Pub Date : 2026-01-23DOI: 10.1007/s12015-025-11041-0
Muhammad Iqbal Qureshi, Afsar Ali Mian, Irfan Khan
Regenerative medicine promises the possibility of custom-made, ready-to-use human organs without the risk of immune rejection. Human pluripotent stem cells (hPSCs) are the workhorses of stem cell-based tissue engineering. With inherent capabilities to adopt nearly any cellular form, they are supposed to solve the soaring demand for transplantable organs. Technically, PSCs are converted into cells of interest using a stepwise approach (differentiation) mimicking embryonic development. Animal models have been crucial in advancing our understanding of human embryology, mainly due to the widespread conservation of the mammalian regulome. Differentiation protocols have evolved with time from two-dimensional (2D) monocultures, which are relatively easy to maintain, to more complex three-dimensional (3D) organoids that enhance the capacity for staging multilineage assemblies. The appeal of 3D systems lies in their operational resemblance to the actual morphology of tissues. While each platform has pros and cons, its specific strengths can be leveraged to tell a more compelling story of development and how complex pathologies take root. Here, we reviewed key methodologies for the in vitro production of human functional cell lineages from hPSCs. We have connected the most recent science to the work that came before and analyzed where the trends we see now might lead. We examined the shift from 2D cell monolayers to 3D organoids. Additionally, we highlighted hybrid approaches and innovative discoveries that support the reliable generation of physiologically mature cells, enabling the study of development and disease at new depths.
{"title":"Advances in Internal Organogenesis: Differentiation and Morphogenesis of Human Ventral Cavity Organs.","authors":"Muhammad Iqbal Qureshi, Afsar Ali Mian, Irfan Khan","doi":"10.1007/s12015-025-11041-0","DOIUrl":"https://doi.org/10.1007/s12015-025-11041-0","url":null,"abstract":"<p><p>Regenerative medicine promises the possibility of custom-made, ready-to-use human organs without the risk of immune rejection. Human pluripotent stem cells (hPSCs) are the workhorses of stem cell-based tissue engineering. With inherent capabilities to adopt nearly any cellular form, they are supposed to solve the soaring demand for transplantable organs. Technically, PSCs are converted into cells of interest using a stepwise approach (differentiation) mimicking embryonic development. Animal models have been crucial in advancing our understanding of human embryology, mainly due to the widespread conservation of the mammalian regulome. Differentiation protocols have evolved with time from two-dimensional (2D) monocultures, which are relatively easy to maintain, to more complex three-dimensional (3D) organoids that enhance the capacity for staging multilineage assemblies. The appeal of 3D systems lies in their operational resemblance to the actual morphology of tissues. While each platform has pros and cons, its specific strengths can be leveraged to tell a more compelling story of development and how complex pathologies take root. Here, we reviewed key methodologies for the in vitro production of human functional cell lineages from hPSCs. We have connected the most recent science to the work that came before and analyzed where the trends we see now might lead. We examined the shift from 2D cell monolayers to 3D organoids. Additionally, we highlighted hybrid approaches and innovative discoveries that support the reliable generation of physiologically mature cells, enabling the study of development and disease at new depths.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146041789","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}
Pub Date : 2026-01-20DOI: 10.1007/s12015-026-11063-2
Yueqiu Chen, Han Shen, Zhenya Shen
{"title":"Ferroptosis: A Novel Therapeutic Target for Cardiovascular Diseases.","authors":"Yueqiu Chen, Han Shen, Zhenya Shen","doi":"10.1007/s12015-026-11063-2","DOIUrl":"https://doi.org/10.1007/s12015-026-11063-2","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012397","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}
Estrogen deficiency-induced uterine atrophy is a major cause of menstrual disorders and infertility in postmenopausal women and patients with premature ovarian failure. However, current hormone replacement therapies carry long-term risks and fail to achieve physiological endometrial regeneration. It has been demonstrated that dimethyloxalylglycine (DMOG) can augment the therapeutic effects of mesenchymal stem cells (MSCs), but the effects of DMOG-pretreated MSCs on Estrogen deficiency-induced uterine atrophy remain unclear. This study aimed to explore whether DMOG-pretreated human umbilical cord MSCs (hUC-MSCs) could repair estrogen deficiency-induced uterine atrophy. The results showed that compared with the MSCs group, the DM group significantly improved the disordered estrous cycle of ovariectomy (OVX) mice, increased serum estradiol (E2) levels, and restored uterine morphology and index, and facilitated the recovery of endometrial thickness and gland number. Masson staining confirmed that the DM group had a more significant reduction in endometrial fibrosis. Immunofluorescence demonstrated enhanced expression of Oct-4 and Nanog in the DM group, which suggests that DMOG-pretreated hUC-MSCs may exert paracrine effects to promote the formation of VSELs, thereby facilitating the remodeling of endometrial epithelial structure. This provides a novel and effective strategy for the treatment of estrogen deficiency-related uterine atrophy.
