Journal of immunology and regenerative medicine最新文献

{"title":"The effect of normal, metaplastic, and neoplastic esophageal extracellular matrix upon macrophage activation","authors":"Lindsey T. Saldin ,&nbsp;Molly Klimak ,&nbsp;Ryan C. Hill ,&nbsp;Madeline C. Cramer ,&nbsp;Luai Huleihel ,&nbsp;Xue Li ,&nbsp;Maria Quidgley-Martin ,&nbsp;David Cardenas ,&nbsp;Timothy J. Keane ,&nbsp;Ricardo Londono ,&nbsp;George Hussey ,&nbsp;Lori Kelly ,&nbsp;Juliann E. Kosovec ,&nbsp;Emily J. Lloyd ,&nbsp;Ashten N. Omstead ,&nbsp;Li Zhang ,&nbsp;Alejandro Nieponice ,&nbsp;Blair Jobe ,&nbsp;Kirk Hansen ,&nbsp;Ali H. Zaidi ,&nbsp;Stephen F. Badylak","doi":"10.1016/j.regen.2020.100037","DOIUrl":"10.1016/j.regen.2020.100037","url":null,"abstract":"<div><h3>Introduction</h3><p><span><span>Macrophages are capable of extreme plasticity and their activation state has been strongly associated with solid tumor<span> growth progression and regression. Although the macrophage response<span> to extracellular matrix (ECM) isolated from normal tissue is reasonably well understood, there is a relative dearth of information regarding their response to ECM isolated from chronically inflamed tissues, pre-neoplastic tissues, and neoplastic tissues. </span></span></span>Esophageal adenocarcinoma<span> (EAC) is a type of neoplasia driven by chronic inflammation in the distal esophagus, and the length of the esophagus provides the opportunity to investigate macrophage behavior in the presence of ECM isolated from a range of disease states within the same organ. </span></span><strong>Methods.</strong><span><span> Normal, metaplastic, and neoplastic ECM hydrogels were prepared from decellularized EAC tissue. The hydrogels were evaluated for their nanofibrous structure (SEM), biochemical profile (targeted and global proteomics), and direct effect upon macrophage (THP-1 cell) activation state (qPCR, </span>ELISA, immunolabeling) and indirect effect upon epithelial cell (Het-1A) migration (Boyden chamber). </span><strong>Results.</strong><span><span> Nanofibrous ECM hydrogels from the three tissue types<span> could be formed, and normal and neoplastic ECM showed distinctive protein profiles by targeted and global mass spectroscopy. ECM proteins functionally related to cancer and tumorigenesis were identified in the neoplastic esophageal ECM including collagen alpha-1(VIII) chain (COL8A1), lumican<span><span>, and elastin. Metaplastic and neoplastic esophageal ECM induce distinctive effects upon THP-1 macrophage signaling compared to normal esophageal ECM. These effects include activation of pro-inflammatory IFNγ and TNFα gene expression and anti-inflammatory IL1RN gene expression. Most notably, neoplastic ECM robustly increased macrophage TNFα </span>protein expression. The </span></span></span>secretome<span> of macrophages pre-treated with metaplastic and neoplastic ECM increases the migration of normal esophageal epithelial cells, similar behavior to that shown by tumor cells. Metaplastic ECM shows similar but less pronounced effects than neoplastic ECM suggesting the abnormal signals also exist within the pre-cancerous state. </span></span><strong>Conclusion.</strong> A progressively diseased ECM, as exists within the esophagus exposed to chronic gastric reflux, can provide insights into novel biomarkers of early disease and identify potential therapeutic targets.</p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"13 ","pages":"Article 100037"},"PeriodicalIF":0.0,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regen.2020.100037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38941909","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":"Tissue engineering of the lymphoid organs","authors":"Caleb Harff ,&nbsp;Angela Panoskaltsis-Mortari","doi":"10.1016/j.regen.2021.100049","DOIUrl":"10.1016/j.regen.2021.100049","url":null,"abstract":"<div><p><span><span><span>The lymphoid system<span> protects the body from pathogens through organs that produce </span></span>immune cells<span><span> and facilitate immune surveillance. The study and </span>treatment of a variety of pathologies affecting or interacting with the immune system can benefit from </span></span>tissue engineering strategies. These designs can be implemented </span><em>in vitro</em> and <em>in vivo</em><span><span><span> through a variety of fabrication methods. Here we describe structure, cell types, and signaling found in the bone marrow niche, </span>thymus<span>, peripheral lymphoid organs, and lymphatic </span></span>vasculature<span>. We then summarize lymphoid tissue engineering studies from recent reports, and choice of design components including scaffolds, stromal cells, and chemical or physical signals. Finally, we discuss the current limitations and future of this field.