Regenerative Therapy最新文献

{"title":"A novel role of CD73-IFNγ signalling axis in human mesenchymal stromal cell mediated inflammatory macrophage suppression","authors":"Shashank Chandanala,&nbsp;Govind Mohan,&nbsp;David-Luther Manukonda,&nbsp;Anujith Kumar,&nbsp;Jyothi Prasanna","doi":"10.1016/j.reth.2024.05.011","DOIUrl":"10.1016/j.reth.2024.05.011","url":null,"abstract":"<div><h3>Introduction</h3><p>Immunomodulation is the predominant mechanism via which Mesenchymal stromal cells (MSCs) mediate their therapeutic benefits. However, inconsistent success in numerous clinical trials warrants a better understating of the molecular mechanisms regulating their immunomodulatory properties. CD73, an ecto-5′-nucleotidase is abundantly expressed by MSCs, however its precise role in regulating their immunomodulatory properties is still elusive. The present study explored the role of CD73 in Interferon-gamma (IFNγ) sensing and in turn their ability to suppress “inflammatory” M1 macrophages.</p></div><div><h3>Materials and methods</h3><p>CD73 knockdown MSCs (CD73-KDN) were initially assessed for expression of immunoregulatory molecules and IFNγ sensing ability by analysing expression of IFNγ signalling downstream targets such as pSTAT-1, Interferon-Stimulated Genes (ISG) and Indoleamine 2,3-dioxygnease (IDO), a prototypic IFNγ-induced immunomodulator. Next CD73-KDN MSCs were co-cultured with inflammatory M1 macrophages and evaluated for their ability to suppress them. To delineate the contributory role of CD73 and IFNγ signalling downstream target IDO, they were overexpressed independently in CD73-KDN MSCs and re-evaluated for their ability to suppress M1 macrophages.</p></div><div><h3>Results</h3><p>CD73-KDN MSCs exhibited reduced expression of immunoregulatory molecules and were refractory to IFNγ signalling as indicated by attenuated expression of pSTAT-1, Interferon-Stimulated Genes (ISG) and Indoleamine 2,3-dioxygnease (IDO) upon IFNγ exposure. Since sensing of inflammation is critical for MSC mediated immunomodulation, CD73-KDN MSCs were functionally evaluated for their ability to immune-modulate “inflammatory” M1 macrophages wherein they failed to suppress M1 macrophages. Interestingly, ectopic expression of either CD73 or IFNγ signalling target IDO1 in CD73-KDN MSCs restored their ability to suppress M1 macrophages, establishing the importance of CD73-IFNγ signalling axis in MSC-mediated inflammatory macrophage suppression.</p></div><div><h3>Conclusion</h3><p>The present study uncovers the unexplored role of CD73-IFNγ axis in MSC-mediated M1 macrophage suppression. MSC-educated macrophages are the actual immune-modulators at MSC transplant sites, thus CD73 can serve as a key immune-potency marker for benchmarking therapeutically relevant MSCs.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 89-101"},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235232042400097X/pdfft?md5=6168362cb8fd0b6afca7b553284f90cb&pid=1-s2.0-S235232042400097X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141234501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring calcium-free alternatives in endochondral bone repair tested on In vivo trials - A review","authors":"William Cárdenas-Aguazaco,&nbsp;Adriana Lorena Lara-Bertrand,&nbsp;Leonardo Prieto-Abello,&nbsp;Nicolás Barreto-López,&nbsp;Bernardo Camacho,&nbsp;Ingrid Silva-Cote","doi":"10.1016/j.reth.2024.05.017","DOIUrl":"https://doi.org/10.1016/j.reth.2024.05.017","url":null,"abstract":"<div><p>Bone repair via endochondral ossification is a complex process for the critical size reparation of bone defects. Tissue engineering strategies are being developed as alternative treatments to autografts or allografts. Most approaches to bone regeneration involve the use of calcium composites. However, exploring calcium-free alternatives in endochondral bone repair has emerged as a promising way to contribute to bone healing. By analyzing researches from the last ten years, this review identifies the potential benefits of such alternatives compared to traditional calcium-based approaches. Understanding the impact of calcium-free alternatives on endochondral bone repair can have profound implications for orthopedic and regenerative medicine. This review evaluates the efficacy of calcium-free alternatives in endochondral bone repair through <em>in vivo</em> trials. The findings may guide future research to develop innovative strategies to improve endochondral bone repair without relying on calcium. Exploring alternative approaches may lead to the discovery of novel therapies that improve bone healing outcomes.