Pablo J Ross, Marcelo D Goissis, João P N Martins, James L Chitwood, J Richard Pursley, Guilherme J M Rosa, Jose B Cibelli
{"title":"Blastocyst Cell Number and Allocation Affect the Developmental Potential and Transcriptome of Bovine Somatic Cell Nuclear Transfer Embryos.","authors":"Pablo J Ross, Marcelo D Goissis, João P N Martins, James L Chitwood, J Richard Pursley, Guilherme J M Rosa, Jose B Cibelli","doi":"10.1089/scd.2022.0292","DOIUrl":"https://doi.org/10.1089/scd.2022.0292","url":null,"abstract":"<p><p>Cloning cattle using somatic cell nuclear transfer (SCNT) is inefficient. Although the rate of development of SCNT embryos in vitro is similar to that of fertilized embryos, most fail to develop into healthy calves. In this study, we aimed to identify developmentally competent embryos according to blastocyst cell composition and perform transcriptome analysis of single embryos. Transgenic SCNT embryos expressing nuclear-localized HcRed gene at day 7 of development were imaged by confocal microscopy for cell counting and individually transferred to recipient heifers. Pregnancy rates were determined by ultrasonography. Embryos capable of establishing pregnancy by day 35 had an average of 117 ± 6 total cells, whereas embryos with an average of 128 ± 5 cells did not establish pregnancy (<i>P</i> < 0.05). A lesser average number of 41 ± 3 cells in the inner cell mass (ICM) also resulted in pregnancies (<0.05) than a greater number of 48 ± 2 cells in the ICM. Single embryos were then subjected to RNA sequencing for transcriptome analysis. Using weighted gene coexpression network analysis, we identified clusters of genes in which gene expression correlated with the number of total cells or ICM cells. Gene ontology analysis of these clusters revealed enriched biological processes in coenzyme metabolic process, intracellular signaling cascade, and glucose catabolic process, among others. We concluded that SCNT embryos with fewer total and ICM cell numbers resulted in greater pregnancy establishment rates and that these differences are reflected in the transcriptome of such embryos.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10198087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>Correction to:</i> In Vitro Transdifferentiation Potential of Equine Mesenchymal Stem Cells into Schwann-Like Cells, by Lucas Vinícius de Oliveira Ferreira et al. Stem Cells and Development 2023;32(13-14):422-432; doi: 10.1089/scd.2022.0274.","authors":"","doi":"10.1089/scd.2022.0274.correx","DOIUrl":"10.1089/scd.2022.0274.correx","url":null,"abstract":"","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11079606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10180761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiaqi Wang, Yi Huang, Chen Zhang, Yan Ruan, Yanping Tian, Fengsheng Wang, Yixiao Xu, Meng Yu, Jiangjun Wang, Yuda Cheng, Lianlian Liu, Ran Yang, Jiali Wang, Yi Yang, Jiaxiang Xiong, Yan Hu, Rui Jian, Bing Ni, Wei Wu, Junlei Zhang
{"title":"Identification and Functional Evaluation of Alternative Splice Variants of Dax1 in Mouse Embryonic Stem Cells.","authors":"Jiaqi Wang, Yi Huang, Chen Zhang, Yan Ruan, Yanping Tian, Fengsheng Wang, Yixiao Xu, Meng Yu, Jiangjun Wang, Yuda Cheng, Lianlian Liu, Ran Yang, Jiali Wang, Yi Yang, Jiaxiang Xiong, Yan Hu, Rui Jian, Bing Ni, Wei Wu, Junlei Zhang","doi":"10.1089/scd.2023.0037","DOIUrl":"10.1089/scd.2023.0037","url":null,"abstract":"<p><p>Dax1 (<i>Nr0b1</i>; Dosage-sensitive sex reversal-adrenal hypoplasia congenital on the X-chromosome gene-1) is an important component of the transcription factor network that governs pluripotency in mouse embryonic stem cells (ESCs). Functional evaluation of alternative splice variants of pluripotent transcription factors has shed additional insight on the maintenance of ESC pluripotency and self-renewal. Dax1 splice variants have not been identified and characterized in mouse ESCs. We identified 18 new transcripts of <i>Dax1</i> with