</span></span></p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"13 ","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regen.2021.100049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87601227","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":"Healing activities of Cramoll and xyloglucan membrane in cutaneous wounds of diabetic mice","authors":"Fernanda M. de Andrade ,&nbsp;Fernanda P.A. Neves ,&nbsp;Priscilla B.S. de Albuquerque ,&nbsp;Adelmo C. Aragão-Neto ,&nbsp;Jannyson J.B. Jandú ,&nbsp;Luana C.B.B. Coelho ,&nbsp;Maria H.M. Lima-Ribeiro ,&nbsp;Álvaro A.C. Teixeira ,&nbsp;Maria G. Carneiro-da-Cunha ,&nbsp;Valéria W. Teixeira ,&nbsp;Maria T.S. Correia","doi":"10.1016/j.regen.2021.100045","DOIUrl":"10.1016/j.regen.2021.100045","url":null,"abstract":"<div><p>This study evaluated the healing potential of free Cramoll, a xyloglucan membrane extracted from <em>Hymenaea courbaril</em><span><span> (HcXM) and Cramoll immobilized in HcXM (Cramoll-HcXM), in cutaneous wounds of diabetic mice<span><span> induced by alloxan. Sixty male </span>Swiss albino mice<span><span><span> were randomly divided into four experimental groups (15 animals): Control; Cramoll; HcXM; and Cramoll-HcXM. Wounds, on the animals’ back after anesthesia and trichotomy, were treated daily, and clinical analysis was performed daily. Microbiological, wound retraction, histological and collagen I and III quantification analyses were performed on the 2nd, 7th and 12th days of treatment. During the 12 days of treatment no contamination was observed to any </span>experimental wounds<span>. Reepithelialization was accelerated in Cramoll, HcXM and Cramoll-HcXM groups and wound retraction was statistically superior in the Cramoll group. The Cramoll and HcXM groups, after 12 days of treatment, presented epidermis and </span></span>dermis with typical characteristics of healthy skin, with greater deposition of </span></span></span>type 1 collagen<span>. The treatment of cutaneous wounds in diabetic mice with Cramoll and HcXM accelerates the healing process when used individually, however, inflammatory infiltrate<span> and fibrovascular tissue persisted in the Cramoll-HcXM group. According to the results, this is the first report on the use of a lectin as a healer in induced diabetic mice; Cramoll and HcXM are excellent compounds for repairing skin wounds in diabetics.</span></span></span></p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"13 ","pages":"Article 100045"},"PeriodicalIF":0.0,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regen.2021.100045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81098796","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":"Progress in the production of haematopoietic stem and progenitor cells from human pluripotent stem cells","authors":"Antonella Fidanza,&nbsp;Lesley M. Forrester","doi":"10.1016/j.regen.2021.100050","DOIUrl":"10.1016/j.regen.2021.100050","url":null,"abstract":"<div><p>Cell therapies are currently used to treat many haematological diseases. These treatments range from the long-term reconstitution of the entire haematopoietic system using the most potent haematopoietic stem cells (HSCs) to the short-term rescue with mature functional end cells such as oxygen-carrying red blood cells and cells of the immune system that can fight infection and repair tissue. Limitations in supply and the risk of transmitting infection has prompted the design of protocols to produce some of these cell types from human pluripotent stem cells (hPSCs). Although it has proven challenging to generate the most potent HSCs directly from hPSCs, significant progress has been made in the development of differentiation protocols that can successfully produce haematopoietic progenitor cells and most of the mature cell lineages. We review the key steps used in the production of haematopoietic stem and progenitor cells (HSPCs) from hPSCs and the cell surface markers and reporter strategies that have been used to define specific transitions. Most studies have relied on the use of known markers that define HSPC production <em>in vivo</em> but more recently single cell RNA sequencing has allowed a less biased approach to their characterisation. Transcriptional profiling has identified new markers for naïve and committed hPSC-derived HSPC populations and trajectory analyses has provided novel insights into their lineage potential. Direct comparison of <em>in vitro-</em> and <em>in vivo</em>-derived RNA single cell sequencing datasets has highlights similarities and differences between the two systems and this deeper understanding will be key to the design and the tracking of improved and more efficient differentiation protocols.