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 145-160"},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001044/pdfft?md5=1cecf4fd8849e6344c21b2da6e07a11e&pid=1-s2.0-S2352320424001044-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141240887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of in vivo-like multicellular liver organoids by mimicking developmental processes: A review","authors":"Ayumu Okumura,&nbsp;Kenji Aoshima,&nbsp;Naoki Tanimizu","doi":"10.1016/j.reth.2024.05.020","DOIUrl":"https://doi.org/10.1016/j.reth.2024.05.020","url":null,"abstract":"<div><p>Liver is involved in metabolic reactions, ammonia detoxification, and immunity. Multicellular liver tissue cultures are more desirable for drug screening, disease modeling, and researching transplantation therapy, than hepatocytes monocultures. Hepatocytes monocultures are not stable for long. Further, hepatocyte-like cells induced from pluripotent stem cells and <em>in vivo</em> hepatocytes are functionally dissimilar. Organoid technology circumvents these issues by generating functional <em>ex vivo</em> liver tissue from intrinsic liver progenitor cells and extrinsic stem cells, including pluripotent stem cells. To function as <em>in vivo</em> liver tissue, the liver organoid cells must be arranged precisely in the 3-dimensional space, closely mimicking <em>in vivo</em> liver tissue. Moreover, for long term functioning, liver organoids must be appropriately vascularized and in contact with neighboring epithelial tissues (e.g., bile canaliculi and intrahepatic bile duct, or intrahepatic and extrahepatic bile ducts). Recent discoveries in liver developmental biology allows one to successfully induce liver component cells and generate organoids. Thus, here, in this review, we summarize the current state of knowledge on liver development with a focus on its application in generating different liver organoids. We also cover the future prospects in creating (functionally and structurally) <em>in vivo</em>-like liver organoids using the current knowledge on liver development.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 219-234"},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235232042400107X/pdfft?md5=70e5984d630283fd1a9ee2c94e40da43&pid=1-s2.0-S235232042400107X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141294770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the wound healing process through local injection of exosomes derived from blood serum: An in vitro and in vivo assessment","authors":"Mehdi Rasti ,&nbsp;Amir Hossein Parniaei ,&nbsp;Leila Dehghani ,&nbsp;Salar Nasr Esfahani ,&nbsp;Hossein Mirhendi ,&nbsp;Vida Yazdani ,&nbsp;Vajihe Azimian Zavareh","doi":"10.1016/j.reth.2024.06.004","DOIUrl":"https://doi.org/10.1016/j.reth.2024.06.004","url":null,"abstract":"<div><h3>Introduction</h3><p>The skin plays a crucial role as a protective barrier against external factors, but disruptions to its integrity can lead to wound formation and hinder the natural healing process. Scar formation and delayed wound healing present significant challenges in skin injury treatment. While alternative approaches such as skin substitutes and tissue engineering exist, they are often limited in accessibility and cost. Exosomes have emerged as a potential solution for wound healing due to their regenerative properties.</p></div><div><h3>Methods</h3><p>In this study, exosomes were isolated from human blood serum using a kit. The exosomes were characterized, and their effects on cell migration were assessed <em>in vitro</em>. Additionally, the wound healing capacity of exosomes was evaluated <em>in vivo</em> using a rat full-thickness wound model.</p></div><div><h3>Results</h3><p>Our <em>in vitro</em> findings revealed that exosomes significantly promoted cell migration. <em>In vivo</em> experiments demonstrated that the injection of exosomes at different areas of the wound accelerated the wound healing process, resulting in wound closure, collagen synthesis, vessel formation, and angiogenesis in the wound area. These results suggest that exosomes have a promising therapeutic potential for expediting wound healing and minimizing scar formation.