putative protein-coding properties and compared their protein structures with known Dax1 protein (Dax1-472). The expression pattern analysis showed that the novel isoforms were cotranscribed with Dax1-472 in mouse ESCs, but they had transcriptional heterogeneity among single cells and the subcellular localization of the encoded proteins differed. Cell function experiments indicated that Dax1-404 repressed <i>Gata6</i> transcription and functionally replaced Dax1-472, while Dax1-38 and Dax1-225 partially antagonized Dax1-472 transcriptional repression. This study provided a comprehensive characterization of the Dax1 splice variants in mouse ESCs and suggested complex effects of Dax1 variants in a self-renewal regulatory network.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10207593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Apelin-Overexpressing Neural Stem Cells in Conjunction with a Silk Fibroin Nanofiber Scaffold for the Treatment of Traumatic Brain Injury.","authors":"Tianwen Li, Qisheng Tang, Jiaxin Xu, Xiangru Ye, Kezhu Chen, Junjie Zhong, Jianhong Zhu, Shijun Lu, Tongming Zhu","doi":"10.1089/scd.2023.0008","DOIUrl":"https://doi.org/10.1089/scd.2023.0008","url":null,"abstract":"<p><p>Traumatic brain injury (TBI), especially moderate or severe TBI, is one of the most devastating injuries to the nervous system, as the existing therapies for neurological defect repair have difficulty achieving satisfactory results. Neural stem cells (NSCs) therapy is a potentially effective treatment option, especially after specific genetic modifications and when used in combination with biomimetic biological scaffolds. In this study, tussah silk fibroin (TSF) scaffolds with interconnected nanofibrous structures were fabricated using a top-down method. We constructed the apelin-overexpressing NSCs that were cocultured with a TSF nanofiber scaffold (TSFNS) that simulated the extracellular matrix in vitro. To verify the therapeutic efficacy of engineered NSCs in vivo, we constructed TBI models and randomized the C57BL/6 mice into three groups: a control group, an NSC-ctrl group (transplantation of NSCs integrated on TSFNS), and an NSC-apelin group (transplantation of apelin-overexpressing NSCs integrated on TSFNS). The neurological functions of the model mice were evaluated in stages. Specimens were obtained 24 days after transplantation for immunohistochemistry, immunofluorescence, and western blot experiments, and statistical analysis was performed. The results showed that the combination of the TSFNS and apelin overexpression guided extension and elevated the proliferation and differentiation of NSCs both in vivo and in vitro. Moreover, the transplantation of TSFNS-NSCs-Apelin reduced lesion volume, enhanced angiogenesis, inhibited neuronal apoptosis, reduced blood-brain barrier damage, and mitigated neuroinflammation. In summary, TSFNS-NSC-Apelin therapy could build a microenvironment that is more conducive to neural repair to promote the recovery of injured neurological function.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10209723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Etv5a Suppresses Neural Progenitor Cell Proliferation by Inhibiting <i>sox2</i> Transcription.","authors":"Hung-Yu Shih, Hao-Yuan Chen, Yin-Cheng Huang, Tu-Hsueh Yeh, Yi-Chieh Chen, Yi-Chuan Cheng","doi":"10.1089/scd.2023.0005","DOIUrl":"https://doi.org/10.1089/scd.2023.0005","url":null,"abstract":"<p><p>Neural progenitor cells are self-renewable, proliferative, and multipotent cell populations that generate diverse types of neurons and glia to build the nervous system. Transcription factors play critical roles in regulating various cellular processes; however, the transcription factors that regulate the development of neural progenitors are yet to be identified. In the present study, we demonstrated that zebrafish <i>etv5a</i> is expressed in the neural progenitor cells of the neuroectoderm. Downregulation of endogenous