Онтогенез, Journal Year: 2023, Volume and Issue: 54(5), P. 306 - 322
Published: Sept. 1, 2023
Language: Английский
Development, Journal Year: 2023, Volume and Issue: 150(11)
Published: June 1, 2023
ABSTRACT Recent years have seen exciting progress across human embryo research, including new methods for culturing embryos, transcriptional profiling of embryogenesis and gastrulation, mapping lineage trajectories, experimenting on stem cell-based models. These advances are beginning to define the dynamical principles development stages, tissues organs, enabling a better understanding before birth in health disease, potentially leading improved treatments infertility developmental disorders. However, there still significant roadblocks en route this goal. Here, we highlight technical challenges studying early propose ways means overcome some these constraints.
Language: Английский
Citations
25
Cell, Journal Year: 2024, Volume and Issue: 187(23), P. 6566 - 6583.e22
Published: Sept. 26, 2024
Many mammals can temporally uncouple conception from parturition by pacing down their development around the blastocyst stage. In mice, this dormant state is achieved decreasing activity of growth-regulating mTOR signaling pathway. It unknown whether ability conserved in general and humans particular. Here, we show that pathway induces human pluripotent stem cells (hPSCs) blastoids to enter a with limited proliferation, developmental progression, capacity attach endometrial cells. These vitro assays that, similar other species, dormancy active stage reversible at both functional molecular levels. The has potential implications for reproductive therapies.
Language: Английский
Citations
8
Human Reproduction, Journal Year: 2023, Volume and Issue: 38(8), P. 1449 - 1463
Published: April 29, 2023
Abstract Research focused on human reproductive biology has primarily relied upon clinical samples affording mainly descriptive studies with limited implementation of functional or mechanistic understanding. More importantly, restricted access to embryonic material necessitated the use animals, rats and mice, short-term primary cell cultures derived from patient material. While developmental processes are generally conserved across mammals, specific features unique reproduction have resulted in development human-based vitro systems designed retain recapitulate key molecular cellular important humans. Of note, major advances 3D epithelial stem cell-based modeling organ been made. These cultures, broadly referred as organoids, enable research aimed at understanding hierarchies controlling differentiation function. Moreover, organoids allow pre-clinical testing pharmacological substances, both safety efficacy standpoints, hold large potential driving aspects personalized medicine that were previously not possible traditional models. In this mini-review, we focus summarizing current state regenerative organoid culture female male tracts model development, maintenance, Specifically, will introduce models ovary/fallopian tube, endometrium, cervix, prostate gland, testes. We also describe pre-implanting blastocyst trophoblast, its extraembryonic trophectoderm central fetal, maternal, overall pregnancy health. foundational leading their outline utility well limitations common many these platforms.
Language: Английский
Citations
16
Journal of Cellular Physiology, Journal Year: 2024, Volume and Issue: 239(4)
Published: Jan. 14, 2024
Abstract Transplantation of brown adipose tissue (BAT) is a promising approach for treating obesity and metabolic disorders. However, obtaining sufficient amounts functional BAT or adipocytes transplantation remains major challenge. In this study, we developed hydrogel that combining acellular matrix (AAM) GelMA HAMA can be adjusted stiffness by modulating the duration light‐crosslinking. We used human white tissue‐derived microvascular fragments to create beige organoids (BAO) were encapsulated in either soft stiff AAM hydrogel. found BAOs cultivated hydrogels with high demonstrated increased activity upregulation thermogenesis‐related genes. When transplanted into obese type 2 diabetes mice, HFD + BAO group showed sustained improvements rate, resulting significant weight loss decreased blood glucose levels. Furthermore, mice marked reduction nonalcoholic liver steatosis, indicating improved function. contrast, 2D‐cultured failed produce these beneficial effects. Our findings demonstrate feasibility fabricating vitro administering them injection, which may represent therapeutic diabetes.