</p></div><div><h3>Conclusions</h3><p>The findings of this study highlight the potential of exosomes as a novel approach for enhancing wound healing. Exosomes showed positive effects on both cell migration and wound closure in <em>in vitro</em> and <em>in vivo</em> studies, suggesting their potential use as a regenerative therapy for skin injuries. Further research is needed to fully understand the mechanisms underlying the beneficial effects of exosomes on wound healing and to optimize their application in clinical settings.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 281-289"},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001123/pdfft?md5=067684090080373533843008cae53cd7&pid=1-s2.0-S2352320424001123-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141423553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel cell therapy with ex vivo cultured peripheral blood mononuclear cells significantly impacts angiogenesis in the murine ischemic limb model","authors":"Satomi Furukawa ,&nbsp;Rie Hirano ,&nbsp;Ai Sugawara ,&nbsp;Satoshi Fujimura ,&nbsp;Rica Tanaka","doi":"10.1016/j.reth.2024.06.009","DOIUrl":"https://doi.org/10.1016/j.reth.2024.06.009","url":null,"abstract":"<div><h3>Introduction</h3><p>Autologous mononuclear cells (MNCs) have been used in vascular regenerative therapy since the identification of endothelial progenitor cells (EPCs). However, the efficacy of autologous EPC therapy for diseases such as diabetes and connective tissue disorders is limited due to deficiencies in the number and function of EPCs. To address this, we developed a novel RE-01 cells that enriches pro-angiogenic cells from peripheral blood MNCs (PBMNCs).</p></div><div><h3>Methods</h3><p>PBMNCs were collected from healthy volunteers following ethical guidelines. RE-01 cells were cultured in the presence of specific growth factors for 5 days without media change. Flow cytometry was used to analyze cell surface markers. Tube formation assays, EPC culture assays, and mRNA analysis were performed to evaluate angiogenic potential. The efficacy of RE-01 cells upon transplantation into ischemic hind limbs of mice was evaluated.</p></div><div><h3>Results</h3><p>RE-01 cells exhibited a significant increase in pro-angiogenic cells such as M2 macrophages and angiogenic T cells, in contrast to PBMNCs, while the number of inflammatory cells reduced. <em>In vitro</em> assays demonstrated the enhanced angiogenic abilities of RE-01 cells, supported by increased mRNA expression of angiogenesis-related cytokines. <em>In vivo</em> studies using mouse ischemic hind limb models have shown that blood flow and angiogenesis improved following RE-01 cell transplantation. Transplantations for 3 consecutive days significantly improved the number of pericyte-recruited vessels in the severely ischemic hind limbs of mice.</p></div><div><h3>Conclusions</h3><p>RE-01 cells showed promising results in enhancing angiogenesis and arteriogenesis, possibly owing to the presence of M2 macrophages and angiogenic T cells. These cells also demonstrated anti-fibrotic effects. The efficacy of RE-01 cells has been confirmed in mouse models, suggesting their potential for treating ischemic vascular diseases. Clinical trials are planned to validate the safety and efficacy of RE-01 cell therapy in patients with connective tissue disease and unhealed ulcers. We hope that this new RE-01 cell therapy will prevent many patients from undergoing amputation.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 299-307"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001159/pdfft?md5=f81c17933c92e9c6bd16f02f88f6caf8&pid=1-s2.0-S2352320424001159-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical application of platelet rich plasma to promote healing of open hand injury with skin defect","authors":"Xinhui Du ,&nbsp;Jiarui Zhao ,&nbsp;Qian Ren ,&nbsp;Yibo Ma ,&nbsp;Pengxia Duan ,&nbsp;Yansheng Huang ,&nbsp;Sibo Wang","doi":"10.1016/j.reth.2024.06.003","DOIUrl":"https://doi.org/10.1016/j.reth.2024.06.003","url":null,"abstract":"<div><h3>Background</h3><p>Skin defects caused by open hand trauma are difficult to treat clinically and severely affect the recovery of hand function. Autologous platelet-rich plasma (PRP) has been widely used in the treatment of refractory chronic wounds, but its use in hand trauma skin defects remains scarce.