Stem Cells Translational Medicine最新文献

{"title":"Correction to: NLRP3 and AIM2 inflammasomes expression is modified by LPS and titanium ions increasing the release of active IL-1β in alveolar bone-derived MSCs.","authors":"","doi":"10.1093/stcltm/szae068","DOIUrl":"10.1093/stcltm/szae068","url":null,"abstract":"","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1040-1042"},"PeriodicalIF":5.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-based therapy in the treatment of musculoskeletal diseases.","authors":"Justin Trapana, Jonathan Weinerman, Danny Lee, Anil Sedani, David Constantinescu, Thomas M Best, Francis J Hornicek, Joshua M Hare","doi":"10.1093/stcltm/szae049","DOIUrl":"10.1093/stcltm/szae049","url":null,"abstract":"<p><p>A limited number of tissues can spontaneously regenerate following injury, and even fewer can regenerate to a state comparable to mature, healthy adult tissue. Mesenchymal stem cells (MSCs) were first described in the 1960s-1970s by Friedenstein et al as a small population of bone marrow cells with osteogenic potential and abilities to differentiate into chondrocytes. In 1991, Arnold Caplan coined the term \"mesenchymal cells\" after identifying these cells as a theoretical precursor to bone, cartilage, tendon, ligament, marrow stroma, adipocyte, dermis, muscle, and connective tissues. MSCs are derived from periosteum, fat, and muscle. Another attractive property of MSCs is their immunoregulatory and regenerative properties, which result from crosstalk with their microenvironment and components of the innate immune system. Collectively, these properties make MSCs potentially attractive for various therapeutic purposes. MSCs offer potential in sports medicine, aiding in muscle recovery, meniscal tears, and tendon and ligament injuries. In joint disease, MSCs have the potential for chondrogenesis and reversing the effects of osteoarthritis. MSCs have also demonstrated potential application to the treatment of degenerative disc disease of the cervical, thoracic, and lumbar spine.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"959-978"},"PeriodicalIF":5.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A detailed survey of the murine limbus, its stem cell distribution, and its boundaries with the cornea and conjunctiva.","authors":"Lamia Nureen, Joanna Biazik, Michael Carnell, Nick Di Girolamo","doi":"10.1093/stcltm/szae055","DOIUrl":"10.1093/stcltm/szae055","url":null,"abstract":"<p><p>The narrow intersection between the cornea and conjunctiva, otherwise known as the limbus, is purported to harbor stem cells (SCs) that replenish the ocular surface epithelium throughout life. Damage to this site or depletion of its SCs can have dire consequences for eye health and vision. To date, various SC and keratin proteins have been used to identify the limbus, however, none could definitively mark its boundaries. Herein, we use the mouse as a model system to investigate whether structural and phenotypic features can be used to define the limbus and its boundaries with adjacent tissues. We demonstrate that differentially aligned blood and lymphatic vessels, intraepithelial nerves, and basal epithelial cellular and nuclei dimensions can be used as structural landmarks of the limbus. Identification of these features enabled approximation of the limbal expanse, which varied across distinct ocular surface quadrants, with the superior nasal and inferior temporal limbus being the widest and narrowest, respectively. Moreover, label-retaining SCs were unevenly distributed across the ocular circumference, with increased numbers in the superior temporal and inferior temporal moieties. These findings will heighten our current understanding of the SC niche, be beneficial for accurately predicting SC distribution to improve their isolation and devising efficacious cell therapies, and importantly, aid the ongoing search for novel SC markers.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1015-1027"},"PeriodicalIF":5.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling devitalization: its impact on immune response and ectopic bone remodeling from autologous and allogeneic callus mimics.","authors":"Leanne de Silva,Jeroen J J P van den Beucken,Antoine J W P Rosenberg,Alessia Longoni,Debby Gawlitta","doi":"10.1093/stcltm/szae063","DOIUrl":"https://doi.org/10.1093/stcltm/szae063","url":null,"abstract":"Endochondral bone regeneration is a promising approach in regenerative medicine. Callus mimics (CMs) are engineered and remodeled into bone tissue upon implantation. The long-term objective is to fabricate a sustainable off-the-shelf treatment option for patients. Devitalization was introduced to facilitate storage and using allogeneic (donor) cells would further propel the off-the-shelf approach. However, allogeneic CMs for bone regeneration pose a potential antigenicity concern. Here, we explored the impact of devitalization on antigenicity and osteoinductive bone formation when implanting syngeneic or allogeneic CM in a vital or devitalized state. For this, we implanted chondrogenically differentiated rat-derived mesenchymal stromal cells using an allogeneic immunocompetent ectopic rat model. Vital syngeneic CMs demonstrated the highest bone formation, and vital allogeneic CMs showed the lowest bone formation, while both devitalized CMs showed comparable intermediate levels of bone formation. Preceding bone formation, the level of tartrate-resistant acid phosphatase staining at 7 and 14 days was proportional to the level of eventual bone formation. No differences were observed for local innate immune responses at any time point before or after bone formation. In contrast, allogeneic CMs elicit a mild adaptive immune response, which still permits bone formation in an immunocompetent environment, albeit at a reduced rate compared to the autologous living counterpart. Overall, devitalization delays bone formation when autologous CMs are implanted, whereas it accelerates bone formation in allogeneic CMs, highlighting the potential of this approach for achieving off-the-shelf treatment.