Cells Tissues Organs最新文献

Migrating cells in tissues are often known to exhibit collective swirling movements. In this paper, we develop an active vertex model with polarity dynamics based on contact inhibition of locomotion (CIL). We show that under this dynamics, the cells form steady-state vortices in velocity, polarity, and cell stress with length scales that depend on polarity alignment rate (ζ), self-motility (v0), and cell-cell bond tension (λ). When the ratio λ/v0 becomes larger, the tissue reaches a near jamming state because of the inability of the cells to exchange their neighbors, and the length scale associated with tissue kinematics increases. A deeper examination of this jammed state provides insights into the mechanism of sustained swirl formation under CIL rule that is governed by the feedback between cell polarities and deformations. To gain additional understanding of how active forcing governed by CIL dynamics leads to large-scale tissue dynamics, we systematically coarse-grain cell stress, polarity, and motility and show that the tissue remains polar even on larger length scales. Overall, we explore the origin of swirling patterns during collective cell migration and obtain a connection between cell-level dynamics and large-scale cellular flow patterns observed in epithelial monolayers.

Momordica charantia (MC) is a traditional plant widely used since ancient times for wound healing. This study evaluated its potential effects on tendon healing. Adult male Wistar albino rats (n = 32, 8 rats in each group) were anesthetized, and their Achilles tendons were prepared for surgical procedures. Group 1 (Cont = control group) was not subjected to any surgery and was used as a control group for baseline values. Group 2 (PR = primary repair group) underwent primary repair (PR) with a monofilament suture after a full-thickness incision of the Achilles tendon. A full-thickness incision was also made to the Achilles tendon of group 3 (CT = collagen tube-administered group), followed by PR and collagen tube insertion. In group 4 (MC = M. charantia-administered group), 1 mL of MC extract was applied locally on the collagen tube in addition to the surgical procedure applied to group 3. The Achilles tendons were excised on the postoperative 40th day and examined stereologically, histologically, and bioinformatically. Data showed that the total volume of the collagen fibers was higher in MC and CT groups than in the PR group. The total volume of the tendon was decreased in MC and CT groups than in the Cont group. The ratios between the volumes of the collagen fibers and total tendon in the MC and CT groups were significantly different from PR, but not different from the Cont group. Additionally, MC improved tenoblastic activity, collagen production, and neovascularization. Bioinformatic interactions showed that the proteases of MC could trigger the signals playing a role on vasculogenesis, reducing inflammation, and contributing to tenoblast activation and collagen remodeling. MC extract ameliorates the healing of injured tendon and can provide satisfactory tendon repair. Further works are recommended to explore the healing capacity of MC.

Introduction: The decellularized extracellular matrix (dECM) from ovarian tissue could be the best scaffold for the development of a transplantable artificial ovary. Typically, dECM from ovarian tissue has been obtained using sodium dodecyl sulfate (SDS), at a concentration of 1% for 24 h. However, SDS can leave residues in the tissue, which may be toxic to the seeded cells. This study aimed to obtain dECM from bovine ovarian tissue using SDS and NaOH at a minimum concentration in the shortest incubation time.

Methods: The respective SDS and NaOH concentrations investigated were 1% and 0.2 m; 0.5% and 0.1 m; 0.1% and 0.02 m; and 0.05% and 0.01 m, with 24-, 12-, and 6-h incubation periods. After the incubation time, the tissue was washed in 50 mL of distilled water for 6 h.

Results: Histological analysis confirmed decellularization and showed the conservation of collagen fibers in all samples following treatment. Furthermore, the lowest SDS and NaOH concentrations that showed no DNA remaining during electrophoresis analysis were 0.1% and 0.02 m when incubated for 24 and 12 h. DNA quantification resulted in <0.2 ng DNA/mg ovarian tissue using these protocols. Additionally, the coculture of dECM (obtained by 0.1% SDS and 0.02 m NaOH for 12 h) with ovarian cells showed that there was no toxic effect for the cells for up to 72 h.

Conclusion: The protocol involving 0.1% SDS and 0.02 m NaOH for 12-h incubation decellularizes bovine ovarian tissue, generating a dECM that preserves the native ECM morphology and is nontoxic to ovarian cells.

