Tarek Ziad Arabi, Yazan Almasry, Ailing Xue, Alfonso Eirin, Amir Lerman, Xiang-Yang Zhu, Lilach O Lerman
{"title":"Immune rejection of human mesenchymal stem cells compared to extracellular vesicles in mice with renal artery stenosis.","authors":"Tarek Ziad Arabi, Yazan Almasry, Ailing Xue, Alfonso Eirin, Amir Lerman, Xiang-Yang Zhu, Lilach O Lerman","doi":"10.1093/stcltm/szaf015","DOIUrl":"10.1093/stcltm/szaf015","url":null,"abstract":"<p><p>Renal artery stenosis (RAS) is the leading cause of secondary hypertension worldwide. However, current medical and surgical treatment modalities provide minimal benefits for kidney injury. Recent preclinical RAS models have demonstrated promising potential of human mesenchymal stem cells (MSC) and their daughter extracellular vesicles (EV) in improving murine renal function and attenuating inflammation. However, the extent and mechanisms underlying immune rejection of xenogeneic MSCs or EVs are yet undetermined. Therefore, adipose tissue was harvested from adult healthy patients. Adipose-derived MSCs were extracted and cultured, and EVs were isolated from their supernatants via ultra-centrifugation. Then, mice randomly assigned to RAS or sham surgery were divided into 6 groups: sham surgery, RAS, sham + MSC, RAS + MSC, sham + EV, and RAS + EV. Two weeks after intra-aortic injection of MSCs (5 × 105) or EVs (20 µg protein), we compared the intrarenal T-cell and macrophage accumulation, splenic B-cell numbers, circulating cytokines and anti-human antibodies levels among the groups. MSCs and EVs did not influence intrarenal immune cell infiltrations. However, MSCs significantly increased circulating anti-human antibodies. In the spleen, RAS + EV mice showed higher memory IgM+ B-cells but reduced CD19+ B-cells compared to RAS + MSC. In vitro T-cell recall assay showed that both MSCs and EVs exhibited reduced IFN-γ release upon re-stimulation, indicating an immunosuppressive effect. Therefore, xenogeneic MSCs induced a greater humoral response in mice, while EVs triggered a splenic cellular response, but neither elicits discernible kidney rejection. Our results provide key insights into the immunomodulatory mechanisms of MSCs and EVs and immune mechanisms underlying xenograft rejection.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 4","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080594","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":"Reprogramming of skin fibroblasts by 3D spheroid culture promotes peripheral nerve regeneration via the ID3/semaphorin7a pathway.","authors":"Xu Tan, Zhou Zhang, Xiaohui Cao, Langfan Qu, Yinchun Xiong, Huijuan Li, Yu Wang, Zelin Chen, Chunmeng Shi","doi":"10.1093/stcltm/szaf005","DOIUrl":"https://doi.org/10.1093/stcltm/szaf005","url":null,"abstract":"<p><p>Peripheral nerve injury remains an intractable clinical issue with high morbidity, causing an excessive burden on the economy and society. Peripheral nerve tissue engineering combined with nerve conduits and supporting seed cells is considered a promising strategy for treating of long nerve defects. However, supporting seed cell sources that are easily accessible, capable of rapid expansion, and do not require genetic intervention are still urgently needed. This study intended to clarify whether the easily accessible and rapid expansion skin fibroblasts are the ideal supporting seed cells and can be reprogrammed into neural progenitor-like cells (NPCs) by forcing them to grow into a three-dimensional (3D) spheroid morphology. Results showed that 3D spheroid mouse dermal fibroblasts (MDFs) exhibited neural cell-like properties and could efficiently induce dorsal root ganglion neurons to extend the neurites. Transplantation of 3D spheroid MDFs significantly accelerated the regeneration of the sciatic nerve and improved the motor function of rats after transection compared to monolayer MDFs. Mechanism studies revealed that 3D spheroid culture significantly upregulated the expressions of the inhibitor of DNA binding 3 (ID3) and the hypoxia-inducible factor-1α (HIF-1α). The upregulation of the inhibitor of DNA binding 3 in 3D spheroid MDFs plays a critical role in acquiring NPC properties. Meanwhile, the upregulated ID3 and HIF-1α could synergistically upregulate semaphorin7a expression, which finally improved the extending of nerve axon in vitro and in vivo. This study may shed new light on treatments for peripheral nerve injury.