Stem cells and development最新文献

{"title":"Deer Antler Reserve Mesenchyme Cell-Conditioned Medium Reduces the Destruction of Periodontitis in Mice.","authors":"Hongbing Lin,&nbsp;Zhen Chen,&nbsp;Qianqian Guo,&nbsp;Peipei Zhang,&nbsp;Yue Tian,&nbsp;Huishan Chen,&nbsp;Haiping Zhao,&nbsp;Yuqin Shen","doi":"10.1089/scd.2022.0110","DOIUrl":"https://doi.org/10.1089/scd.2022.0110","url":null,"abstract":"<p><p>Reserve mesenchyme cells (RMCs) are a type of antler stem cells (ASCs) that contribute to the rapid growth of deer antlers, the only known mammalian organ that can fully regenerate annually. Based on the prior evidence, ASC-conditioned medium could improve regenerative cutaneous healing in rats. The purpose of the study was to evaluate the therapeutic effects of RMC-conditioned medium (RMC-CM) on reducing the destruction in the mice periodontitis (PD) model and the underlying mechanisms. The lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used in vitro to verify the effects of RMC-CM. The results revealed that RMC-CM could significantly reduce bone resorption and osteoclast activation, upregulate anti-inflammatory macrophages (M2) related interleukin (IL)-10 and CD206, and downregulate pro-inflammatory macrophages (M1) related tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase in vivo. In vitro, RMC-CM could significantly promote LPS-stimulated RAW264.7 cells migration, reduce osteoclast differentiation, downregulate the expression of TNF-α, IL-6, and IL-1β, and upregulate the expression of IL-10 and arginase 1. According to the results, we concluded that RMC-CM could significantly reduce alveolar bone resorption and inhibit inflammation in gingival tissue by decreasing the activation of osteoclasts and inducing macrophage polarization toward the M2 phenotype. This study may serve as the experimental foundation for RMC-CM in the treatment of PD.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10536015","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":"miR-1275 Inhibits Human Omental Adipose-Derived Stem Cells Differentiation Toward the Beige Phenotype via <i>PRDM16</i>.","authors":"Chenhong Lin,&nbsp;Xiaoying He,&nbsp;Xueying Chen,&nbsp;Liehua Liu,&nbsp;Hongyu Guan,&nbsp;Haipeng Xiao,&nbsp;Yanbing Li","doi":"10.1089/scd.2022.0176","DOIUrl":"https://doi.org/10.1089/scd.2022.0176","url":null,"abstract":"<p><p>Beige adipocytes have recently attracted attention for their potential as new therapeutic targets in the management of obesity and related metabolic disorders. MicroRNAs (miRNAs) have been reported as transcriptional regulators or biomarkers of brown and beige adipogenesis. Nevertheless, the effects of miRNAs involved in beige differentiation of human visceral adipocytes remain to be investigated. In this study, microarray screening showed that miR-1275 was significantly decreased during the differentiation of beige adipocytes induced by human omental adipose-derived stem cells (hASCs). Overexpression of miR-1275 suppressed the \"brown-like\" differentiation of hASCs by inhibiting the key transcriptional factor PR domain containing 16 (<i>PRDM16</i>) without affecting the proliferation. Adipogenesis and mitochondrial biogenesis of beige adipocytes derived from hASCs were impaired by miR-1275 overexpression. The regulatory effect of miR-1275 was determined by direct binding to the 3'-untranslated region of <i>PRDM16</i>, which was demonstrated by a dual-luciferase assay. Taken together, this study identified miR-1275 as a negative regulator of beige cell development in hASCs by inhibiting <i>PRDM16</i>. Thus, miR-1275 might be a potential target in the management of visceral obesity and related metabolic diseases.