Background: With the elderly population projected to double by 2050, there is an urgent need to address the increasing prevalence of age-related debilitating diseases and ultimately minimize discrepancies between the rising lifespan and stagnant health span. Cellular reprogramming by overexpression of Oct3/4, Klf4, Sox2, and cMyc (OKSM) transcription factors is gaining attention in this context thanks to demonstrated rejuvenating effects in human cell cultures and live mice, many of which can be uncoupled from dedifferentiation and loss of cell identity.

Summary: Here, we review current evidence of the impact of cell reprogramming on established aging hallmarks and the underlying mechanisms that mediate these effects. We also provide a critical assessment of the challenges in translating these findings and, overall, cell reprogramming technologies into clinically translatable antiaging interventions.

Key messages: Cellular reprogramming has the potential to reverse at least partially some key hallmarks of aging. However, further research is necessary to determine the biological significance and duration of such changes and to ensure the safety of cell reprogramming as a rejuvenation approach. With this review, we hope to stimulate new research directions in the quest to extend health span effectively.

In our series of studies, the changes in the skin characteristics of mice caused by aging were investigated in correlation with the stem cells for keratinocytes and melanocytes in the natural hair cycle until middle age. The aim of the present review was to investigate these characteristics of hair follicles (HFs) at older age and complete the analysis of these changes as a study throughout the mouse lifetime. In addition, stem cells for keratinocytes and melanocytes were evaluated for changes in skin characteristics caused by aging. Postnatal day 200 (P200) appears to be the age of complete maturation of skin and the onset of aging with regard to HFs. Keratin 15-positive keratinocyte stem cells complete their localization as a quantitatively sufficient amount of progenitor in the hair bulge region and orchestrate the regeneration of hairs in every anagen phase thereafter. Although their frequency is low, an unusual structure of HFs, curved HFs, appear for the first time at P200. Thereafter, abnormal hair curvature continues to increase throughout life. In contrast, HF characteristics derived from melanocytes begin to show a high frequency of hypopigmented hair bulbs at P200 and appear to lead to a significant increase in the number of white hairs. Curved HFs and white hairs were considered biomarkers of aging in mice. The number of tyrosinase-related protein 2-positive melanocyte stem cells in the hair bulge is extremely low and may be one cause underlying not only the induction of melanocyte-derived characteristics by aging but possibly also that of keratinocyte-derived characteristics. These results provide insight into the mechanisms of the actions of stem cells on hair regeneration through the aging process.

Background: Recapitulating mammalian cell type differentiation in vitro promises to improve our understanding of how these processes happen in vivo, while bringing additional prospects for biomedical applications. The establishment of stem cell-derived embryo models and embryonic organoids, which have experienced explosive growth over the last few years, opens new avenues for research due to their scale, reproducibility, and accessibility. Embryo models mimic various developmental stages, exhibit different degrees of complexity, and can be established across species. Since embryo models exhibit multiple lineages organized spatially and temporally, they are likely to provide cellular niches that, to some degree, recapitulate the embryonic setting and enable "co-development" between cell types and neighbouring populations. One example where this is already apparent is in the case of primordial germ cell-like cells (PGCLCs).

Summary: While directed differentiation protocols enable the efficient generation of high PGCLC numbers, embryo models provide an attractive alternative as they enable the study of interactions of PGCLCs with neighbouring cells, alongside the regulatory molecular and biophysical mechanisms of PGC competency. Additionally, some embryo models can recapitulate post-specification stages of PGC development (including migration or gametogenesis), mimicking the inductive signals pushing PGCLCs to mature and differentiate and enabling the study of PGCLC development across stages. Therefore, in vitro models may allow us to address questions of cell type differentiation, and PGC development specifically, that have hitherto been out of reach with existing systems.

Key message: This review evaluates the current advances in stem cell-based embryo models, with a focus on their potential to model cell type-specific differentiation in general and in particular to address open questions in PGC development and gametogenesis.

Background: Marrow stimulation is a common reparative approach to treat injuries to cartilage and other soft tissues (e.g., rotator cuff). It involves the recruitment of bone marrow elements and mesenchymal stem cells (MSCs) into the defect, theoretically initiating a regenerative process. However, the resulting repair tissue is often weak and susceptible to deterioration with time. The populations of cells at the marrow stimulation site (beyond MSCs), and their contribution to inflammation, vascularity, and fibrosis, may play a role in quality of the repair tissue.