Etv5a function by <i>etv5a</i> morpholino or an <i>etv5a</i> dominant-negative variant increased the proliferation of <i>sox2</i>-positive neural progenitor cells, accompanied by inhibition of neurogenesis and gliogenesis. These phenotypes in Etv5a-depleted embryos could be rescued by a co-injection with <i>etv5a</i> cRNA. Etv5a overexpression reduced <i>sox2</i> expression. Direct binding of Etv5a to the regulatory elements of <i>sox2</i> was affirmed by chromatin immunoprecipitation. These data revealed that Etv5a directly suppressed <i>sox2</i> expression to reduce the proliferation of neural progenitor cells. In addition, the expression of <i>foxm1</i>, a putative target gene of Etv5a and a direct upstream transcription factor of <i>sox2</i>, was upregulated in Etv5a-deficient embryos. Moreover, the suppression of Foxm1 function by the <i>foxm1</i> dominant-negative construct nullified the phenotype of upregulated <i>sox2</i> expression caused by Etv5a deficiency. Overall, our results indicated that Etv5a regulates the expression of <i>sox2</i> via direct binding to the <i>sox2</i> promoter and indirect regulation by inhibiting <i>foxm1</i> expression. Hence, we revealed the role of Etv5a in the transcriptional hierarchy that regulates the proliferation of neural progenitor cells.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10206825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of Macrophage Phenotype in the Vascularization of Prevascularized Human Bone Marrow Mesenchymal Stem Cell Sheets.","authors":"Rui Chen, Siqi Long, Lina Ren, Sen Xu, Xiaoning Liu, Jiamin Shi, Jiaxin Liu, Dongyang Ma, Ping Zhou, Liling Ren","doi":"10.1089/scd.2022.0268","DOIUrl":"https://doi.org/10.1089/scd.2022.0268","url":null,"abstract":"<p><p>With the development of tissue engineering and regenerative medicine, prevascularized bone marrow mesenchymal stem cell (BMSC) sheets have been regarded as a promising method for tissue regeneration. Furthermore, the inflammatory response is one of the main regulators of vascularization and the restoration of engineered tissue function; among them, macrophages and cytokines produced by them are considered to be the decisive factors of the downstream outcomes. This study investigated the effect of macrophages on the formation of microvascular-like structures of human umbilical vein endothelial cells (HUVECs) in BMSC sheets. First, a human monocytic leukemia cell line (THP-1 cells) was differentiated into derived macrophages (M0) with phorbol 12-myristate 13-acetate and further activated into proinflammatory macrophages (M1 macrophages) with interferon-γ and lipopolysaccharide or anti-inflammatory macrophages (M2 macrophages) with interleukin-4. Then, HUVECs and prevascularized sheets were treated with conditioned media (CM) from different macrophages, and the impact of macrophage phenotypes on vascularized network formation in prevascularized cell sheets was examined by hematoxylin and eosin staining, CD31 immunofluorescence staining and enzyme-linked immunosorbent assay. Our study showed that macrophages may guide the arrangement of endothelial cells through a paracrine pathway. Cell sheets that were cultured in the CM from M2 macrophages were thinner than those cultured in other media. At various time points, the levels of tumor necrosis factor alpha and vascular endothelial growth factor in prevascularized sheets cultured with CM(M1) was higher than that in sheets cultured with other media; however, the levels of platelet-derived growth factor in prevascularized sheets cultured with CM(M2) was higher than that in sheets cultured with other media. These findings suggest that the paracrine effect of macrophages can influence the formation of microvascular networks in prevascularized sheets by regulating the arrangement of cells, the thickness of the cell sheet and the secretion of cytokines related to angiogenesis. Macrophages with different phenotypes have unique effects on prevascularized sheets.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10341287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrew Powell, Nicole A Edwards, Hailey L M Hunter, Patti Kaiser, Andrew John Watson, Robert Cumming, Dean Harvey Betts
