a subsequent inflammatory trigger. </span>Interferon (IFN) γ polarized, M1-iPSC-Mac demonstrated an enhanced inflammatory response after additional </span>lipopolysaccharide (LPS) stimulation, whereas Interleukin (IL)-4 stimulated M2a iPSC-Mac and IL-10/TGFβ primed M2c iPSC-Mac showed a reduced activation upon LPS treatment and maintained expression of anti-inflammatory genes. Together, our data demonstrate that defined polarized iPSC-Mac subsets can be generated. Moreover, these cells maintain key characteristics of their activation profile upon a subsequent inflammatory trigger. Thus, the use of stably polarized iPSC-Mac has the potential to further improve the applicability and efficacy of macrophage-based therapies.</span></p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"17 ","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73640094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The type 1 diabetes immune niche: Immunomodulatory biomaterial design considerations for beta cell transplant therapies","authors":"Claire E. Hilburger ,&nbsp;Matthew J. Rosenwasser ,&nbsp;Derfogail Delcassian","doi":"10.1016/j.regen.2022.100063","DOIUrl":"10.1016/j.regen.2022.100063","url":null,"abstract":"<div><p><span><span><span>Islet transplantation is a promising therapy for a subset of people with </span>Type 1 diabetes (T1D). However, beta </span>cell transplant </span>clinical trials<span><span> have largely failed to maintain long-term normal glycemia<span> in transplant recipients. This is broadly due to immune rejection of the transplanted islets themselves or the devices in which these cells are encapsulated. As an autoimmune condition, the T1D host presents a uniquely challenging immunological niche for the transplant of additional beta cells. An understanding of the autoimmune environment is crucial for the development of successful beta cell transplant therapies. Here, we provide an overview of the immune cell pathways leading to autoimmune T1D, and the resulting immune niche. Next, we examine biomaterial platforms that can be used for </span></span>cell transplantation<span>, and describe those that seek to modulate the immune environment to mitigate immune rejection. These approaches include delivery of localized immune cues, co-transplantation with immunomodulatory cells, strategies to engineer islets ex-vivo, and antigen-specific immunomodulation to generate operational tolerance. Finally, we describe therapies which seek to prevent T1D progression which could be repurposed to support beta cell transplantation and future immunoengineering design considerations for successful islet transplantation therapies.</span></span></p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"17 ","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74306202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining the profile: Characterizing cytokines in tendon injury to improve clinical therapy","authors":"Ilene M. Ellis ,&nbsp;Lauren V. Schnabel ,&nbsp;Alix K. Berglund","doi":"10.1016/j.regen.2022.100059","DOIUrl":"10.1016/j.regen.2022.100059","url":null,"abstract":"<div><p>Cytokine manipulation has been widely used to bolster innate healing mechanisms in an array of modern therapeutics. While other anatomical locations have a more definitive analysis of cytokine data, the tendon presents unique challenges to detection that make a complete portrayal of cytokine involvement during injury unattainable thus far. Without this knowledge, the advancement of tendon healing modalities is limited. In this review, we discuss what is known of the cytokine profile within the injured tendinous environment and the unique obstacles facing cytokine detection in the tendon while proposing possible solutions to these challenges. IL-1β, TNF-α, and IL-6 in particular have been identified as key cytokines for initiating tendon healing, but their function and temporal expression are still not well understood. Methods used for cytokine evaluation in the tendon including cell culture, tissue biopsy, and microdialysis have their strengths and limitations, but new methods and approaches are needed to further this research. We conclude that future study design for cytokine detection in the injured tendon should meet set criteria to achieve definitive characterization of cytokine expression to guide future therapeutics.</p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"16 ","pages":"Article 100059"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932644/pdf/nihms-1787468.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9372346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Augmenting engraftment of beta cell replacement therapies for T1DM","authors":"Saloni Aggarwal ,&nbsp;Andrew R. Pepper ,&nbsp;Najwa Al Jahdhami","doi":"10.1016/j.regen.2021.100058","DOIUrl":"10.1016/j.regen.2021.100058","url":null,"abstract":"<div><h3>Objectives</h3><p><span><span><span>For nearly a century, the therapeutic use of exogenous insulin remains the gold standard treatment strategy for patients living with </span>Type 1 Diabetes Mellitus (T1DM). While lifesaving, insulin can fail to prevent the secondary vascular disease and complications inherited with T1DM diagnosis, and for some, this may increase their risk of life-threatening </span>hypoglycemic<span><span> unawareness. In recent decades transplantation has been demonstrated as the only means (a replacement gold standard therapy) to effectively restore physiologically relevant glycemic control. Moreover, significant advancements in clinical </span>islet transplantation<span> have yielded greater incidences of durable insulin-independence, rescindment of critical hypoglycemia and prevention of comorbidities. Yet, the requisite of life-long immunosuppression and scarcity of a universal and potent cell supply, in addition to the challenges faced with such therapy </span></span></span><em>in vivo</em>, restricts the broad-spectrum application of cell-based therapies.</p></div><div><h3>Key findings</h3><p>Herein, this review presents the history, current status and persisting challenges confronting cell-based replacement therapies for T1DM. Lastly, we examine modern and future research opportunities designed to enhance the efficacy of cellular transplantation, thereby offering a potential functional cure to all those affected by T1DM.</p></div><div><h3>Conclusions</h3><p>Given the rapid progress in β-cell replacement therapy, it is hopeful that through multidisciplinary innovations, first-in-human stem cell trials, innocuous immunosuppression and efficacious extrahepatic transplant sites, β-cell replacement therapies will become the cornerstone treatment for the millions worldwide afflicated with T1DM.</p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"16 ","pages":"Article 100058"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90568270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum regarding missing declaration of competing interest statements in previously published articles","authors":"","doi":"10.1016/j.regen.2022.100060","DOIUrl":"https://doi.org/10.1016/j.regen.2022.100060","url":null,"abstract":"","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"16 ","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468498822000026/pdfft?md5=3a9265b1debe132a4cb566d8ebc00e16&pid=1-s2.0-S2468498822000026-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137435821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}