{"title":"USP13 overexpression in BMSCs enhances anti-apoptotic ability and guards against methylprednisolone-induced osteonecrosis in rats.","authors":"Yixin Jiang, Xiaoli Fan, Yaling Yu, Hongfan Ge, Chengyin Liu, Yanyan Zhang, Lingyun Yu, Wen Yin, Zhenlei Zhou","doi":"10.1093/stmcls/sxae069","DOIUrl":"10.1093/stmcls/sxae069","url":null,"abstract":"<p><p>Methylprednisolone (MPS) use is linked to increased cases of osteonecrosis of the femoral head (ONFH). Bone marrow mesenchymal stem cells (BMSCs) have shown potential for treating MPS-induced ONFH, but their effectiveness is limited by high apoptosis rates post-transplantation. We developed a pretreatment strategy for BMSCs to improve their viability. In a rat model of MPS-induced ONFH, we evaluated the effects of USP13 overexpression in BMSCs through micro-CT, HE staining, and TUNEL staining. USP13-overexpressing BMSCs significantly reduced ONFH severity compared to plain BMSCs and direct lentivirus injection. USP13 also protected BMSCs from MPS-induced apoptosis by modulating PTEN and reducing AKT phosphorylation. This led to decreased expression of apoptotic genes and proteins in USP13-overexpressing BMSCs. Our findings highlight USP13 as a promising target for enhancing BMSC survival and efficacy in treating MPS-induced ONFH.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491799","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":"The influence of biomimetic conditions on neurogenic and neuroprotective properties of dedifferentiated fat cells.","authors":"Klaudia Radoszkiewicz, Paulina Rybkowska, Magdalena Szymanska, Natalia Ewa Krzesniak, Anna Sarnowska","doi":"10.1093/stmcls/sxae066","DOIUrl":"10.1093/stmcls/sxae066","url":null,"abstract":"<p><p>In the era of a constantly growing number of reports on the therapeutic properties of dedifferentiated, ontogenetically rejuvenated cells and their use in the treatment of neurological diseases, the optimization of their derivation and long-term culture methods seem to be crucial. One of the solutions is seen in the use of dedifferentiated fat cells (DFATs) that are characterized by a greater homogeneity. Moreover, these cells seem to possess a higher expression of transcriptional factors necessary to maintain pluripotency (stemness-related transcriptional factors) as well as a greater ability to differentiate in vitro into 3 embryonic germ layers, and a high proliferative potential in comparison to adipose stem/stromal cells. However, the neurogenic and neuroprotective potential of DFATs is still insufficiently understood; hence, our research goal was to contribute to our current knowledge of the subject. To recreate the brain's physiological (biomimetic) conditions, the cells were cultured at 5% oxygen concentration. The neural differentiation capacity of DFATs was assessed in the presence of the N21 supplement containing the factors that are typically found in the natural environment of the neural cell niche or in the presence of cerebrospinal fluid and under various spatial conditions (microprinting). The neuroprotective properties of DFATs were assessed using the coculture method with the ischemically damaged nerve tissue.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685665","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}
STEM CELLSPub Date : 2024-12-06DOI: 10.1093/stmcls/sxae062
Lian Yi, Yewei Qu, Qi Zhang, Shanshan Shi, Fangqin Li, Changda Qu, Yushi Tang, Shirong Wen, Yujun Pan
{"title":"Enforced hematopoietic cell E-selectin/L-selectin ligand expression enhances bone marrow stromal cells homing and amelioration of cerebral ischemia-reperfusion injury via induction of prostaglandin E2.","authors":"Lian Yi, Yewei Qu, Qi Zhang, Shanshan Shi, Fangqin Li, Changda Qu, Yushi Tang, Shirong Wen, Yujun Pan","doi":"10.1093/stmcls/sxae062","DOIUrl":"10.1093/stmcls/sxae062","url":null,"abstract":"<p><p>Ischemic stroke (IS) is a significant and potentially life-threatening disease with limited treatment options, often resulting in severe disability. Bone marrow stromal cells (BMSCs) transplantation has exhibited promising neuroprotection following cerebral ischemia-reperfusion injury (CIRI). However, the effectiveness is hindered by their low homing rate when administered through the vein. In this study, we aimed to enhance the homing ability of BMSCs through lentivirus transfection to express fucosyltransferase 7. This glycosylation engineered CD44 on BMSCs to express hematopoietic cell E-selectin/L-selectin ligand (HCELL), which is the most potent E-selectin ligand. Following enforced HCELL expression, the transplantation of BMSCs was then evaluated in a middle cerebral artery occlusion model. Results showed that HCELL+BMSCs significantly ameliorated neurological deficits and reduced the volume of cerebral infarction. Furthermore, the transplantation led to a decrease in apoptosis by upregulating BCL-2 and downregulating BAX, also reduced the mRNA levels of inflammatory factors, such as interleukin-1β (IL-1β), IL-2, IL-6, and tumor necrosis factor-alpha (TNF-α) in the ischemic brain tissue. Notably, enforced HCELL expression facilitated the migration of BMSCs toward cerebral ischemic lesions and their subsequent transendothelial migration through the upregulation of PTGS-2, increased production of PGE2 and activation of VLA-4. In summary, our study demonstrates that transplantation of HCELL+BMSCs effectively alleviates CIRI, and that enforced HCELL expression enhances the homing of BMSCs to cerebral ischemic lesions and their transendothelial migration via PTGS-2/PGE2/VLA-4. These findings indicate that enforced expression of HCELL on BMSCs could serve as a promising therapeutic strategy for the treatment of ischemic stroke.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1070-1084"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370460","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}