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10732624","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":"Three-Dimensional Culture of Equine Bone Marrow-Derived Mesenchymal Stem Cells Enhances Anti-Inflammatory Properties in a Donor-Dependent Manner.","authors":"Sophie H Bogers,&nbsp;Jennifer G Barrett","doi":"10.1089/scd.2022.0074","DOIUrl":"https://doi.org/10.1089/scd.2022.0074","url":null,"abstract":"<p><p>Three-dimensional (3D) culture of human mesenchymal stem cells (MSCs) as spheroids enhances the production of important regulators of inflammation: prostaglandin E2 (PGE₂), interleukin (IL)-6, and tumor necrosis factor-inducible gene 6 (TSG-6). The horse is a model species and suffers from musculoskeletal, ocular, and systemic inflammatory disease. It is unknown if 3D culture promotes enhanced production of immunomodulatory cytokines and regulators in equine MSCs and if there is variation between individual cell donors. We evaluated the feasibility, cell viability, and stem cell marker stability of 3D-cultured equine bone marrow-derived MSCs (eBMSCs) and determined the effect of inflammatory stimulation upon gene expression and secretion of key regulators of inflammation [PGE₂, TSG-6, IL-10, IL-6, stromal cell-derived factor 1 (SDF-1)]. Variations in anti-inflammatory phenotype between six donors were investigated, with and without IL-1β stimulation, in either monolayer [two-dimensional (2D)] or 3D culture. Our results showed that eBMSCs self-aggregate in 3D culture while maintaining cell viability and markers of stemness CD90, CD44, CD104, and Oct4. In addition, 3D culture enhances the anti-inflammatory phenotype regardless of inflammatory stimulation by increasing PGE₂, IL-6, TSG-6, SDF-1, and IL-10. Finally, anti-inflammatory phenotype was enhanced by IL-1β exposure but showed significant variation between cell lines in the degree of gene upregulation, and what genes were expressed. We conclude that 3D culture of eBMSCs as spheroids alters their anti-inflammatory phenotype, but this effect is influenced by cytokine exposure and cell donor.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10348430","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":"Suppressor of Fused Regulation of Hedgehog Signaling is Required for Proper Astrocyte Differentiation.","authors":"Danielle M Spice,&nbsp;Joshua Dierolf,&nbsp;Gregory M Kelly","doi":"10.1089/scd.2022.0131","DOIUrl":"https://doi.org/10.1089/scd.2022.0131","url":null,"abstract":"<p><p>Hedgehog signaling is essential for vertebrate development; however, less is known about the negative regulators that influence this pathway. Using the mouse P19 embryonal carcinoma cell model, suppressor of fused (SUFU), a negative regulator of the Hedgehog (Hh) pathway, was investigated during retinoic acid (RA)-induced neural differentiation. We found Hh signaling increased activity in the early phase of differentiation, but was reduced during terminal differentiation of neurons and astrocytes. This early increase in pathway activity was required for neural differentiation; however, it alone was not sufficient to induce neural lineages. SUFU, which regulates signaling at the level of Gli, remained relatively unchanged during differentiation, but its loss through CRISPR-Cas9 gene editing resulted in ectopic expression of Hh target genes. Interestingly, these SUFU-deficient cells were unable to differentiate toward neural lineages without RA, and when directed toward these lineages, they showed delayed and decreased astrocyte differentiation; neuron differentiation was unaffected. Ectopic activation of Hh target genes in SUFU-deficient cells remained throughout RA-induced differentiation and this was accompanied by the loss of Gli3, despite the presence of the <i>Gli3</i> message. Thus, the study indicates the proper timing and proportion of astrocyte differentiation requires SUFU, likely acting through Gli3, to reduce Hh signaling during late-stage differentiation.