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 3","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982669","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":"Human umbilical cord mesenchymal stem cell-derived exosomes promote osteogenesis in glucocorticoid-induced osteoporosis through PI3K/AKT signaling pathway-mediated ferroptosis inhibition.","authors":"Zhi-Meng Zhao, Jia-Ming Ding, Yu Li, Da-Chuan Wang, Ming-Jie Kuang","doi":"10.1093/stcltm/szae096","DOIUrl":"https://doi.org/10.1093/stcltm/szae096","url":null,"abstract":"<p><p>Glucocorticoid-induced osteoporosis (GIOP), the most common cause of secondary osteoporosis, is characterized by significant bone loss, decreased bone quality, and increased fracture risk. The current treatments for GIOP have several drawbacks. Exosomes are vital for cellular processes. However, very few studies have focused on using human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXOs) for GIOP treatment. In vitro and in vivo dexamethasone was used to evaluate the therapeutic effects of hUCMSC-EXOs on GIOP. CCK-8 and EdU assays were used to evaluate cell viability and proliferation, respectively. We conducted an alkaline phosphatase activity assay, alizarin red staining, Western blotting, and real-time PCR to detect the effect on osteogenesis. TMT-labeled quantitative proteomic and bioinformatic analyses were performed. Furthermore, we performed Western blotting, immunofluorescence, reactive oxygen species assays, and lipid peroxidation assays to investigate the regulatory mechanism by which hUCMSC-EXOs affect cell proliferation and osteogenic differentiation. The in vivo effects of hUCMSC-EXOs were evaluated using micro-CT, hematoxylin, and eosin staining, and immunohistochemical staining. We found that hUCMSC-EXOs reversed the inhibitory effects of glucocorticoids on human bone marrow stromal cell (hBMSC) proliferation and osteogenic differentiation and demonstrated that hUCMSC-EXOs reversed GIOP via the PI3K/AKT signaling pathway, inhibiting lipid peroxidation in vitro and in vivo. HUCMSC-EXOs promote hBMSC osteogenesis through the PI3K/AKT signaling pathway, inhibit ferroptosis, and have therapeutic potential for GIOP in mice.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 3","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998106","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":"iPSC-derived retinal pigment epithelium: an in vitro platform to reproduce key cellular phenotypes and pathophysiology of retinal degenerative diseases.","authors":"Huirong Li, Ruchi Sharma, Kapil Bharti","doi":"10.1093/stcltm/szae097","DOIUrl":"10.1093/stcltm/szae097","url":null,"abstract":"<p><p>Retinal pigment epithelium (RPE) atrophy is a significant cause of human blindness worldwide, occurring in polygenic diseases such as age-related macular degeneration (AMD) and monogenic diseases such as Stargardt diseases (STGD1) and late-onset retinal degeneration (L-ORD). The patient-induced pluripotent stem cells (iPSCs)-derived RPE (iRPE) model exhibits many advantages in understanding the cellular basis of pathological mechanisms of RPE atrophy. The iRPE model is based on iPSC-derived functionally mature and polarized RPE cells that reproduce several features of native RPE cells, such as phagocytosis of photoreceptor outer segments (POS) and replenishment of visual pigment. When derived from patients, iRPE are able to recapitulate critical cellular phenotypes of retinal degenerative diseases, such as the drusen-like sub-RPE deposits in the L-ORD and AMD models; lipid droplets and cholesterol accumulation in the STGD1 and AMD models. The iRPE model has helped discover the unexpected role of RPE in understanding retinal degenerative diseases, such as a cell-autonomous function of ABCA4 in STGD1. The iRPE model has helped uncover the pathological mechanism of retinal degenerative diseases, including the roles of alternate complement cascades and oxidative stress in AMD pathophysiology, abnormal POS processing in STGD1 and L-ORD, and its association with lipid accumulation. These studies have helped better understand-the role of RPE in retinal degenerative diseases, and molecular mechanisms underlying RPE atrophy, and have provided a basis to discover therapeutics to target RPE-associated diseases.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898301","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}
Muhammad El-Shafeey, Kathleen Pappritz, Isabel Voss, Kapka Miteva, Alessio Alogna, Martina Seifert, Henry Fechner, Jens Kurreck, Karin Klingel, Marion Haag, Michael Sittinger, Carsten Tschöpe, Sophie Van Linthout