Language: Английский
Citations
6
Cell stem cell, Journal Year: 2024, Volume and Issue: 31(10), P. 1398 - 1418
Published: Oct. 1, 2024
Language: Английский
Citations
6
Acta Obstetricia Et Gynecologica Scandinavica, Journal Year: 2024, Volume and Issue: 104(2), P. 258 - 266
Published: Dec. 18, 2024
Increasing infertility rates represent a growing medical challenge in modern societies resulting from complex interplay of sociocultural trends, lifestyle factors, exposure to environmental toxins, and underlying health problems. Women's fertility is particularly vulnerable these shifts. The obesogenic not only accelerates weight gain, but also disrupts ovulation driving the rise infertility. Among several medications used for treating obesity type 2 diabetes, glucagon-like peptide-1 receptor agonists (GLP-1RAs) show promising improvement female most likely by stimulating ovulation. However, effects GLP-1RAs on endometrium remain unclear. Further studies are needed investigate impact endometrial receptivity embryo implantation early development. aim this study address knowledge gap regarding human reproduction, with special focus endometrium. Understanding mechanisms may help develop new strategies improving treatment, reduce failure potential safety concerns teratogenicity adverse developmental outcomes children born women conceiving during or soon after GLP-1RA treatment.
Language: Английский
Citations
5
FEBS Open Bio, Journal Year: 2025, Volume and Issue: unknown
Published: April 19, 2025
Modelling peri‐implantation mammalian development using the self‐organising properties of stem cells is a rapidly growing field that has advanced our understanding cell fate decisions occurring in early embryo. Matrigel, basement membrane matrix, critical substrate used various protocols for its efficacy promoting growth and self‐organisation. However, role driving lineage commitment, whether this effect driven by biochemical or physical cues, not currently clear. Here, we grow embryoid bodies suspension, Matrigel agarose, an inert polysaccharide, to attempt decouple roles better understand how it drives differentiation. We use combination light microscopy, quantitative PCR immunostaining investigate gene protein changes different culture conditions. show aggregates are hindered their ability elongate compared with those grown agarose indicating prohibitive Aggregates also differentiate into endoderm, ectoderm differentiation inhibited. Furthermore, these effects due presence as same witnessed agarose. Our results thus indicate significant complex on morphology bodies.
Language: Английский
Citations
0
Reproductive Toxicology, Journal Year: 2024, Volume and Issue: 125, P. 108558 - 108558
Published: Feb. 15, 2024
Language: Английский
Citations
2
Biology Open, Journal Year: 2023, Volume and Issue: 12(9)
Published: Aug. 25, 2023
ABSTRACT Stem-cell-based embryo models have allowed greater insight into peri-implantation mammalian developmental events that are otherwise difficult to manipulate due the inaccessibility of early embryo. The rapid development this field has resulted in precise roles frequently used supplements such as N2, B27 and Chiron driving stem cell lineage commitment not being clearly defined. Here, we investigate effects these on embryoid bodies better understand their differentiation. We show Wnt signalling a general posteriorising effect aggregates directs differentiation towards mesoderm, confirmed through upregulation posterior mesodermal markers. N2 can mitigate upregulate expression anterior To control gradient subsequent versus fate, make use BMP4 centre conditions express cephalic These findings indicate there is an intricate balance between various culture ability guide models.
Language: Английский
Citations
4
Medical Review, Journal Year: 2024, Volume and Issue: 4(2), P. 90 - 109
Published: March 7, 2024
Pluripotent stem cells (PSCs), characterized by self-renewal and capacity of differentiating into three germ layers, are the programmable building blocks life. PSC-derived multicellular systems, particularly organoids, exhibit great potential for regenerative medicine. However, this field is still in its infancy, partly due to limited strategies robustly precisely control cell behaviors, which tightly regulated inner gene regulatory networks response stimuli from extracellular environment. Synthetic receptors genetic circuits powerful tools customize cellular sense-and-response process, suggesting their underlying roles precise fate decision function reconstruction. Herein, we review progress challenges needed be overcome fields PSC-based therapy system generation, respectively. Furthermore, summarize several well-established synthetic biology applications PSC engineering. Finally, highlight perspectives harnessing engineering
Language: Английский
Citations
1