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Review
Obstetrics & Gynecology
Sara Di Persio et al.
Summary: This review provides an overview of the increasing amount of single-cell RNA-sequencing data in the field of human male reproduction. Transcriptional profiles of thousands of testicular cells covering different developmental stages and male infertility have been generated. The review also discusses novel concepts regarding spermatogonial and somatic cell subtypes and their crosstalk, and provides corresponding marker genes for identification. Furthermore, it explores the potential clinical implications of scRNA-seq findings, the need for spatial information, and the necessity to validate results at other regulatory levels.
HUMAN REPRODUCTION
(2023)
Review
Obstetrics & Gynecology
Hamdy Y. Y. Ismail et al.
Summary: Infertility is a serious issue in society, with male factor infertility accounting for 25-50% of cases. Testicular degeneration can be caused by various factors, and stem cells have shown potential in regeneration. Based on previous research and trials, MSCs are considered an effective therapy for testicular degeneration.
REPRODUCTIVE SCIENCES
(2023)
Review
Andrology
Manou Huijben et al.
Summary: Clomiphene citrate is an effective and safe therapy for improving sperm quality in infertile men, as it increases sperm concentration and motility. This systematic review and meta-analysis provides evidence of the efficacy of clomiphene citrate as a treatment for male infertility.
Review
Endocrinology & Metabolism
R. Mazzilli et al.
Summary: This article reviews the impact of the male factor on assisted reproductive technology (ART) and provides an overview of the indications, minimum access criteria, and outcomes of ART techniques in relation to male factor.
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
(2023)
Article
Chemistry, Medicinal
Tracey L. Bonfield et al.
Summary: Human Mesenchymal Stem Cell (hMSC) immunotherapy has shown effectiveness in treating diseases through anti-inflammatory and anti-microbial effects. In the case of cystic fibrosis (CF), hMSC immunotherapy is important for patients with established disease and those with CF mutations not addressed by current treatments. However, the potency of hMSC products varies and further research is needed to predict their efficacy in clinical settings.
Review
Cell Biology
Michael R. Hicks et al.
Summary: Stem cell niches are dynamic microenvironments that support stem cells throughout life. The emerging niche, distinct from the adult niche, is responsible for supporting progenitor cells during organ system development. This review focuses on the skeletal muscle microenvironment and how it influences the formation of emerging niches and satellite cell niches. The regulation of intrinsic properties of progenitor and stem cells by stem cell niches from development to adulthood is discussed, along with the potential applications of generating emerging niches from human pluripotent stem cells for regeneration and therapeutics.
TRENDS IN CELL BIOLOGY
(2023)
Review
Obstetrics & Gynecology
Takahiro Suzuki
Summary: Single-cell RNA sequencing is a powerful tool for studying spermatogenesis, but its technical and bioinformatics requirements make it difficult for many researchers to use. This review provides an overview of experimental and computational methods for single-cell RNA sequencing and summarizes recent discoveries in spermatogenesis obtained through this technique. It highlights the potential of single-cell RNA sequencing in advancing our understanding of spermatogenesis and male fertility therapy.
REPRODUCTIVE MEDICINE AND BIOLOGY
(2023)
Article
Hematology
Antonina Kurtova et al.
Summary: The self-renewal and differentiation of stem and progenitor cells are regulated by systemic and local cues. RSPO3 is important for Wnt signaling and is usually expressed in the stem cell niche to regulate stem cell expansion and differentiation. Disrupting the niche-restricted expression of RSPO3 can affect tissue organization and lead to disorders and cancers.
Review
Cell & Tissue Engineering
Donald G. Phinney et al.
Summary: This article discusses the role of TWIST1 in MSCs and how it can be used to develop MSC therapeutics tailored to specific diseases. Based on evidence from pre-clinical models, MSCs exert therapeutic effects by suppressing inflammation and immune-mediated responses and by changing the polarization state of tissue resident macrophages. The article also highlights the mechanistic link between the stem/progenitor and paracrine functions of MSCs and proposes the development of metrics to predict MSC potency.
Article
Cell & Tissue Engineering
Takako Yamamoto et al.
Summary: This study introduces a novel approach to determine the critical quality attributes (CQAs) of mesenchymal stem cells (MSCs) for immunosuppressive effects. MSCs retained homeostatic replication potentials in early passages but lost them in late passages. The timing of cell harvesting and selection of MSCs with homeostatic features are important for defining CQAs.
STEM CELLS TRANSLATIONAL MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Yoojin Seo et al.