Summary: In this review, we accomplish three goals: (1) systematically review clinical trials on the augmentation of marrow stimulation and evaluate their assumptions on the biological elements recruited; (2) detail the cellular populations in bone marrow and their impact on healing; and (3) highlight emerging technologies and approaches that could better guide these specific cell populations towards enhanced cartilage or soft tissue formation.

Key messages: We found that most clinical trials do not account for cell heterogeneity, nor do they specify the regenerative element recruited, and those that do typically utilize descriptions such as "clots," "elements," and "blood." Furthermore, our review of bone marrow cell populations demonstrates a dramatically heterogenous cell population, including hematopoietic cells, immune cells, fibroblasts, macrophages, and only a small population of MSCs. Finally, the field has developed numerous innovative techniques to enhance the chondrogenic potential (and reduce the anti-regenerative impacts) of these various cell types. We hope this review will guide approaches that account for cellular heterogeneity and improve marrow stimulation techniques to treat chondral defects.

Mouse fetuses generated by in vitro embryo culture and embryo transfer exhibit impaired lung development, altered composition of pulmonary epithelial cells associated with downregulation of several genes involved in lung development and toll-like receptor (TLR) signaling pathway. The aims of the present study were to determine the expression of all TLRs and to examine if the expression of TLRs, along with genes involved in TLR signaling pathway, is altered in the lung tissue of mouse fetuses generated through embryo culture and embryo transfer. Two experimental (EGs) and one control (CG) group were included in the study. Embryos cultured at 5% CO2-95% air for 95 h or less than 24 h were transferred to pseudo-pregnant females to obtain fetuses comprising EGin vitro (n = 18) and EGin vivo (n = 18), respectively. Fetuses obtained from naturally ovulating females on day 18 of pregnancy served as the CG (n = 18). Western blot and immunohistochemistry were used to determine the expression of TLR proteins. The expression of transcripts encoding TLRs, and the genes involved in TLR signaling pathway (Lbp, Pik3r1, Pik3cb, Nfkbia, and Fos), was determined using qRT-PCR. While all TLRs were expressed by cells lining the bronchial/bronchiolar epithelium of lung tissues in all groups, some of the TLRs were expressed in a specific pattern. When compared to CG, the expression of transcripts encoding TLR-2, -3, -4, -5, -7, -8, -9, -12, -13, Lbp, Pik3r1, Pik3cb, Nfkbia, and Fos was significantly downregulated in both EGs. It appears that stress imposed on embryos at preimplantation stages of development is associated with downregulation of TLRs, along with some of the genes involved in TLR signaling pathway, in the lung tissue during the perinatal period. It remains to be determined if downregulation of TLRs, along with the genes involved in TLR signaling pathway, has any functional consequences in the adult lung tissue.

Introduction: Ascending aortic aneurysm is a serious health risk. In order to study ascending aortic aneurysms, elastase and calcium ion treatment for aneurysm formation are mainly used, but their aneurysm formation time is long and the aneurysm formation rate is low. Thus, this study aimed to construct a rat model of ascending aorta aneurysm with a short modeling time and high aneurysm formation rate, which may mimic the pathological processes of human ascending aorta aneurysm.

Methods: Cushion needles with different pipe diameters (1.0, 1.2, 1.4, and 1.6 mm) were used to establish a human-like rat model of ascending aortic aneurysm by narrowing the ascending aorta of rats and increasing the force of blood flow on the vessel wall. The vascular diameters were evaluated using color Doppler ultrasonography after 2 weeks. The characteristics of ascending aortic aneurysm in rats were detected by Masson's trichrome staining, Verhoeff's Van Gieson staining, and hematoxylin and eosin staining, while real-time polymerase chain reaction was utilized to assess the total RNA of cytokine interleukin-1β, interleukin 6, transforming growth factor-beta 1, and metalloproteinase 2.

Results: Two weeks after surgery, the ultrasound images and the statistical analysis demonstrated that the diameter of the ascending aorta in rats increased more than 1.5 times, similar to that in humans, indicating the success of animal modeling of ascending aortic aneurysm. Moreover, the optimal constriction diameter of the ascending aortic aneurysm model is 1.4 mm by the statistical analysis of the rate of ascending aortic aneurysm and mortality rate in rats with different constriction diameters.

Conclusions: The human-like ascending aortic aneurysm model developed in this study can be used for the studies of the pathological processes and mechanisms of ascending aortic aneurysm in a more clinically relevant fashion.