{"title":"DMOG Enhances hUC-MSCs Paracrine Activity to Promote Endometrial Epithelial Cells Reconstitution Via VSELs Formation in Ovariectomized Mice.","authors":"Anfeng Ning, Nansong Xiao, Zi Chen, Xiaoqin Yu, Chunyi Guan, Xu Ma, Hongfei Xia","doi":"10.1007/s12015-026-11058-z","DOIUrl":"https://doi.org/10.1007/s12015-026-11058-z","url":null,"abstract":"<p><p>Estrogen deficiency-induced uterine atrophy is a major cause of menstrual disorders and infertility in postmenopausal women and patients with premature ovarian failure. However, current hormone replacement therapies carry long-term risks and fail to achieve physiological endometrial regeneration. It has been demonstrated that dimethyloxalylglycine (DMOG) can augment the therapeutic effects of mesenchymal stem cells (MSCs), but the effects of DMOG-pretreated MSCs on Estrogen deficiency-induced uterine atrophy remain unclear. This study aimed to explore whether DMOG-pretreated human umbilical cord MSCs (hUC-MSCs) could repair estrogen deficiency-induced uterine atrophy. The results showed that compared with the MSCs group, the DM group significantly improved the disordered estrous cycle of ovariectomy (OVX) mice, increased serum estradiol (E2) levels, and restored uterine morphology and index, and facilitated the recovery of endometrial thickness and gland number. Masson staining confirmed that the DM group had a more significant reduction in endometrial fibrosis. Immunofluorescence demonstrated enhanced expression of Oct-4 and Nanog in the DM group, which suggests that DMOG-pretreated hUC-MSCs may exert paracrine effects to promote the formation of VSELs, thereby facilitating the remodeling of endometrial epithelial structure. This provides a novel and effective strategy for the treatment of estrogen deficiency-related uterine atrophy.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967103","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}
The effective repair of tendon injuries represents a significant challenge in the selection of an appropriate regeneration strategy. Meanwhile, umbilical cord-derived mesenchymal stem cells (UC-MSCs) have been employed in the treatment of a range of diseases due to a number of advantageous characteristics, including low immunogenicity, high proliferation and differentiation potential, extensive availability, ease of large-scale production, absence of ethical constraints, and immunomodulatory functions. It has demonstrated considerable clinical application potential and offer a promising avenue for the treatment of tendon injuries. The core strategies may be broadly classified into three categories: direct stem cell injection, transplantation of biological scaffolds with tissue engineering technology, and the use of stem cell-derived products. This review will provide an in-depth analysis of the pathophysiological mechanisms of tendon repair, describe the unique properties of UC-MSCs, and systematically evaluate the advantages and limitations of these treatment strategies, aiming to provide a solid theoretical basis and scientific guidance for the biological research and clinical application of UC-MSCs in the field of tendon repair. The translational potential of this article: Given the low immunogenicity, good biosafety, and strong differentiation potential possessed by UC-MSCs, it is expected to provide a both safe and effective therapeutic option for tendon injuries through certain processing measures, such as combining UC-MSCs with biomaterials or extracting their products. In addition, the extraction process of UC-MSCs is simple and non-invasive, which makes it easy to realize clinical mass production. Therefore, the use of UC-MSCs for tendon repair is significant for clinical translation of tendon injury treatment.
{"title":"Human Umbilical Cord-Derived Mesenchymal Stem Cells-Involved Strategies: Advancing Tendon Injuries Therapy Towards Clinical Translation.","authors":"Mumin Cao, Mengze Tong, Yunmeng Pu, Xuepeng Lv, Yimin Sun, Haoyu Zhang, Renwang Sheng, Hao Wang, Yucheng Gao, Guangchun Dai, Fei Xiong, Qianqian Wang, Yunfeng Rui","doi":"10.1007/s12015-025-11054-9","DOIUrl":"https://doi.org/10.1007/s12015-025-11054-9","url":null,"abstract":"<p><p>The effective repair of tendon injuries represents a significant challenge in the selection of an appropriate regeneration strategy. Meanwhile, umbilical cord-derived mesenchymal stem cells (UC-MSCs) have been employed in the treatment of a range of diseases due to a number of advantageous characteristics, including low immunogenicity, high proliferation and differentiation potential, extensive availability, ease of large-scale production, absence of ethical constraints, and immunomodulatory functions. It has demonstrated considerable clinical application potential and offer a promising avenue for the treatment of tendon injuries. The core strategies may be broadly classified into three categories: direct stem cell injection, transplantation of biological scaffolds with tissue engineering technology, and the use of stem cell-derived products. This review will provide an in-depth analysis of the pathophysiological mechanisms of tendon repair, describe the unique properties of UC-MSCs, and systematically evaluate the advantages and limitations of these treatment strategies, aiming to provide a solid theoretical basis and scientific guidance for the biological research and clinical application of UC-MSCs in the field of tendon repair. The translational potential of this article: Given the low immunogenicity, good biosafety, and strong differentiation potential possessed by UC-MSCs, it is expected to provide a both safe and effective therapeutic option for tendon injuries through certain processing measures, such as combining UC-MSCs with biomaterials or extracting their products. In addition, the extraction process of UC-MSCs is simple and non-invasive, which makes it easy to realize clinical mass production. Therefore, the use of UC-MSCs for tendon repair is significant for clinical translation of tendon injury treatment.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145960278","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}