{"title":"Mitigating murine acute and chronic Coxsackievirus B3-induced myocarditis with human right atrial appendage-derived stromal cells.","authors":"Muhammad El-Shafeey, Kathleen Pappritz, Isabel Voss, Kapka Miteva, Alessio Alogna, Martina Seifert, Henry Fechner, Jens Kurreck, Karin Klingel, Marion Haag, Michael Sittinger, Carsten Tschöpe, Sophie Van Linthout","doi":"10.1093/stcltm/szae103","DOIUrl":"10.1093/stcltm/szae103","url":null,"abstract":"<p><p>We previously have shown the potential of human endomyocardial biopsy (EMB)-derived cardiac adherent proliferating cells (CardAPs) as a new cell-therapeutic treatment option for virus-induced myocarditis. To overcome the limited cell yield per EMB, CardAPs have been isolated from the human right atrial appendage (RAA) in view of allogeneic application and off-the-shelf use. We aimed to investigate the cardioprotective and immunomodulatory potential of RAA-CardAPs in experimental acute and chronic Coxsackievirus B3 (CVB3)-induced myocarditis upon injection in the viral and inflammatory phase. In the acute model, male C57BL6/J mice were intraperitoneally (i.p.) injected with the CVB3 Nancy strain or phosphate buffered saline (PBS). One day after infection, mice were intravenously (i.v.) injected with RAA-CardAPs, EMB-CardAPs (as reference cells) or PBS. For the chronic model, male Naval Medical Research Institute mice were i.p. injected with the CVB3 31-1-93 strain or PBS. Ten days after infection, mice were i.v. injected with RAA-CardAPs. Cardiac function was characterized, followed by harvest of the left ventricle (LV) and spleen for subsequent analysis, 7 and 28 days after CVB3 infection in the acute and chronic model, respectively. In the acute model, RAA-CardAPs decreased cardiac fibrosis and improved cardiac function in CVB3 mice. RAA-CardAPs mice exerted immunomodulatory effects as evidenced by lower LV chemokines expression (C-C motif ligand [CCL]2 and CCL7), CD68+ cells presence, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, tumor necrosis factor-α, and IL-6 mRNA expression. In the chronic model, RAA-CardAPs reduced cardiac fibrosis and the severity of myocarditis, associated with an improvement in LV function. We conclude that RAA-CardAPs represent a treatment strategy to reduce the development of acute and chronic CVB3-induced myocarditis.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 3","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664378","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}
Ying Tang, Jiaxi Cheng, Cynthia Huang, Ping Qiu, Jingxin Li, Yuqing Eugene Chen, Dogukan Mizrak, Bo Yang
{"title":"TGFBR3 dependent mechanism of TGFB2 in smooth muscle cell differentiation and implications for TGFB2-related aortic aneurysm.","authors":"Ying Tang, Jiaxi Cheng, Cynthia Huang, Ping Qiu, Jingxin Li, Yuqing Eugene Chen, Dogukan Mizrak, Bo Yang","doi":"10.1093/stcltm/szae101","DOIUrl":"10.1093/stcltm/szae101","url":null,"abstract":"<p><strong>Introduction: </strong>Pathogenic variants in canonical transforming growth factor β (TGFβ) signaling genes predispose patients to thoracic aortic aneurysm and dissection (TAAD), predominantly in aortic root. Although TAAD pathogenesis associated with TGFβ receptor defects is well characterized, distinct and redundant mechanisms of TGFβ isoforms in TAAD incidence and severity remain elusive.</p><p><strong>Objective: </strong>Here we examined the biological role of TGFB2 in smooth muscle cell (SMC) differentiation and investigated how TGFB2 defects can lead to regional TAAD manifestations.</p><p><strong>Methods: </strong>To characterize the role of TGFB2 in SMC differentiation and function, we employed human-induced pluripotent stem cell (hiPSC)-derived SMC differentiation, CRISPR/Cas9 gene editing, three-dimensional SMC constructs, and human aortic tissue samples.</p><p><strong>Results: </strong>Despite the similar effects of different TGFβ isoforms on hiPSC-derived SMC differentiation, siRNA experiments revealed that TGFB2 distinctively displays TGFBR3 dependence for signal transduction, an understudied TGFβ receptor in TAAD. Molecular evaluation of different thoracic aorta regions suggested TGFB2 and TGFBR3 enrichment in the aortic root tunica media. TGFB2 haploinsufficiency (TGFB2KO/+) and TGFB2 neutralization impaired the differentiation of second heart field-derived SMCs. TGFBR3KO/KO prevented the molecular rescue of TGFB2KO/+ by TGFB2 supplementation indicating the involvement of TGFBR3 in TGFB2-mediated SMC differentiation. Lastly, a missense TGFB2 variant (TGFB2G276R/+) caused mechanical defects in SMC tissue ring constructs that were rescued by TGFB2 supplementation or genetic correction.</p><p><strong>Conclusion: </strong>Our data suggests the distinct regulation and action of TGFB2 in SMCs populating the aortic root, while redundant activities of TGFβ isoforms provide implications about the milder TAAD aggressiveness of pathogenic TGFB2 variants.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 3","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731609","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}