Summary: This review summarizes the application of mesenchymal stem cells (MSCs) and their secretome in the treatment of inflammatory skin diseases, as well as the strategies for engineering cell-free therapeutics through secretome. The direct application of MSCs often fails to produce stable therapeutic outcomes, and the use of MSC-derived paracrine factors, such as secretome and exosomes, offers a promising alternative. Bioengineering techniques and biocompatible materials can also be utilized to improve the delivery efficiency and bioavailability of secretome in vivo.
JOURNAL OF PHARMACEUTICAL INVESTIGATION
(2023)
Review
Endocrinology & Metabolism
Bianca de Oliveira Horvath-Pereira et al.
Summary: Traditional therapies for male infertility focus on restoring fertility or preserving sperm in severe cases, but have limitations that impact their effectiveness. Reproductive medicine has turned to biotechnological alternatives, such as tissue-engineered testicular tissue reconstruction, to improve infertility treatment and gamete preservation. This approach mimics the testicular microenvironment to maintain male gametes in culture or produce viable grafts for transplantation. The use of biomaterials plays a crucial role in these artificial biological systems, but each material has advantages and disadvantages. This review discusses the progress and challenges in testicular regenerative medicine and the reconstruction of the testicular microenvironment using tissue bioengineering approaches.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Cell Biology
Natascha Piede et al.
Summary: A flow cytometry-based mixed lymphocyte reaction (MLR) was developed to analyze the inhibitory effect of MSCs on T cell proliferation. The MLR showed <10% variation for repeatability and <15% for intermediate precision, and a linear correlation of r = 0.9021 compared to a non-compendial reference method. The assay was unaffected by PBMC inter-donor variability, demonstrating its applicability as part of quality control tests for the validation of MSCs as a clinical product.
Article
Chemistry, Physical
Chunxiao Qi et al.
Summary: The study developed size-controllable nanovesicles (Meseomes) mimicking exosomes by utilizing membranes and secretome from potency-enhanced MSCs. Meseomes showed significant enhancement of various cellular effects in vitro compared to traditional cell or exosome therapies, offering a promising alternative for regenerative medicine. In animal models, systemic and local administration of Meseomes led to improved liver function, tissue recovery, and enhanced angiogenesis, showcasing the therapeutic potential of these acellular nanovesicles.
Review
Microbiology
Mahin Izadi et al.
Summary: Some microbial sexually transmitted infections (STIs) can have negative effects on the reproductive tract, sperm function, and male fertility. Chlamydia trachomatis, the most common asymptomatic preventable bacterial STI, can affect sperm and the male reproductive tract. Recent studies have shown that exosomes derived from mesenchymal stem cells (MSCs) have therapeutic effects, improving damaged sperm and treating asthenozoospermia. Therefore, exosomes could be a promising new approach for treating male infertility.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Georgy Sagaradze et al.
Summary: Stem and progenitor cells within stem cell niches are crucial for tissue renewal and regeneration, and dysfunction in these niches could lead to the development of diseases. Male infertility may be associated with disturbances in spermatogonial stem cell niches. Mesenchymal stromal cells and their secretome show potential in recovering injured stem cell niches, but their mechanisms of action remain unclear.
BIOMEDICAL JOURNAL
(2022)
Review
Cell Biology
Giuliana Mannino et al.
Summary: Adult stem cells are essential for tissue homeostasis, growth, and regeneration, residing in specialized environments called niches. Interactions within the niche, including intrinsic factors, supporting cells, extracellular matrix, and signaling pathways, govern cell fate and regulate proliferation and differentiation. Tissues can be classified based on their turnover rate and repair abilities, with stem cell niches playing a crucial role in tissue maintenance and response to injury or disease.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Cell & Tissue Engineering
Yusheng Cai et al.
Summary: Stem cell therapies offer promising approaches for treating various diseases by addressing stem cell exhaustion and dysfunction. Recent advances in understanding the mechanisms of stem cell regeneration and rejuvenation strategies utilizing intrinsic and extrinsic factors may pave the way for interventions to delay aging and treat age-associated diseases.
STEM CELLS TRANSLATIONAL MEDICINE
(2022)
Review
Endocrinology & Metabolism
William W. Wright
Summary: This review focuses on the in vivo regulation of spermatogonial stem cells (SSCs) in adult testes by glial cell line-derived neurotrophic factor (GDNF). Through chemical-genetic approach, the inhibition of GDNF stimulation of SSCs was found to decrease replication and increase differentiation of SSCs, ultimately leading to the loss of all SSCs and resembling the condition of Sertoli cell-only (SCO) syndrome. Abnormally low expression of GDNF, FGF2, and FGF8 was observed in infertile human testes, although some SCO testes still contain SSCs. Restoration of GDNF signaling showed partial rebuilding of depleted SSC pool, suggesting GDNF as a potential therapy for men with SCO syndrome.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cell & Tissue Engineering
Ricardo Malvicini et al.