{"title":"Deletion of <i>p66Shc</i> Dysregulates ERK and STAT3 Activity in Mouse Embryonic Stem Cells, Enhancing Their Naive-Like Self-Renewal in the Presence of Leukemia Inhibitory Factor.","authors":"Andrew Powell, Nicole A Edwards, Hailey L M Hunter, Patti Kaiser, Andrew John Watson, Robert Cumming, Dean Harvey Betts","doi":"10.1089/scd.2022.0283","DOIUrl":"https://doi.org/10.1089/scd.2022.0283","url":null,"abstract":"<p><p>The ShcA adapter protein is necessary for early embryonic development. The role of ShcA in development is primarily attributed to its 52 and 46 kDa isoforms that transduce receptor tyrosine kinase signaling through the extracellular signal regulated kinase (ERK). During embryogenesis, ERK acts as the primary signaling effector, driving fate acquisition and germ layer specification. P66Shc, the largest of the ShcA isoforms, has been observed to antagonize ERK in several contexts; however, its role during embryonic development remains poorly understood. We hypothesized that p66Shc could act as a negative regulator of ERK activity during embryonic development, antagonizing early lineage commitment. To explore the role of p66Shc in stem cell self-renewal and differentiation, we created a <i>p66Shc</i> knockout murine embryonic stem cell (mESC) line. Deletion of <i>p66Shc</i> enhanced basal ERK activity, but surprisingly, instead of inducing mESC differentiation, loss of p66Shc enhanced the expression of core and naive pluripotency markers. Using pharmacologic inhibitors to interrogate potential signaling mechanisms, we discovered that p66Shc deletion permits the self-renewal of naive mESCs in the absence of conventional growth factors, by increasing their responsiveness to leukemia inhibitory factor (LIF). We discovered that loss of p66Shc enhanced not only increased ERK phosphorylation but also increased phosphorylation of Signal transducer and activator of transcription in mESCs, which may be acting to stabilize their naive-like identity, desensitizing them to ERK-mediated differentiation cues. These findings identify p66Shc as a regulator of both LIF-mediated ESC pluripotency and of signaling cascades that initiate postimplantation embryonic development and ESC commitment.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rosalind Franklin Society Proudly Announces the 2022 Award Recipient for <i>Stem Cells and Development</i>.","authors":"Gordana Vunjak-Novakovic","doi":"10.1089/scd.2023.29014.rfs2022","DOIUrl":"https://doi.org/10.1089/scd.2023.29014.rfs2022","url":null,"abstract":"","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10026380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiangjun Wang, Chen Zhang, Yi Huang, Yan Ruan, Yan Hu, Jiaqi Wang, Fengsheng Wang, Meng Yu, Yixiao Xu, Lianlian Liu, Yuda Cheng, Ran Yang, Yutong Dong, Jiali Wang, Yi Yang, Jiaxiang Xiong, Yanping Tian, Qiangguo Gao, Junlei Zhang, Rui Jian
{"title":"Parallel Genome-Wide CRISPR Screens to Identify State-Dependent Self-Renewal Regulators of Mouse Embryonic Stem Cells.","authors":"Jiangjun Wang, Chen Zhang, Yi Huang, Yan Ruan, Yan Hu, Jiaqi Wang, Fengsheng Wang, Meng Yu, Yixiao Xu, Lianlian Liu, Yuda Cheng, Ran Yang, Yutong Dong, Jiali Wang, Yi Yang, Jiaxiang Xiong, Yanping Tian, Qiangguo Gao, Junlei Zhang, Rui Jian","doi":"10.1089/scd.2023.0053","DOIUrl":"https://doi.org/10.1089/scd.2023.0053","url":null,"abstract":"<p><p>The pluripotency of embryonic stem cells (ESCs) is more accurately viewed as a continuous developmental process rather than a fixed state. However, the factors that play general or state-specific roles in regulating self-renewal in different pluripotency states remain poorly defined. In this study, parallel genome-wide CRISPR/Cas9 