Ching-Chung Liang, Steven W Shaw, Wu-Chiao Hsieh, Yung-Hsin Huang, Chu-Ya Liang, Tsong-Hai Lee
{"title":"Bladder dysfunction in hypoestrogenic rats with metabolic syndrome can be ameliorated after amniotic fluid stem cell treatment.","authors":"Ching-Chung Liang, Steven W Shaw, Wu-Chiao Hsieh, Yung-Hsin Huang, Chu-Ya Liang, Tsong-Hai Lee","doi":"10.1093/stcltm/szae100","DOIUrl":"10.1093/stcltm/szae100","url":null,"abstract":"<p><strong>Background: </strong>Bladder dysfunction may occur with high frequency in postmenopausal women with metabolic syndrome (MetS). This study evaluated the therapeutic effects of human amniotic fluid stem cells (hAFSCs) on bladder dysfunction in ovariectomized rats with MetS.</p><p><strong>Materials and methods: </strong>Forty-eight female rats were divided into 4 groups: normal control, ovariectomy (OVX), and OVX and MetS without (OVX + MetS) and with hAFSCs treatment (OVX + MetS + hAFSCs). We assessed cystometric parameters, serum biochemistry parameters, wall thickness of iliac artery, apoptotic cells and collagen volume in bladder tissues, and the expressions of purinergic and muscarinic receptors, apoptosis-associated mitochondrial proteins, and markers of inflammation, fibrosis, and oxidative stress at posttreatment 1 and 3 months.</p><p><strong>Results: </strong>OVX + MetS rats showed significant dysfunction of bladder storage, including reduced intercontraction intervals and bladder capacity, along with increased residual urine volume and nonvoiding contractions. There was a significant increase in iliac artery wall thickness, bladder collagen volume, and number of apoptotic cells. Also, there were elevated expressions of P2X3 purinergic and M2/M3 muscarinic receptors, pro-apoptotic proteins, and markers of inflammation, fibrosis, and oxidative stress, with a concurrent decrease in anti-apoptotic protein, Bcl-2. Treatment with hAFSCs helped restoring bladder function, ameliorating histological abnormalities, and reducing pathological markers at 1 and/or 3 months.</p><p><strong>Conclusion: </strong>These findings suggest that hAFSCs can effectively mitigate bladder dysfunction in rats with ovarian hormone deficiency and MetS by modulating oxidative stress and mitochondrial apoptotic pathways.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 3","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754545","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}
Francesca Giannuzzi, Angela Picerno, Silvia Maiullari, Francesca Montenegro, Antonella Cicirelli, Alessandra Stasi, Giuseppe De Palma, Vito Francesco Di Lorenzo, Giovanni Battista Pertosa, Paola Pontrelli, Michele Rossini, Nunzia Gallo, Luca Salvatore, Vincenzo Di Leo, Mariella Errede, Roberto Tamma, Domenico Ribatti, Loreto Gesualdo, Fabio Sallustio
{"title":"Unveiling spontaneous renal tubule-like structures from human adult renal progenitor cell spheroids derived from urine.","authors":"Francesca Giannuzzi, Angela Picerno, Silvia Maiullari, Francesca Montenegro, Antonella Cicirelli, Alessandra Stasi, Giuseppe De Palma, Vito Francesco Di Lorenzo, Giovanni Battista Pertosa, Paola Pontrelli, Michele Rossini, Nunzia Gallo, Luca Salvatore, Vincenzo Di Leo, Mariella Errede, Roberto Tamma, Domenico Ribatti, Loreto Gesualdo, Fabio Sallustio","doi":"10.1093/stcltm/szaf002","DOIUrl":"10.1093/stcltm/szaf002","url":null,"abstract":"<p><p>The rapidly developing field of renal spheroids and organoids has emerged as a valuable tool for modeling nephrotoxicity, kidney disorders, and kidney development. However, existing studies have relied on intricate and sophisticated differentiation protocols to generate organoids and tubuloids, necessitating the external administration of multiple growth factors within precise timeframes. In our study, we demonstrated that human adult renal progenitor cells (ARPCs) isolated from the urine of both healthy subjects and patients can form spheroids that naturally generated very long tubule-like structures. Importantly, the generation of these tubule-like structures is driven solely by ARPCs, without the need for the external use of chemokines or growth factors to artificially induce this process. These tubule-like structures exhibit the expression of structural and functional renal tubule markers and bear, in some cases, striking structural similarities to various nephron