Summary: This study standardized a quick, cheap, and reproducible in vitro macrophage assay to evaluate and estimate the anti-inflammatory activity of MSC-sEVs.
Article
Multidisciplinary Sciences
Jun Li et al.
Summary: In this study, a hierarchical skin proteome map is constructed to identify and analyze the functions of ECM proteins, revealing TGFBI as a glycoprotein that enhances the growth and function of epidermal stem cells and promotes wound healing.
NATURE COMMUNICATIONS
(2022)
Review
Multidisciplinary Sciences
Donghai Zhang et al.
Summary: Reproductive immunology study explores the role of immunity in reproductive physiology and related diseases, such as ovulation disorders, low-quality sperm production, embryo implantation failure, and pregnancy maintenance disorders. Macrophages play important roles in the reproductive system, including regulating endometrial receptivity, embryo implantation, and spermatogenesis. Macrophages are also associated with diseases such as recurrent implantation failure, unexplained recurrent miscarriage, polycystic ovary syndrome, and endometriosis.
Article
Cell & Tissue Engineering
Ariel Joy Lipat et al.
Summary: This study examined the secretory chemokine responses of mesenchymal stromal cells (MSCs) and developed a multiplex analytical method to evaluate their potency. The researchers found that MSCs' innate ability to secrete chemokines is correlated with their metabolic fitness, and the innate secretion of chemokines has a unique correlation pattern. They also found that the combination of IFN gamma and TNF alpha stimulation produces more robust and broad matrix chemokine responses in MSCs compared to individual stimulations. Additionally, the study identified chemokines that can predict immune suppression in MSC and peripheral blood mononuclear cell coculture analysis.
STEM CELLS TRANSLATIONAL MEDICINE
(2022)
Article
Immunology
Max A. Skibber et al.
Summary: Mechanotransduction, achieved by exposing MSC to various grades of wall shear stress (WSS), enhances their immunomodulatory potential independent of classical pro-inflammatory cytokines. The study suggests biomechanical conditioning as a viable and scalable pre-conditioning alternative to enhance the immunomodulatory capacity of MSC in cell therapy manufacturing.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Pauline Po Yee Lui et al.
Summary: This review discusses the general and tissue-specific considerations for manufacturing MSC-EVs for clinical translation in the treatment of tendon and ligament injuries, including GMP-compliant manufacturing and quality control, safety and efficacy issues, and compatibility with arthroscopy.
Article
Cell & Tissue Engineering
Cassia Lisboa Braga et al.
Summary: Hypoxia preconditioning can enhance the survival and metabolic activity of bone marrow-derived MSCs and increase the release of EVs. The proteomics profile of MSCs and EVs under hypoxic conditions is associated with pathways and biological processes related to glycolysis, the immune system, and extracellular matrix organization.
Article
Biochemistry & Molecular Biology
Anna Monakova et al.
Summary: Idiopathic male infertility is a common issue in developed countries with no specific treatment options. The use of mesenchymal stromal cells (MSCs) and their secretome may be a promising approach to restore male fertility. This study suggests a novel method to evaluate the potency of MSC secretome for idiopathic male infertility treatment by analyzing testosterone production by Leydig cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Kekoolani S. Visan et al.
Summary: sEVs, important for cancer diagnostics and therapeutics, can be isolated using both ultracentrifugation and tangential flow filtration methods. While both methods yield consistent sEV populations with similar size distributions, tangential flow filtration produces significantly higher yields, making it more suitable for large-scale research applications.
JOURNAL OF EXTRACELLULAR VESICLES
(2022)
Review
Medicine, General & Internal
Ashok Agarwal et al.
Summary: Infertility affects 8-12% of couples globally, with male factors contributing to around 50%. The causes of male infertility are diverse, requiring thorough evaluation to identify treatable or reversible factors. Semen analysis is key for evaluation, while advanced tests have been developed to investigate sperm quality and function.
Review
Oncology
Tian Zhou et al.
Summary: MSC therapy for clinical applications faces challenges due to inconsistent criteria for MSCs identity and their inherited heterogeneity. Strategies have been developed to overcome these challenges with the emergence of advanced biological techniques and substantial improvements in bio-engineered materials.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Mara Martin-Alonso et al.
Summary: Smooth muscle cells in the intestine may play a crucial role in supplying BMP antagonists, maintaining reparative and fetal-like features, and influencing intestinal epithelial regeneration through MMP17. This discovery establishes smooth muscle cells as modulators of intestinal epithelial regeneration and the stem cell niche.