</p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"13 ","pages":"Article 100050"},"PeriodicalIF":0.0,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regen.2021.100050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39323180","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":"The immune response to the SLActive titanium dental implant surface in vitro is predominantly driven by innate immune cells","authors":"Florian Billing ,&nbsp;Meike Jakobi ,&nbsp;Dagmar Martin ,&nbsp;Karin Gerlach ,&nbsp;Elsa Arefaine ,&nbsp;Martin Weiss ,&nbsp;Nicole Schneiderhan-Marra ,&nbsp;Hanna Hartmann ,&nbsp;Christopher Shipp","doi":"10.1016/j.regen.2021.100047","DOIUrl":"10.1016/j.regen.2021.100047","url":null,"abstract":"<div><p>Biomaterial characteristics such as topography and wettability have been shown to influence the immune response to implanted medical devices. Thus, appropriate surface design considering the immune system has moved more into focus. Previous in vitro studies have commonly employed simplistic immune models and as such, the role of different immune cell populations, particularly those of the adaptive immune system, is still poorly understood. Here, we employed a biologically complex human-based in vitro model consisting of peripheral blood mononuclear cells (PBMC) to examine interactions between cells of the innate and adaptive immune system in the context of clinically used implants. To achieve this, five differently treated titanium surfaces were characterised in terms of physicochemical properties using contact angle measurement, XPS and confocal scanning microscopy. Cytokine analysis revealed different material surface properties to result in different immune responses with SLActive surface showing low levels of IL-6 and IL-8 but high levels of MCP-1. Cytokine and surface marker analysis in isolated populations of monocytes and lymphocytes and defined ratios revealed lymphocytes alone to be unaffected by the SLActive biomaterial and except for a slight effect on HLA-DR expression indicated no activation of monocytes by lymphoid cells. On lymphocytes, CD16 and HLA-DR expression was unaffected by monocytes under physiological conditions but was elevated with high levels of monocytes present. Intracellular cytokine staining in whole PBMC cultures confirmed monocytes to be responsible for the observed immune response, with minimal involvement of lymphocytes. Expression of the pro-inflammatory cytokines IL-8 and TNF-α in monocytes peaked 12 h after biomaterial contact, while the expression of surface markers HLA-DR and CD86 continued to rise 72 h following contact. These results collectively suggest the immune response to titanium biomaterials in the first 72 h in vitro to be almost exclusively driven by the innate rather than the adaptive immune system.</p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"13 ","pages":"Article 100047"},"PeriodicalIF":0.0,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regen.2021.100047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81421839","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":"Improvements in stem cell to beta-cell differentiation for the treatment of diabetes","authors":"Nicole A.J. Krentz","doi":"10.1016/j.regen.2021.100043","DOIUrl":"10.1016/j.regen.2021.100043","url":null,"abstract":"<div><p><span>Since the generation of human embryonic and induced pluripotent stem cells<span><span>, regenerative cell-based approaches for the treatment of diabetes have gained popularity. One strategy is to generate an unlimited source of insulin-producing pancreatic β-cells from human </span>pluripotent stem cells<span><span>. As such, major effort continues to be placed in creating efficient differentiation protocols that generate functional β-like cells from human pluripotent stem cells. In this review, I provide the historical context of stem cell differentiation protocols towards the aim of generating functional β-like cells. I also highlight recent advancements in differentiation protocols, including enrichment of cell populations using </span>cell surface markers<span>, suspension culture to mimic </span></span></span></span><em>in vivo</em><span> development, and the importance of hippo signalling<span> in endocrine cell fate. I conclude by suggesting future endeavors that have the potential to further improve differentiation protocols to achieve the ultimate goal of a cell-replacement therapy for diabetes.</span></span></p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"12 ","pages":"Article 100043"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regen.2021.100043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90053730","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":"Induced pluripotent stem cell-derived, genetically engineered myeloid cells as unlimited cell source for dendritic cell-related cancer immunotherapy","authors":"Rong Zhang ,&nbsp;Tianyi Liu ,&nbsp;Nobuhiro Tsuchiya ,&nbsp;Hiroaki Mashima ,&nbsp;Tsuyoshi Kobayashi ,&nbsp;Tetsuya Nakatsura ,&nbsp;Hideki Ohdan ,&nbsp;Itaru Endo ,&nbsp;Satoru Senju ,&nbsp;Yasushi Uemura","doi":"10.1016/j.regen.2021.100042","DOIUrl":"10.1016/j.regen.2021.100042","url":null,"abstract":"<div><p><span><span><span><span><span>Cancer immunotherapy is a unique </span>treatment modality that uses the body's immune system to eliminate </span>cancer cells<span>. Immune checkpoint blockades, which inhibit </span></span>immunosuppressive<span> mechanisms to enhance cancer-reactive T-cell responses, have expanded cancer-treatment options because they can induce the regression of cancer that is refractory to existing treatments. However, many patients do not respond to immune checkpoint blockades, and new therapies are