regions, including the distal convoluted tubule, the loop of Henle, and proximal convoluted tubules. Furthermore, ARPC spheroids express markers typical of pluripotent cells, such as stage-specific embryonic antigen 4 (SSEA4), secrete elevated levels of renin, and exhibit angiogenic properties. Notably, ARPCs isolated from the urine of patients with IgA nephropathy form spheroids capable of recapitulating the characteristic IgA1 deposition observed in this disease. These findings represent significant advancements in the field, opening up new avenues for regenerative medicine in the study of kidney development, mechanisms underlying renal disorders, and the development of regenerative therapies for kidney-related ailments.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 3","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743672","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}
Yumi Ohori-Morita, Amal Ashry, Kunimichi Niibe, Hiroshi Egusa
{"title":"Current perspectives on the dynamic culture of mesenchymal stromal/stem cell spheroids.","authors":"Yumi Ohori-Morita, Amal Ashry, Kunimichi Niibe, Hiroshi Egusa","doi":"10.1093/stcltm/szae093","DOIUrl":"10.1093/stcltm/szae093","url":null,"abstract":"<p><p>Mesenchymal stromal/stem cells (MSCs) are promising candidates for regenerative medicine owing to their self-renewal properties, multilineage differentiation, immunomodulatory effects, and angiogenic potential. MSC spheroids fabricated by 3D culture have recently shown enhanced therapeutic potential. MSC spheroids create a specialized niche with tight cell-cell and cell-extracellular matrix interactions, optimizing their cellular function by mimicking the in vivo environment. Methods for 3D cultivation of MSCs can be classified into 2 main forms: static suspension culture and dynamic suspension culture. Numerous studies have reported the beneficial influence of these methods on MSCs, which is displayed by increased differentiation, angiogenic, immunomodulatory, and anti-apoptotic effects, and stemness of MSC spheroids. Particularly, recent studies highlighted the benefits of dynamic suspension cultures of the MSC spheroids in terms of faster and more compact spheroid formation and the long-term maintenance of stemness properties. However, only a few studies have compared the behavior of MSC spheroids formed using static and dynamic suspension cultures, considering the significant differences between their culture conditions. This review summarizes the differences between static and dynamic suspension culture methods and discusses the biological outcomes of MSC spheroids reported in the literature. In particular, we highlight the advantages of the dynamic suspension culture of MSC spheroids and contemplate its future applications for various diseases.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907710","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}
Daniela Grimm, Thomas J Corydon, Jayashree Sahana, Luis Fernando González-Torres, Armin Kraus, Shannon Marchal, Petra M Wise, Ulf Simonsen, Marcus Krüger
{"title":"Recent studies of the effects of microgravity on cancer cells and the development of 3D multicellular cancer spheroids.","authors":"Daniela Grimm, Thomas J Corydon, Jayashree Sahana, Luis Fernando González-Torres, Armin Kraus, Shannon Marchal, Petra M Wise, Ulf Simonsen, Marcus Krüger","doi":"10.1093/stcltm/szaf008","DOIUrl":"10.1093/stcltm/szaf008","url":null,"abstract":"<p><p>The still young and developing space age, characterized by lunar and Martian exploration and the vision of extraterrestrial settlements, presents a unique environment to study the impact of microgravity (µg) on human physiology and disease development. Cancer research is currently a key focus of international space science, as µg fundamentally impacts cellular processes like differentiation, adhesion, migration, proliferation, survival, cell death, or growth of cancer cells as well as the cytoskeleton and the extracellular matrix (ECM). By creating three-dimensional (3D) tumor models in a µg-environment, like multicellular spheroids (MCS), researchers can expedite drug discovery and development, reducing the need for animal testing. This concise review analyses the latest knowledge on the influence of µg on cancer cells and MCS formation. We will focus on cells from brain tumors, lung, breast, thyroid, prostate, gastrointestinal, and skin cancer exposed to real (r-) and simulated (s-) µg-conditions.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"14 3","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658722","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}