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10383441","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":"Overexpression of NDST1 Attenuates Fibrotic Response in Murine Adipose-Derived Stem Cells.","authors":"Takayoshi Otsuka, Ho-Man Kan, Timothy D Mason, Lakshmi S Nair, Cato T Laurencin","doi":"10.1089/scd.2022.0053","DOIUrl":"10.1089/scd.2022.0053","url":null,"abstract":"Adipose-derived stem cells (ADSCs) hold tremendous potential for treating diseases and repairing damaged tissues. Heparan sulfate (HS) plays various roles in cellular signaling mechanisms. The importance of HS in stem cell function has been reported and well documented. However, there has been little progress in using HS for therapeutic purposes. We focused on one of the sulfotransferases, NDST1, which influences overall HS chain extent and sulfation pattern, with the expectation to enhance stem cell function by increasing the N-sulfation level. We herein performed transfections of a GFP-vector control and NDST1-vector into mouse ADSCs to evaluate stem cell functions. Overexpression of NDST1 suppressed the osteogenic differentiation of ADSCs. There was no pronounced effect observed on the stemness, inflammatory gene expression, nor any noticeable effect in adipogenic and chondrogenic differentiation. Under the tumor necrosis factor-alpha (TNF-α) stimulation, NDST1 overexpression induced several chemokine productions that attract neutrophils and macrophages. Finally, we identified an anti-fibrotic response in ADSCs overexpressing NDST1. This study provides a foundation for the evaluation of HS-related effects in ADSCs undergoing ex vivo gene manipulation.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9836701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9374847","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}

{"title":"Laminin-511 Activates the Human Induced Pluripotent Stem Cell Survival via α6β1 Integrin-Fyn-RhoA-ROCK Signaling.","authors":"Yoshiki Nakashima,&nbsp;Masayoshi Tsukahara","doi":"10.1089/scd.2022.0010","DOIUrl":"https://doi.org/10.1089/scd.2022.0010","url":null,"abstract":"<p><p>In human induced pluripotent stem cells (hiPSCs), laminin-511/α6β1 integrin interacts with E-cadherin, an intercellular adhesion molecule, to induce the activation of the phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway. The interaction between laminin-511/α6β1 integrin and E-cadherin, an intercellular adhesion molecule, results in protection against apoptosis through the proto-oncogene tyrosine-protein kinase Fyn(Fyn)-RhoA-ROCK signaling pathway and the Ras homolog gene family member A (RhoA)/Rho kinase (ROCK) signaling pathway (the major pathway for cell death). In this article, the impact of laminin-511 on hiPSC on α6β1 integrin-Fyn-RhoA-ROCK signaling is discussed and explored along with validation experiments. <i>PIK3CA</i> mRNA (mean [standard deviation {SD}]: iMatrix-511, 1.00 [0.61]; collagen+MFGE8, 0.023 [0.02]; **<i>P</i> < 0.01; <i>n</i> = 6) and <i>PIK3R1</i> mRNA (mean [SD]: iMatrix-511, 1.00 [0.79]; collagen+MFGE8, 0.040 [0.06]; *<i>P</i> < 0.05; <i>n</i> = 6) were upregulated by iMatrix-511 resulting from an increased expression of <i>Integrin α6</i> mRNA (mean [SD]: iMatrix-511, 1.00 [0.42]; collagen+MFGE8, 0.23 [0.05]; **<i>P</i> < 0.01; <i>n</i> = 6). The iMatrix-511 increased the expression of p120-<i>Catenin</i> mRNA (mean [SD]: iMatrix-511, 1.00 [0.71]; collagen+MFGE8, 0.025 [0.03]; **<i>P</i> < 0.01; <i>n</i> = 6) and <i>RAC1</i> mRNA (mean [SD]: iMatrix-511, 1.00 [0.28]; collagen+MFGE8, 0.39 [0.15]; **<i>P</i> < 0.01; <i>n</i> = 6) by increasing the expression of <i>E-cadherin</i> mRNA (mean [SD]: iMatrix-511, 1.00 [0.38]; collagen+MFGE8, 0.16 [0.11]; **<i>P</i> < 0.01; <i>n</i> = 6). As a result, iMatrix-511 increased the expression of P190 <i>RhoGAP</i> (<i>GTPase-activating proteins</i>) mRNA, such as <i>ARHGAP1</i> mRNA (mean [SD]: iMatrix-511, 1.00 [0.57]; collagen+MFGE8, 0.032 [0.03]; **<i>P</i> < 0.01; <i>n</i> = 6), ARHGAP4 mRNA (mean [SD]: iMatrix-511, 1.00 [0.56]; collagen+MFGE8, 0.039 [0.049]; **<i>P</i> < 0.01; <i>n</i> = 6), and <i>ARHGAP5</i> mRNA (mean [SD]: iMatrix-511, 1.00 [0.39]; collagen+MFGE8, 0.063 [0.043]; **<i>P</i> < 0.01; <i>n</i> = 6). Western blotting showed that phospho-Rac1 remained in the cytoplasm and phospho-Fyn showed nuclear transition in iPSCs cultured on iMatrix-511. Proteome analysis showed that PI3K signaling was enhanced and cytoskeletal actin was activated in iPSCs cultured on iMatrix-511. In conclusion, laminin-511 strongly activated the cell survival by promoting α6β1 integrin-Fyn-RhoA-ROCK signaling in hiPSCs.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9700348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10689871","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}