</p></div><div><h3>Methods</h3><p>This study compared the outcomes of 27 patients treated with PRP to 31 patients undergoing skin flap transplantation for hand wounds. We assessed several parameters, including healing times, duration of surgery, postoperative pain (VAS score), intraoperative amputation length, finger function, sensation restoration, nail bed preservation, and hospitalization expenses.</p></div><div><h3>Results</h3><p>PRP-treated patients showed a mean healing time of 21.59 ± 3.17 days. Surgical times were significantly shorter in the PRP group (22.04 ± 7.04 min) compared to the flap group (57.45 ± 8.15 min, P &lt; 0.0001). PRP patients experienced longer postoperative healing times (20.15 ± 2.16 days) than those in the skin flap group (12.84 ± 1.08 days, P &lt; 0.0001), but reported lower pain scores (1.3 ± 1.44 vs 2.55 ± 2.06, P = 0.0119). Range of Motion (ROM) at the proximal interphalangeal joint was better in the PRP group (96.26° ± 6.69) compared to the flap group (86.16° ± 15.24, P = 0.0028). Sensory outcomes favored the PRP group, with a two-point discrimination of 2.37 ± 1.34 mm versus 2.52 ± 1.27 mm in the flap group (P = 0.0274). Costs were lower in the PRP group ($2081.6 ± 258.14 vs $2680.18 ± 481.15, P &lt; 0.0001).</p></div><div><h3>Conclusion</h3><p>PRP treatment for skin defects from hand trauma is effective, offering advantages in terms of reduced surgical time, pain, and cost, with comparable or superior functional outcomes to flap transplantation. Despite longer healing times, PRP may represent a preferable option for open hand injuries, preserving more nail beds and resulting in better sensation and joint motion.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 308-314"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235232042400110X/pdfft?md5=5bc3b69dbcb9bb6ee64bdf2d829fab81&pid=1-s2.0-S235232042400110X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141438956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human resources required in the field of regenerative medicine: A follow-up of the Japanese survey in 2015","authors":"Sachiko Ezoe","doi":"10.1016/j.reth.2024.07.003","DOIUrl":"10.1016/j.reth.2024.07.003","url":null,"abstract":"<div><p>In 2015, we conducted a survey of the corporate members of FIRM on the human resources and training required in the field of regenerative cell therapies and reported the results in this journal. After that, industrialization of regenerative medicine has progressed and some cell products have been approved, and infrastructures, such as laws and educational systems, have been improved. To capture the changing demands for human resources in response to the shift in social circumstances, we conducted another survey. Consequently, now, there is an increasing demand for highly specialized skills and knowledge in the field of regenerative medicine. Furthermore, it was found that QA/QC managers and specialists of pharmaceutical affairs are strongly demanded, rather than technicians of cell culture. In addition, it became evident that there are still relatively few companies that have established their own internal education systems, and, in most cases, employees are trained by senior stuff. The establishment of efficient education systems in public institutions and academic societies is desired.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 541-546"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001317/pdfft?md5=0da04e905124a28c6bc48e234c0fa593&pid=1-s2.0-S2352320424001317-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141950280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laminin 511 E8 fragment promotes to form basement membrane-like structure in human skin equivalents","authors":"Hitomi Fujisaki ,&nbsp;Takafumi Watanabe ,&nbsp;Shusuke Yoshihara ,&nbsp;Hideki Fukuda ,&nbsp;Yasuko Tomono ,&nbsp;Chisa Tometsuka ,&nbsp;Kazunori Mizuno ,&nbsp;Toshio Nishiyama ,&nbsp;Shunji Hattori","doi":"10.1016/j.reth.2024.08.014","DOIUrl":"10.1016/j.reth.2024.08.014","url":null,"abstract":"<div><h3>Introduction</h3><p>Laminin 511 (LM511), a component of the skin basement membrane (BM), is known to enhance the adhesion of some cell types and it has been reported to affect cell behavior. A recombinant fragment consisting of the integrin recognition site; E8 region of LM511 (511E8) has also been studied. 