needed to overcome resistance to treatment. In recent years, researchers have begun developing methods to generate immune cells, which play an important role in eliminating cancer, from </span></span>induced pluripotent stem cells (iPSCs) and have been administered to humans in </span>clinical trials<span><span>. This therapy can potentially replace existing cell-based cancer immunotherapies as the next generation of hybrid-cell therapies that combine immune cell therapy, regenerative medicine, and gene therapy. Previously, we constructed cytokine-dependent proliferating </span>myeloid cells (induced pluripotent stem cell-derived proliferating myeloid cells; iPSC-pMCs) by inducing myeloid cell differentiation from iPSCs and subsequently introducing proliferation factors. Once constructed, the cells have proliferative potential, which eliminates the need for re-differentiating myeloid cells from iPSCs, resulting in an indefinite and stable supply of homogeneous cells with little investment of cost and effort. In this review, we discuss the potential of iPSC-pMC-based immune cell products as immune-stimulating agents for cancer that are refractory to checkpoint blockade.</span></p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"12 ","pages":"Article 100042"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regen.2021.100042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81473799","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":"Mitigating the foreign body response through ‘immune-instructive’ biomaterials","authors":"Lisa Kämmerling ,&nbsp;Leanne E. Fisher ,&nbsp;Ezgi Antmen ,&nbsp;Gorkem M. Simsek ,&nbsp;Hassan M. Rostam ,&nbsp;Nihal E. Vrana ,&nbsp;Amir M. Ghaemmaghami","doi":"10.1016/j.regen.2021.100040","DOIUrl":"10.1016/j.regen.2021.100040","url":null,"abstract":"<div><h3>Objectives</h3><p><span>Biomaterials are routinely used in clinical applications. A key to the clinical success of implanted biomaterials is not eliciting detrimental immune responses. In this article, we provide an overview of immune responses to biomaterials, along with biomaterial-based approaches to mitigate the adverse host reactions while supporting pro-healing immune responses. We also review existing </span><em>in-vitro</em><span> models used to assess the biocompatibility of biomaterials.</span></p></div><div><h3>Key findings</h3><p>Once implanted, biomaterials are often detected as foreign bodies by the immune system, triggering detrimental immune responses. Such responses could damage host tissues and impair the function of implanted materials or devices. Therefore, there is substantial interest in developing new materials and tools with the ability to modulate immune responses to support tissue regeneration<span> and healing processes. However, the bioengineering of immune responses through biomaterials requires detailed understanding of how the immune system typically responds to foreign materials. This knowledge can inform designing materials with bio-instructive chemistries and/or surface attributes. In this review, first we briefly discuss basic aspects of the foreign body response followed by different strategies for developing ‘immune-instructive’ biomaterials, models to test their efficacy and examples of their clinical applications.</span></p></div><div><h3>Conclusions</h3><p>Promising progress has been made in the field of biomaterial engineering however, how different immune cells<span> interact with biomaterials is yet to be fully elucidated. A better understanding of cell-material interactions, and particularly the impact of inter-individual variations, will allow the development of new generation of more personalised ‘immune-instructive’ biomaterials and medical devices to modulate immune responses towards anti-inflammatory and pro-healing phenotypes.</span></p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"12 ","pages":"Article 100040"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regen.2021.100040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91242115","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 matrix scaffolds derived from different musculoskeletal tissues drive distinct macrophage phenotypes and direct tissue-specific cellular differentiation","authors":"Olwyn R. Mahon ,&nbsp;David C. Browe ,&nbsp;Pedro J. Diaz-Payno ,&nbsp;Pierluca Pitacco ,&nbsp;Kyle T. Cunningham ,&nbsp;Kingston H.G. Mills ,&nbsp;Aisling Dunne ,&nbsp;Daniel J. Kelly","doi":"10.1016/j.regen.2021.100041","DOIUrl":"10.1016/j.regen.2021.100041","url":null,"abstract":"<div><p>The host immune response, specifically macrophage function, is a critical determinant of biomaterial success or failure post-implantation. Extracellular matrix (ECM) derived scaffolds have been shown to promote a pro-regenerative macrophage phenotype and a more constructive remodelling outcome. Here we demonstrate that macrophages adopt distinct phenotypes when exposed to articular cartilage (AC), ligament (LIG) and growth plate (GP) derived ECM scaffolds. Macrophages were generally unresponsive to LIG-derived ECM, adopted