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"9 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoded cardiopoietic cell secretome linkage to heart repair biosignature.","authors":"Armin Garmany,D Kent Arrell,Satsuki Yamada,Ryounghoon Jeon,Atta Behfar,Sungjo Park,Andre Terzic","doi":"10.1093/stcltm/szae067","DOIUrl":"https://doi.org/10.1093/stcltm/szae067","url":null,"abstract":"Cardiopoiesis-primed human stem cells exert sustained benefit in treating heart failure despite limited retention following myocardial delivery. To assess potential paracrine contribution, the secretome of cardiopoiesis conditioned versus naïve human mesenchymal stromal cells was decoded by directed proteomics augmented with machine learning and systems interrogation. Cardiopoiesis doubled cellular protein output generating a distinct secretome that segregated the conditioned state. Altering the expression of 1035 secreted proteins, cardiopoiesis reshaped the secretome across functional classes. The resolved differential cardiopoietic secretome was enriched in mesoderm development and cardiac progenitor signaling processes, yielding a cardiovasculogenic profile bolstered by upregulated cardiogenic proteins. In tandem, cardiopoiesis enhanced the secretion of immunomodulatory proteins associated with cytokine signaling, leukocyte migration, and chemotaxis. Network analysis integrated the differential secretome within an interactome of 1745 molecules featuring prioritized regenerative processes. Secretome contribution to the repair signature of cardiopoietic cell-treated infarcted hearts was assessed in a murine coronary ligation model. Intramyocardial delivery of cardiopoietic cells improved the performance of failing hearts, with undirected proteomics revealing 50 myocardial proteins responsive to cell therapy. Pathway analysis linked the secretome to cardiac proteome remodeling, pinpointing 17 cardiopoiesis-upregulated secretome proteins directly upstream of 44% of the cell therapy-responsive cardiac proteome. Knockout, in silico, of this 22-protein secretome-dependent myocardial ensemble eliminated indices of the repair signature. Accordingly, in vivo, cell therapy rendered the secretome-dependent myocardial proteome of an infarcted heart indiscernible from healthy counterparts. Thus, the secretagogue effect of cardiopoiesis transforms the human stem cell secretome, endows regenerative competency, and upregulates candidate paracrine effectors of cell therapy-mediated molecular restitution.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"11 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142209278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current cell therapies for systemic lupus erythematosus.","authors":"Lan T M Dao, Thu Thuy Vu, Quyen Thi Nguyen, Van T Hoang, Thanh Liem Nguyen","doi":"10.1093/stcltm/szae044","DOIUrl":"10.1093/stcltm/szae044","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which multiple organs are damaged by the immune system. Although standard treatment options such as hydroxychloroquine (HCQ), glucocorticoids (GCs), and other immunosuppressive or immune-modulating agents can help to manage symptoms, they do not offer a cure. Hence, there is an urgent need for the development of novel drugs and therapies. In recent decades, cell therapies have been used for the treatment of SLE with encouraging results. Hematopoietic stem cell transplantation, mesenchymal stem cells, regulatory T (Treg) cell, natural killer cells, and chimeric antigen receptor T (CAR T) cells are advanced cell therapies which have been developed and evaluated in clinical trials in humans. In clinical application, each of these approaches has shown advantages and disadvantages. In addition, further studies are necessary to conclusively establish the safety and efficacy of these therapies. This review provides a summary of recent clinical trials investigating cell therapies for SLE treatment, along with a discussion on the potential of other cell-based therapies. The factors influencing the selection of common cell therapies for individual patients are also highlighted.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"859-872"},"PeriodicalIF":5.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional cultured human umbilical cord mesenchymal stem cells attenuate pulmonary fibrosis by improving the balance of mitochondrial fusion and fission.","authors":"Huifang Zhai, Mengqi Jiang, Yaqin Zhao, Yujie Wang, Haitong Zhang, Yunxia Ji, Xiaodong Song, Jinjin Zhang, Changjun Lv, Minge Li","doi":"10.1093/stcltm/szae051","DOIUrl":"10.1093/stcltm/szae051","url":null,"abstract":"<p><p>Pulmonary fibrosis is a kind of fibrotic interstitial pneumonia with poor prognosis. Aging, environmental pollution, and coronavirus disease 2019 are considered as independent risk factors for pulmonary fibrogenesis. Consequently, the morbidity and mortality striking continues to rise in recent years. However, the clinical therapeutic efficacy is very limited and unsatisfactory. So it is necessary to develop a new effective therapeutic approach for pulmonary fibrosis. Human umbilical cord mesenchymal stem cells (hucMSCs) are considered as a promising treatment for various diseases because of their multiple differentiation and immunomodulatory