{"title":"Effects of Recloning on the Telomere Lengths of Mouse <i>Terc</i>^<i>+/-</i> Nuclear Transfer-Derived Embryonic Stem Cells.","authors":"Li-Kuang Tsai,&nbsp;Huan Ou-Yang,&nbsp;Jie Xu,&nbsp;Chuan-Mu Chen,&nbsp;Wei-Fang Chang,&nbsp;Li-Ying Sung","doi":"10.1089/scd.2022.0115","DOIUrl":"https://doi.org/10.1089/scd.2022.0115","url":null,"abstract":"<p><p>Haploinsufficiency of genes that participate in telomere elongation and maintenance processes, such as telomerase RNA component (<i>Terc</i>) and telomere reverse transcriptase (<i>Tert</i>), often leads to premature aging-related diseases such as dyskeratosis congenita and aplastic anemia. Previously, we reported that when mouse <i>Terc</i>^+/- tail tip fibroblasts (TTFs) were used as donor cells for somatic cell nuclear transfer (SCNT, also known as cloning), the derivative embryonic stem cells (ntESCs) had elongated telomeres. In the present work, we are interested to know if an additional round of SCNT, or recloning, could lead to further elongation of telomeres. <i>Terc</i>^+/- TTFs were used to derive the first-generation (G1) ntESCs, followed by a second round of SCNT using G1-<i>Terc</i>^+/- ntESCs as donor cells to derive G2-<i>Terc</i>^+/- ntESCs. Multiple lines of G1- and G2-<i>Terc</i>^+/- ntESCs were efficiently established, and all expressed major pluripotent markers and supported efficient chondrocyte differentiation in vitro. Compared with donor TTFs, telomere lengths of G1 ntESCs were elongated to the level comparable with that in wild-type ntESCs. Interestingly, recloning did not further elongate the telomere lengths of <i>Terc</i>^+/- ntESCs. Together, our work demonstrates that while a single round of SCNT is a viable means to reprogram <i>Terc</i> haploinsufficient cells to the ESC state, and to elongate these cells' telomere lengths, a second round of SCNT does not necessarily further elongate the telomeres.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10332973","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":"Comparison Between Cancellous Trabecular and Cortical Specimens from Human Lumbar Spine Samples as an Alternative Source of Mesenchymal Stromal Cells.","authors":"Stefania Lenna,&nbsp;Ava Brozovich,&nbsp;Takashi Hirase,&nbsp;Francesca Paradiso,&nbsp;Bradley K Weiner,&nbsp;Francesca Taraballi","doi":"10.1089/scd.2022.0157","DOIUrl":"https://doi.org/10.1089/scd.2022.0157","url":null,"abstract":"<p><p>Due to their immunosuppressive potential and ability to differentiate into multiple musculoskeletal cell lineages, mesenchymal stromal cells (MSCs) became popular in clinical trials for the treatment of musculoskeletal disorders. The aim of this study was to isolate and characterize native populations of MSCs from human cortical and cancellous bone from the posterior elements of the lumbar spine and determine what source of MSCs yields better quality and quantity of cells to be potentially used for spinal fusion repair. We were able to show that MSCs from trabecular and cortical spine had the typical MSC morphology and expression markers; the ability to differentiate in adipocyte, chondrocyte, or osteoblast but they did not have a consistent pattern in the expression of the specific differentiation lineage genes. Moreover, MSCs from both sites demonstrated an immune suppression profile suggesting that these cells may have a more promising success in applications related to immunomodulation more than exploring their ability to drive osteogenesis to prevent nonunion in spine fusion procedures.