511E8 has been reported by many as a superior culture substrate. However, the effects of 511E8 on human skin cells remain unclear. In this study, we added 511E8 during the culture period of a reconstituted skin equivalent (SE) and investigated its effect on the formation of BM-like structures.</p></div><div><h3>Methods</h3><p>SEs were formed by air-liquid culture of human foreskin keratinocytes (HFKs) on contracted type I collagen (Col-I) gels containing human fibroblasts. We compared the BM-like structures formed with and without 511E8 during HFKs culture periods. Morphological analysis, gene expression analysis of extracellular matrix components, and localization analysis of 511E8 in order to identify where 511E8 works were performed.</p></div><div><h3>Results</h3><p>Immunohistochemical observation by light microscopy showed an accumulation of BM components between the gels and cell layers regardless of the addition of 511E8. There was a stronger and more continuous positive staining for LM α3, type IV collagen, and type VII collagen in the 511E8-added group compared to the no-added group. Transmission electron microscopic observation showed that the continuity of BM-like structures was increased with the addition of 511E8. Furthermore, gene expression analysis showed that the 511E8 addition increased some BM component genes expression, with collagen type IV and type VII α1 chains showing significant increases. His-tagged 511E8 was stained around the basal cells of HFK layers, not in basal regions. Co-staining with anti-His-tag and anti-integrin β1 antibodies revealed the co-localization of theses in some intercellular regions among basal cells.</p></div><div><h3>Conclusion</h3><p>These results suggest that 511E8 effected on HFKs, enhancing the production of BM components and strengthening the anchoring between the Col-I gels and the HFK layers.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 717-728"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001512/pdfft?md5=50c90658d304399936f559d494866043&pid=1-s2.0-S2352320424001512-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of a FOXO1 inhibitor on trophoblast differentiation from human pluripotent stem cells and ERV-associated gene expression","authors":"Erika Tanaka ,&nbsp;Michiyo Koyanagi-Aoi ,&nbsp;So Nakagawa ,&nbsp;Sayumi Shimode ,&nbsp;Hideto Yamada ,&nbsp;Yoshito Terai ,&nbsp;Takashi Aoi","doi":"10.1016/j.reth.2024.08.020","DOIUrl":"10.1016/j.reth.2024.08.020","url":null,"abstract":"<div><h3>Introduction</h3><p>In human placental development, the trophectoderm (TE) appears in blastocysts on day 5 post-fertilization and develops after implantation into three types of trophoblast lineages: cytotrophoblast (CT), syncytiotrophoblast (ST), and extravillous trophoblast (EVT). CDX2/Cdx2 is expressed in the TE, and Cdx2 expression is upregulated by knockdown of Foxo1 in mouse ESCs. However, the significance of FOXO1 in trophoblast lineage differentiation during the early developmental period remains unclear. In this study, we examined the effect of FOXO1 inhibition on the differentiation of naive human induced pluripotent stem cells (iPSCs) into TE and trophoblast lineages.</p></div><div><h3>Methods</h3><p>We induced TE differentiation from naive iPSCs in the presence or absence of a FOXO1 inhibitor, and the resulting cells were subjected to trophoblast differentiation procedures without the FOXO1 inhibitor. The cells obtained in these processes were assessed for morphology, gene expression, and hCG secretion using phase-contrast microscopy, reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR (RT-qPCR), RNA-seq, immunochromatography, and a chemiluminescent enzyme immunoassay.