function. The key bottleneck in the clinical application of hucMSCs therapy is the high-quality and large-scale production. This study used FloTrix miniSpin bioreactor, a three-dimensional (3D) cell culture system, for large-scale expansion of hucMSCs in vitro, and proved 3D cultured hucMSCs inhibited the differentiation of fibroblasts into myofibroblasts and myofibroblasts proliferation and migration, leading to slow down the development of pulmonary fibrosis. Further mechanistic studies clarified that hucMSCs reduced the amount of binding between circELP2 and miR-630, resulting in blocking YAP/TAZ translocation from cytoplasm to nucleus. This condition inhibited mitochondrial fusion and promoted mitochondrial fission, and ultimately improved fusion/fission balance and cellular homeostasis. To sum up, this work clarified the anti-fibrosis and mechanism of hucMSCs cultured from the 3D FloTrix miniSpin bioreactor. We hope to provide new ideas and new methods for the clinical transformation and industrialization of hucMSCs therapy.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"912-926"},"PeriodicalIF":5.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitigation of supply chain challenges in cell therapy manufacturing: perspectives from the cord blood alliance.","authors":"Patrick Killela, Kieran Herrity, Ludwig Frontier, Roger Horton, Joanne Kurtzberg, Wouter Van't Hof","doi":"10.1093/stcltm/szae048","DOIUrl":"10.1093/stcltm/szae048","url":null,"abstract":"<p><p>Cellular therapies rely on highly specialized supply chains that often depend on single source providers. Public cord blood banks (CBB) manufacturing the first cell therapy to be highly regulated by the FDA and related international agencies are a prime example of being subject to this phenomenon. In addition to banking unrelated donor cord blood units for transplantation, CBBs also source and characterize starting materials for supply to allogeneic cell therapy developers that often employ customized technologies offered by just a small number of manufacturers. As such, these supply chains are especially sensitive to even minor changes which often result in potential major impacts. Regulations can shape supply chain efficiencies, both directly via the definition of restricted technology and process requirements and indirectly by steering strategic business decisions of critical supply or service providers. We present 3 current supply chain issues with different root causes that are swaying efficiencies in cord blood banking and beyond. Specifically, the shortage of Hespan, a common supplement used in cord blood processing, the decision by the provider to stop supporting medical device marking of the Sepax system broadly used in cord blood banking, and a new European ruling on phasing out plasticizers that are critical for providing flexibility to cord blood collection bags, are all threatening downstream supply chain issues for the biologics field. We discuss overcoming these hurdles through the prism of unified mitigation strategies, defined, and implemented by multi-factorial teams and stakeholders, to negotiate resolutions with providers and regulators alike.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"843-847"},"PeriodicalIF":5.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced radiation sensitivity, decreased DNA damage repair, and differentiation defects in airway stem cells derived from patients with chronic obstructive pulmonary disease.","authors":"Lorena Giuranno, Jolanda A F Piepers, Evelien Korsten, Reitske Borman, Gerarda van de Kamp, Dirk De Ruysscher, Jeroen Essers, Marc A Vooijs","doi":"10.1093/stcltm/szae043","DOIUrl":"10.1093/stcltm/szae043","url":null,"abstract":"<p><p>Radiation therapy (RT) is a common treatment for lung cancer. Still, it can lead to irreversible loss of pulmonary function and a significant reduction in quality of life for one-third of patients. Preexisting comorbidities, such as chronic obstructive pulmonary disease (COPD), are frequent in patients with lung cancer and further increase the risk of complications. Because lung stem cells are crucial for the regeneration of lung tissue following injury, we hypothesized that airway stem cells from patients with COPD with lung cancer might contribute to increased radiation sensitivity. We used the air-liquid interface model, a three-dimensional (3D) culture system, to compare the radiation response of primary human airway stem cells from healthy and patients with COPD. We found that COPD-derived airway stem cells, compared to healthy airway stem cell cultures, exhibited disproportionate pathological mucociliary differentiation, aberrant cell cycle checkpoints, residual DNA damage, reduced survival of stem cells and self-renewal, and terminally differentiated cells post-irradiation, which could be reversed by blocking the Notch pathway using small-molecule γ-secretase inhibitors. Our findings shed light on the mechanisms underlying the increased radiation sensitivity of COPD and suggest that airway stem cells reflect part of the pathological remodeling seen in lung tissue from patients with lung cancer receiving thoracic RT.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"927-939"},"PeriodicalIF":5.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: EPHA2 is a novel cell surface marker of OCT4-positive undifferentiated cells during the differentiation of mouse and human pluripotent stem cells.","authors":"","doi":"10.1093/stcltm/szae054","DOIUrl":"10.1093/stcltm/szae054","url":null,"abstract":"","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"940"},"PeriodicalIF":5.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}