STEM CELLSPub Date : 2024-12-06DOI: 10.1093/stmcls/sxae064
Ying Geng, Chen Bao, Yue Chen, Ziwei Yan, Fen Miao, Ting Wang, Yingyi Li, Lu Li, Wen Sun, Yan Xu
{"title":"NLRP3 deficiency improves bone healing of tooth extraction sockets through SMAD2/3-RUNX2-mediated osteoblast differentiation.","authors":"Ying Geng, Chen Bao, Yue Chen, Ziwei Yan, Fen Miao, Ting Wang, Yingyi Li, Lu Li, Wen Sun, Yan Xu","doi":"10.1093/stmcls/sxae064","DOIUrl":"10.1093/stmcls/sxae064","url":null,"abstract":"<p><p>Impaired bone healing following tooth extraction poses a significant challenge for implantation. As a crucial component of the natural immune system, the NLRP3 inflammasome is one of the most extensively studied pattern-recognition receptors, and is involved in multiple diseases. Yet, the role of NLRP3 in bone healing remains to be clarified. Here, to investigate the effect of NLRP3 on bone healing, we established a maxillary first molar extraction model in wild-type and NLRP3KO mice using minimally invasive techniques. We observed that NLRP3 was activated during the bone repair phase, and its depletion enhanced socket bone formation and osteoblast differentiation. Moreover, NLRP3 inflammasome activation was found to inhibit osteogenic differentiation in alveolar bone-derived mesenchymal stem cells (aBMSCs), an effect mitigated by NLRP3 deficiency. Mechanistically, we established that the SMAD2/3-RUNX2 signaling pathway is a downstream target of NLRP3 inflammasome activation, and SMAD2/3 knockdown partially reversed the significant decrease in expression of RUNX2, OSX, and ALP induced by NLRP3. Thus, our findings demonstrate that NLRP3 negatively modulates alveolar socket bone healing and contributes to the understanding of the NLRP3-induced signaling pathways involved in osteogenesis regulation.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1085-1099"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454403","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}
STEM CELLSPub Date : 2024-12-06DOI: 10.1093/stmcls/sxae053
Jiemin Wang, Yingying Zhou, Ellen Donohoe, Aoife Canning, Seyedmohammad Moosavizadeh, Aideen E Ryan, Thomas Ritter
{"title":"Immunomodulatory potential of cytokine-licensed human bone marrow-derived mesenchymal stromal cells correlates with potency marker expression profile.","authors":"Jiemin Wang, Yingying Zhou, Ellen Donohoe, Aoife Canning, Seyedmohammad Moosavizadeh, Aideen E Ryan, Thomas Ritter","doi":"10.1093/stmcls/sxae053","DOIUrl":"10.1093/stmcls/sxae053","url":null,"abstract":"<p><p>Cytokine(s) pre-activation/licensing is an effective way to enhance the immunomodulatory potency of mesenchymal stromal cells (MSCs). Currently, IFN-γ licensing received the most attention in comparison with other cytokines. After licensing human bone marrow-derived MSCs with pro-/anti-inflammatory cytokines IFN-γ, IL-1β, TNF-α, TGF-β1 alone or in combination, the in vitro immunomodulatory potency of these MSCs was studied by incubating with allogeneic T cells and macrophage-like THP-1 cells. In addition, immunomodulation-related molecules filtered by bioinformatics, complement 1 subcomponent (C1s), and interferon-induced GTP-binding protein Mx2 (MX2), were studied to verify whether to reflect the immunomodulatory potency. Herein, we reported that different cytokines cause different effects on the function of MSC. While TGF-β1 licensing enhances the capacity of MSCs to induce T cells with an immunosuppressive phenotype, IFN-γ-licensing strengthens the inhibitory effect of MSC on T cell proliferation. Both TGF-β1 and IFN-γ licensing can enhance the effect of MSC on reducing the expression of pro-inflammatory cytokines by M1 macrophage-like THP-1 cells. Interestingly, IFN-γ upregulates potential potency markers extracellular C1s and kynurenine (KYN) and intracellular MX2. These 3 molecules have the potential to reflect mesenchymal stromal cell immunomodulatory potency. In addition, we reported that there is a synergistic effect of TGF-β1 and IFN-γ in immunomodulation.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1040-1054"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102747","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}
STEM CELLSPub Date : 2024-12-06DOI: 10.1093/stmcls/sxae057
Guanhao Hong, Yulan Zhou, Shukai Yang, Shouquan Yan, Jiaxu Lu, Bo Xu, Zeyu Zhan, Huasheng Jiang, Bo Wei, Jiafeng Wang