an M2-like phenotype when exposed to AC-derived ECM, and a hybrid M1-M2 phenotype when exposed to GP-ECM. Furthermore, macrophages expressed higher levels of pro-chondrogenic factors, such as FGF2, when exposed to AC-ECM, and higher levels of angiogenic and pro-osteogenic factors, such as VEGF, IL-6 and TNF, when exposed to GP-ECM. In addition, we observed that they can differentially direct the differentiation of skeletal stem cells, whereby AC-ECM promotes the chondrogenic differentiation and GP-ECM the osteogenic differentiation of multipotent stem/stromal cells (MSCs). <em>In vivo</em> characterisation of immune cell subsets following scaffold implantation into a large bone defect demonstrated that AC-ECM drives an M2 macrophage phenotype, while GP-ECM containing scaffolds promoted a hybrid M1-M2 phenotype and enhanced vascularisation and vessel maturation. This distinct response to the implantation of GP-ECM containing scaffolds was associated with increased CD45⁺ leukocyte and CD3⁺ T cell infiltration, accompanied by elevated concentrations of IFN-γ and IL-17. Taken together this work demonstrates that the source tissue of ECM scaffolds plays a key role in regulating the phenotype of both macrophages and skeletal stem cells. Furthermore, these ECMs can direct the cellular differentiation and production of growth factors essential for the regeneration of their source tissue. This work highlights the need for a more thorough characterisation of innate immune cell subsets post-biomaterial implantation.</p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"12 ","pages":"Article 100041"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regen.2021.100041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83434851","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":"Osteogenic differentiation driven by osteoclasts and macrophages","authors":"Talita Stessuk ,&nbsp;Johanna Husch ,&nbsp;Inge AT. Hermens ,&nbsp;Sandra Hofmann ,&nbsp;Jeroen JJP. van den Beucken","doi":"10.1016/j.regen.2021.100044","DOIUrl":"10.1016/j.regen.2021.100044","url":null,"abstract":"<div><h3>Introduction</h3><p>Osteoclasts are bone-resorbing cells closely related to bone turnover, whereas different macrophage subtypes contribute to bone fracture healing. As osteoclasts and macrophages share the same hematopoietic origin, the difference between both cell types on osteoblast coupling, crosstalk extent and consequent bone formation remains poorly understood. This study compares the potential of primary cells that are routinely considered as osteoclast and macrophage cultures on their ability to support osteogenic differentiation of human mesenchymal stromal cells (hMSCs).</p></div><div><h3>Methods</h3><p>Human Peripheral Blood Mononuclear Cells (hPBMCs) were used to obtain macrophage or osteoclast cultures using appropriate stimulatory factors. With different seeding densities of hPBMCs, conditioned media from macrophage or osteoclast cultures were harvested for comparative evaluation of effects thereof on the osteogenic differentiation of hMSCs. Specific cytological staining was used to qualitatively evaluate macrophage and osteoclast cultures. Additionally, quantitative data on hMSC proliferation, osteogenic differentiation and mineralization were obtained via biochemical assays.</p></div><div><h3>Results</h3><p>Conditioned medium from osteoclast cultures obtained via low hPBMCs seeding densities, but not from high hPBMCs seeding densities or macrophages, stimulated hMSC osteogenic differentiation and mineralization. Upon cellular crosstalk, both pre-differentiated osteoclasts and non-polarized macrophages equally supported early hMSC osteogenic differentiation and mineralization, as confirmed by increased alkaline phosphatase levels within 7 days and increased calcium content within 14 days in comparison with undifferentiated controls. Initial hPBMCs seeding density strongly influences osteoclastogenesis and the paracrine effect of the resultant osteoclast population on the osteogenic differentiation of hMSCs. In addition, only in indirect coculture, macrophages provide similar stimulatory effects as pre-differentiated osteoclasts on the osteogenic differentiation of MSCs and mineralization.</p></div><div><h3>Conclusion</h3><p>Our results demonstrate stimulatory effects of osteoclast conditioned medium on hMSC osteogenic differentiation, depending on initial hPBMC seeding density. In addition, we show that osteoclast and macrophage cultures contain pools of polarized macrophages, which may be involved in the osteogenic effects. Our data provide insight into bone tissue engineering approaches by using multicellular interactions related to bone remodeling and healing for the in vitro modulation of osteogenic differentiation.</p></div>","PeriodicalId":94333,"journal":{"name":"Journal of immunology and regenerative medicine","volume":"12 ","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regen.2021.100044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84004313","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}