</p></div><div><h3>Results</h3><p>In the induction of trophoblast differentiation from naive iPSCs, treatment with a FOXO1 inhibitor resulted in the enhanced expression of TE markers, CDX2 and HAND1, but conversely decreased the expression of ST markers, such as ERVW1 (Syncytin-1) and GCM1, and an EVT marker, HLA-G. The proportion of cells positive for an early TE marker TACSTD2 and negative for a late TE marker ENPEP was higher in FOXO1 inhibitor-treated cells than in non-treated cells. The expressions of ERVW1 (Syncytin-1), ERVFRD-1 (Syncytin-2), and other endogenous retrovirus (ERV)-associated genes that have been reported to be expressed in trophoblasts were suppressed in the cells obtained by differentiating the TE cells treated with FOXO1 inhibitor.</p></div><div><h3>Conclusions</h3><p>Treatment with a FOXO1 inhibitor during TE induction from naive iPSCs promotes early TE differentiation but hinders the progression of differentiation into ST and EVT. The suppression of ERV-associated genes may be involved in this process.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 729-740"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001561/pdfft?md5=e231e861dc5c09a1e4c13c29d81d1944&pid=1-s2.0-S2352320424001561-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142151838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An ADSC-loaded dermal regeneration template promotes full-thickness wound healing","authors":"Jin Xu ,&nbsp;Xuelian Chen ,&nbsp;Jizhuang Wang ,&nbsp;Beibei Zhang ,&nbsp;Wenjia Ge ,&nbsp;Jiaqiang Wang ,&nbsp;Peilang Yang ,&nbsp;Yan Liu","doi":"10.1016/j.reth.2024.08.010","DOIUrl":"10.1016/j.reth.2024.08.010","url":null,"abstract":"<div><h3>Introduction</h3><p>Full-thickness wounds lead to delayed wound healing and scarring. Adipose-derived stem cell (ADSC) grafting promotes wound healing and minimizes scarring, but the low efficiency of grafting has been a challenge. We hypothesized that loading ADSCs onto a clinically widely used dermal regeneration template (DRT) would improve the efficacy of ADSC grafting and promote full-thickness wound healing.</p></div><div><h3>Methods</h3><p>ADSCs from human adipose tissue were isolated, expanded, and labeled with a cell tracker. Labeled ADSCs were loaded onto the DRT. The viability, the location of ADSCs on the DRT, and the abundance of ADSCs in the wound area were confirmed using CCK8 and fluorescence microscopy. Full-thickness wounds were created on Bama minipigs, which were applied with sham, ADSC, DRT, and ADSC-DRT. Wounds from the four groups were collected at the indicated time and histological analysis was performed. RNA-seq analysis was also conducted to identify transcriptional differences among the four groups. The identified genes by RNA-seq were verified by qPCR. Immunohistochemistry and western blotting were used to assess collagen deposition. In vitro, the supernatant of ADSCs was used to culture fibroblasts to investigate the effect of ADSCs on fibroblast transformation into myofibroblasts.</p></div><div><h3>Results</h3><p>ADSCs were successfully isolated, marked, and loaded onto the DRT. The abundance of ADSCs in the wound area was significantly greater in the ADSC-DRT group than in the ADSC group. Moreover, the ADSC-DRT group exhibited better wound healing with improved re-epithelialization and denser collagen deposition than the other three groups. The RNA-seq results suggested that the application of the integrated ADSC-DRT system resulted in the differential expression of genes mainly associated with extracellular matrix remodeling. In vivo, wounds from the ADSC-DRT group exhibited an earlier increase in type III collagen deposition and alleviated scar formation. ADSCs inhibited the transformation of fibroblasts into myofibroblasts, along with increased levels of CTGF, FGF, and HGF in the supernatant of ADSCs. Wounds from the ADSC-DRT group had up-regulated expressions of CTGF, HGF, FGF, and MMP3.</p></div><div><h3>Conclusion</h3><p>The integral of ADSC-DRT increased the efficacy of ADSC grafting, and promoted full-thickness wound healing with better extracellular matrix remodeling and alleviated scar formation.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 800-810"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001470/pdfft?md5=921b9cad842d8220b310a82be82f0523&pid=1-s2.0-S2352320424001470-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142172465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}