Pub Date : 2026-01-10DOI: 10.1007/s12015-026-11056-1
Büşra Şensoy Gün
{"title":"Hair Graying as an Evolutionary Checkpoint against Malignancy: a Stem Cell Perspective.","authors":"Büşra Şensoy Gün","doi":"10.1007/s12015-026-11056-1","DOIUrl":"https://doi.org/10.1007/s12015-026-11056-1","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949179","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}
Pub Date : 2026-01-07DOI: 10.1007/s12015-025-11048-7
Pascal Eber, Ana M P Baggio, Yannick M Sillmann, Philippe Korn, David A Keith, Shruti Handa, Fernando P S Guastaldi
Background: Despite affecting approximately 30% of the population, the pathogenesis of temporomandibular disorders (TMD) remains poorly understood. Conditions such as disc displacement and joint degeneration are often associated with biomechanical dysfunction. Identifying and categorizing biomarkers in the articular disc may enhance our understanding of disease mechanisms and progression, potentially improving diagnostic accuracy and therapeutic outcomes.
Aim: This review examines patterns among immunohistochemical biomarkers in the articular disc, with a focus on internal derangement and disc displacement. It also explores associations with clinical, radiological, and histological findings, defining the functional and stage-specific relevance of each marker.
Methods: A systematic search of major databases and journals identified studies that used immunohistochemical methods and included control groups. Biomarker patterns were analyzed in isolation and in relation to clinical, radiological, and histological findings. Patient demographics were examined to determine their alignment with disease trends. Study selection followed PRISMA guidelines; bias was assessed using the Newcastle-Ottawa Scale.
Results: The review included 511 patients (579 samples) and 132 controls (158 samples). Analysis identified 24 biomarkers, providing valuable insights into their role in inflammatory progression, ECM remodeling, and tissue degeneration. Biomarkers were classified according to functional and stage-specific patterns, facilitating early detection, refining disease staging, and supporting individualized treatment strategies.
Conclusion: Disc biopsy offers unique insights into the joint- and disc-specific mechanisms that drive TMD progression from disc displacement to degenerative findings. However, its clinical use remains limited by its invasive nature, ethical constraints, and the lack of standardized protocols for reliable study design and validated biomarker profiles.
{"title":"Decoding Temporomandibular Disorders: Identifying Stage-Specific and Functional Patterns in the Articular Disc.","authors":"Pascal Eber, Ana M P Baggio, Yannick M Sillmann, Philippe Korn, David A Keith, Shruti Handa, Fernando P S Guastaldi","doi":"10.1007/s12015-025-11048-7","DOIUrl":"https://doi.org/10.1007/s12015-025-11048-7","url":null,"abstract":"<p><strong>Background: </strong>Despite affecting approximately 30% of the population, the pathogenesis of temporomandibular disorders (TMD) remains poorly understood. Conditions such as disc displacement and joint degeneration are often associated with biomechanical dysfunction. Identifying and categorizing biomarkers in the articular disc may enhance our understanding of disease mechanisms and progression, potentially improving diagnostic accuracy and therapeutic outcomes.</p><p><strong>Aim: </strong>This review examines patterns among immunohistochemical biomarkers in the articular disc, with a focus on internal derangement and disc displacement. It also explores associations with clinical, radiological, and histological findings, defining the functional and stage-specific relevance of each marker.</p><p><strong>Methods: </strong>A systematic search of major databases and journals identified studies that used immunohistochemical methods and included control groups. Biomarker patterns were analyzed in isolation and in relation to clinical, radiological, and histological findings. Patient demographics were examined to determine their alignment with disease trends. Study selection followed PRISMA guidelines; bias was assessed using the Newcastle-Ottawa Scale.</p><p><strong>Results: </strong>The review included 511 patients (579 samples) and 132 controls (158 samples). Analysis identified 24 biomarkers, providing valuable insights into their role in inflammatory progression, ECM remodeling, and tissue degeneration. Biomarkers were classified according to functional and stage-specific patterns, facilitating early detection, refining disease staging, and supporting individualized treatment strategies.</p><p><strong>Conclusion: </strong>Disc biopsy offers unique insights into the joint- and disc-specific mechanisms that drive TMD progression from disc displacement to degenerative findings. However, its clinical use remains limited by its invasive nature, ethical constraints, and the lack of standardized protocols for reliable study design and validated biomarker profiles.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913189","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}