{"title":"Metformin acts on miR-181a-5p/PAI-1 axis in stem cells providing new strategies for improving age-related osteogenic differentiation decline.","authors":"Guanhao Hong, Yulan Zhou, Shukai Yang, Shouquan Yan, Jiaxu Lu, Bo Xu, Zeyu Zhan, Huasheng Jiang, Bo Wei, Jiafeng Wang","doi":"10.1093/stmcls/sxae057","DOIUrl":"10.1093/stmcls/sxae057","url":null,"abstract":"<p><p>A general decline in the osteogenic differentiation capacity of human bone marrow mesenchymal stem cells (hBMSCs) in the elderly is a clinical consensus, with diverse opinions on the mechanisms. Many studies have demonstrated that metformin (MF) significantly protects against osteoporosis and reduces fracture risk. However, the exact mechanism of this effect remains unclear. In this study, we found that the decreased miR-181a-5p expression triggered by MF treatment plays a critical role in recovering the osteogenic ability of aging hBMSCs (derived from elderly individuals). Notably, the miR-181a-5p expression in hBMSCs was significantly decreased with prolonged MF (1000 μM) treatment. Further investigation revealed that miR-181a-5p overexpression markedly impairs the osteogenic ability of hBMSCs, while miR-181a-5p inhibition reveals the opposite result. We also found that miR-181a-5p could suppress the protein translation process of plasminogen activator inhibitor-1 (PAI-1), as evidenced by luciferase assays and Western blots. Additionally, low PAI-1 levels were associated with diminished osteogenic ability, whereas high levels promoted it. These findings were further validated in human umbilical cord mesenchymal stem cells (hUCMSCs). Finally, our in vivo experiment with a bone defects rat model confirmed that the agomiR-181a-5p (long-lasting miR-181a-5p mimic) undermined bone defects recovery, while the antagomiR-181a-5p (long-lasting miR-181a-5p inhibitor) significantly promoted the bone defects recovery. In conclusion, we found that MF promotes bone tissue regeneration through the miR-181a-5p/PAI-1 axis by affecting MSC osteogenic ability, providing new strategies for the treatment of age-related bone regeneration disorders.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1055-1069"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277717","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}
STEM CELLSPub Date : 2024-12-06DOI: 10.1093/stmcls/sxae060
Steffen J Sonnentag, Nagwa S M Ibrahim, Veronique Orian-Rousseau
{"title":"CD44: a stemness driver, regulator, and marker-all in one?","authors":"Steffen J Sonnentag, Nagwa S M Ibrahim, Veronique Orian-Rousseau","doi":"10.1093/stmcls/sxae060","DOIUrl":"10.1093/stmcls/sxae060","url":null,"abstract":"<p><p>Although the concept of cancer stem cells is still controversial, previous studies have shown that blood cancers, as well as specific types of solid cancers such as colorectal cancer, rely on stem cells during the onset of tumor growth and further tumor development. Moreover, resistance to therapeutic treatment in leukemias such as acute myeloid leukemia and in colorectal cancer can be attributed to a small population of cells with stemness properties known as minimal residual disease. In this review, we look back on the discovery of cancer stem cells and the contribution of the findings in blood cancer to a parallel discovery in solid cancers. We focus on CD44 as a stem cell marker, both in blood cancers and in several types of solid cancers, particularly of the gastrointestinal tract. This review highlights newly discovered molecular mechanisms of action of CD44 which indicate that CD44 has indeed a function in stemness, stem cell maintenance, and drug resistance. We attempt here to make the link between the functions of CD44 isoforms in stemness and their involvement in specific steps of tumor growth and metastasis.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1031-1039"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370458","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}
STEM CELLSPub Date : 2024-12-06DOI: 10.1093/stmcls/sxae059
{"title":"Correction to: Combination of Systemic Chemotherapy with Local Stem Cell Delivered S-TRAIL in Resected Brain Tumors.","authors":"","doi":"10.1093/stmcls/sxae059","DOIUrl":"10.1093/stmcls/sxae059","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1102"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386821","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}
STEM CELLSPub Date : 2024-12-06DOI: 10.1093/stmcls/sxae067
Robert Sackstein
{"title":"Enforced HCELL expression: empowering \"Step 1\" to optimize the efficacy of mesenchymal stem/stromal cell therapy for stroke and other clinical conditions.","authors":"Robert Sackstein","doi":"10.1093/stmcls/sxae067","DOIUrl":"10.1093/stmcls/sxae067","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1027-1030"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602140","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}
STEM CELLSPub Date : 2024-12-06DOI: 10.1093/stmcls/sxad043
{"title":"Correction: Immunomodulatory Functions of Adipose Mesenchymal Stromal/Stem Cell Derived From Donors With Type 2 Diabetes and Obesity on CD4 T Cells.","authors":"","doi":"10.1093/stmcls/sxad043","DOIUrl":"10.1093/stmcls/sxad043","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1101"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9626056","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}