knockout (KO) screens were applied in ESCs cultured in the serum plus LIF (SL) and in the 2i plus LIF (2iL) conditions. The candidate genes were classified into seven groups based on their positive or negative effects on self-renewal, and whether this effect was general or state-specific for ESCs under SL and 2iL culture conditions. We characterized the expression and function of genes in these seven groups. The loss of function of novel pluripotent candidate genes <i>Usp28</i>, <i>Zfp598</i>, and <i>Zfp296</i> was further evaluated in mouse ESCs. Consistent with our screen, the knockout of <i>Usp28</i> promotes the proliferation of SL-ESCs and 2iL-ESCs, whereas <i>Zfp598</i> is indispensable for the self-renewal of ESCs under both culture conditions. The cell phenotypes of <i>Zfp296</i> KO ESCs under SL and 2iL culture conditions were different. Our work provided a valuable resource for dissecting the molecular regulation of ESC self-renewal in different pluripotency states.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10341746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ashlyn E Whitlock, Kamila Moskowitzova, Ina Kycia, David Zurakowski, Dario O Fauza
{"title":"Morphometric, Developmental, and Anti-Inflammatory Effects of Transamniotic Stem Cell Therapy (TRASCET) on the Fetal Heart and Lungs in a Model of Intrauterine Growth Restriction.","authors":"Ashlyn E Whitlock, Kamila Moskowitzova, Ina Kycia, David Zurakowski, Dario O Fauza","doi":"10.1089/scd.2023.0040","DOIUrl":"https://doi.org/10.1089/scd.2023.0040","url":null,"abstract":"<p><p>Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can attenuate placental inflammation and minimize intrauterine growth restriction (IUGR). We sought to determine whether MSC-based TRASCET could mitigate fetal cardiopulmonary effects of IUGR. Pregnant Sprague-Dawley dams were exposed to alternating 12-h hypoxia (10.5% O<sub>2</sub>) cycles in the last fourth of gestation. Their fetuses (<i>n</i> = 155) were divided into 4 groups. One group remained untreated (<i>n</i> = 42), while three groups received volume-matched intra-amniotic injections of either saline (sham; <i>n</i> = 34), or of syngeneic amniotic fluid-derived MSCs, either in their native state (TRASCET; <i>n</i> = 36) or \"primed\" by exposure to interferon-gamma and interleukin-1beta before administration in vivo (TRASCET-primed; <i>n</i> = 43). Normal fetuses served as additional controls (<i>n</i> = 30). Multiple morphometric and biochemical analyses were performed at term for select markers of cardiopulmonary development and inflammation previously shown to be affected by IUGR. Among survivors (75%; 117/155), fetal heart-to-body weight ratio was increased in both the sham and untreated groups (<i>P</i> < 0.001 for both) but normalized in the TRASCET and TRASCET-primed groups (<i>P</i> = 0.275, 0.069, respectively). Cardiac b-type natriuretic peptide levels were increased in all hypoxia groups compared with normal (<i>P</i> < 0.001), but significantly decreased from sham and untreated in both TRASCET groups (<i>P</i> < 0.0001-0.005). Heart tumor necrosis factor-alpha levels were significantly elevated in sham and TRASCET groups (<i>P</i> = 0.009, 0.002), but normalized in the untreated and TRASCET-primed groups (<i>P</i> = 0.256, 0.456). Lung transforming growth factor-beta levels were significantly increased in both sham and untreated groups (<i>P</i> < 0.001, 0.003), but normalized in both TRASCET groups (<i>P</i> = 0.567, 0.303). Similarly, lung endothelin-1 levels were elevated in sham and untreated groups (<i>P</i> < 0.001 for both), but normalized in both TRASCET groups (<i>P</i> = 0.367, 0.928). We conclude that TRASCET with MSCs decreases markers of fetal cardiac strain, insufficiency, and inflammation, as well as of pulmonary fibrosis and hypertension in the rodent model of IUGR.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10323816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}