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10346031","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":"Cell Surface Accumulation of Intracellular Leucine Proline-Enriched Proteoglycan 1 Enhances Odontogenic Potential of Human Dental Pulp Stem Cells.","authors":"Kyung-Jung Kang,&nbsp;Min-Jeong Choi,&nbsp;Tae-Jun Min,&nbsp;Tae Min You,&nbsp;Gyutae Lee,&nbsp;Seon-Yle Ko,&nbsp;Young-Joo Jang","doi":"10.1089/scd.2022.0174","DOIUrl":"https://doi.org/10.1089/scd.2022.0174","url":null,"abstract":"<p><p>Primary dental pulp cells can be differentiated into odontoblast-like cells, which are responsible for dentin formation and mineralization. Successful differentiation of primary dental pulp cells can be verified using a few markers. However, odontoblast-specific cell surface markers have not been fully studied yet. LEucine PRoline-Enriched Proteoglycan 1 (LEPRE1) is a basement membrane-associated proteoglycan. LEPRE1 protein levels are increased during odontoblastic differentiation of human dental pulp cells (hDPCs). Intracellular and cell surface accumulation of this protein completely disappeared during dentin maturation and mineralization. Cell surface binding of an anti-LEPRE1 monoclonal antibody that could recognize an extracellular region was gradually increased in the odontoblastic stage. Overexpression and knockdown experiments showed that accumulation of intracellular LEPRE1 could lead to inefficient odontoblastic differentiation and that the movement of LEPRE1 from intracellular region to the cell surface was required for odontoblastic differentiation. Indeed, when LEPRE1 already located on the cell surface was blocked by the anti-LEPRE1 monoclonal antibody, odontoblastic differentiation of hDPCs was inhibited. In this study, we looked at other aspects of LEPRE1 function as a cell surface molecule rather than its known intracellular hydroxylase activity. Our results indicate that this protein has potential as a specific cell surface marker in odontoblastic differentiation.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10341056","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":"Proteomic Analysis of Retinal Conditioned Medium: The Effect on Early Differentiation of Embryonic Stem Cells into Retina.","authors":"Shudi Mao,&nbsp;Aiwen Miao,&nbsp;Yamei Cui,&nbsp;Jing Lu,&nbsp;Jianying Pan,&nbsp;Yishen Wang,&nbsp;Yiwen Hong,&nbsp;Yan Luo","doi":"10.1089/scd.2022.0067","DOIUrl":"https://doi.org/10.1089/scd.2022.0067","url":null,"abstract":"<p><p>Stem cell replacement therapy has emerged as one of the most promising treatment options for retinal degenerative diseases, which are the main causes of irreversible vision loss. Three-dimensional (3D) retinal organoid culture is a cutting-edge technology for differentiating embryonic stem cells into retinal cells by forming a laminated retinal structure. However, 3D culture systems have strict requirements with respect to the experimental environment and culture technologies. Our study aimed to investigate the effect of retinal conditioned medium (RCM) at different developmental stages on the early differentiation of embryonic stem cells into retina in a 3D culture system. In this study, we added RCM to the 3D culture system and found that it could promote the differentiation of mouse embryonic stem cells (mESCs) into neuroretina. We further explored the possible mechanisms of RCM that regulate differentiation through proteomic analysis. RCM at different time points disclosed different protein profiles. Proteins which improved energy metabolism of mESCs might help improve the viability of embryonic bodies. We then screened out <i>Snap25</i>, <i>Cntn1</i>, <i>Negr1</i>, <i>Dpysl2</i>, <i>Dpysl3</i>, and <i>Crmp1</i> as candidate proteins that might play roles in the differentiation and neurogenesis processes of mESCs, hoping to provide a basis for optimizing a retinal differentiation protocol from embryonic stem cells.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10689859","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}