NATURE COMMUNICATIONS
(2021)
Article
Cell & Tissue Engineering
Yang Wang et al.
Summary: This study reviewed the safety of mesenchymal stem cell (MSC) therapy in different populations with different diseases, showing no serious adverse events and only minor adverse reactions such as transient fever, constipation, fatigue, and sleeplessness. Overall, MSC administration was found to be safe compared to other placebo modalities.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Cell & Tissue Engineering
Mario Gimona et al.
Summary: Mesenchymal stromal/stem cells (MSCs) have been approved for treating certain diseases through paracrine secretion of small extracellular vesicles (sEVs). Despite the potential advantages of sEV preparations over cellular MSC products, there are challenges in developing MSC-sEV drug products, including establishing quality control metrics and developing effective potency assays.
Article
Andrology
Yi-Ting Cai et al.
Summary: The study demonstrated that the treatment with bone marrow-derived mesenchymal stem cell secretion significantly improved spermatogenesis in mice with azoospermia induced by busulfan, by promoting Sertoli cell adhesion integrity.
Review
Pharmacology & Pharmacy
Muhammad Nabeel Shahid et al.
Summary: This review investigated the efficacy of various pharmacological interventions for male infertility, showing that all interventions had a significantly positive effect on male infertility.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Michela Mocchi et al.
Summary: This study aimed to optimize the production process of mesenchymal stem cell-derived secretome, lyosecretome, by investigating sources of variability and modifying the manufacturing process. Different excipient ratios did not significantly affect the product quality, but increasing the total concentration of excipients improved the preservation of proteins and lipids. By concentrating the final product to achieve a specific protein concentration, the manufacturing process was standardized, resulting in a more reproducible composition and higher biological activity of the product.
Article
Cell Biology
Sara Di Persio et al.
Summary: The study revealed significant alterations in the spermatogonial compartment of crypto male infertility patients, with changes in chromatin structure and fewer reserve stem cells. The regulatory mechanisms involving EGR4 and its transcriptional repressor UTF1 are identified as key factors affecting the genetic integrity of germline cells in crypto patients.
CELL REPORTS MEDICINE
(2021)
Article
Cell & Tissue Engineering
Chiara Giannasi et al.
Summary: The study evaluated the characteristics of 3 CM samples from adipose-derived MSCs, including size and distribution of EVs, protein and lipid concentrations, demonstrating high homogeneity among samples suitable for EV retention and concentration. The study identified key ingredients and consistent levels in the ASC-CM samples, which may represent a promising quality control for clinical applications.
STEM CELLS INTERNATIONAL
(2021)
Review
Cell Biology
Wei-Zhan Zhuang et al.
Summary: Mesenchymal stem/stromal cells (MSCs) are a promising resource for cell-based therapy due to their high immunomodulation ability and tropism towards inflamed and injured tissues. However, the lack of standardized methods to evaluate the safety, efficacy, and biodistribution of MSCs has been a major hindrance to their clinical application.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Review
Andrology
Tejas Gundewar et al.
Summary: Clomiphene has been used to manage male sub-fertility since 1967, but studies have shown that it may lead to a decline in sperm parameters, which in some cases are irreversible. More research is needed to understand the full extent of this effect.
Review
Andrology
E. Oliver et al.
Review
Cell Biology
Jing Liu et al.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Review
Cell & Tissue Engineering
Elani F. Wiest et al.
Review
Multidisciplinary Sciences
Oren Levy et al.
Article
Cell Biology
Michael J. Borrett et al.
Review
Cell Biology
Georgy D. Sagaradze et al.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Review
Urology & Nephrology
Daniel Z. Sun et al.
NATURE REVIEWS UROLOGY
(2019)
Review
Pharmacology & Pharmacy
Rossella Cannarella et al.
EXPERT OPINION ON PHARMACOTHERAPY
(2019)
Article
Cell & Tissue Engineering
Raghavan Chinnadurai et al.
Article
Biochemistry & Molecular Biology
Gregorio Carballo-Uicab et al.
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Cell & Tissue Engineering
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STEM CELL RESEARCH & THERAPY
(2019)
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Medicine, Research & Experimental
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BIOMEDICINE & PHARMACOTHERAPY
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Cell & Tissue Engineering
Mark F. Pittenger et al.
NPJ REGENERATIVE MEDICINE
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Developmental Biology
Manju Sharma et al.
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Cell Biology
Shosei Yoshida
DEVELOPMENT GROWTH & DIFFERENTIATION
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Cell & Tissue Engineering
Natalia Kalinina et al.
STEM CELL RESEARCH & THERAPY
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Cell Biology
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NATURE REVIEWS MOLECULAR CELL BIOLOGY
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