Tissue engineering and regenerative medicine最新文献

Abstract

Inflammation can occur at the wound site, and immune cells are necessary to trigger wound healing and tissue regeneration after injury. It is partly initiated by the rapid migration of immune cells such as neutrophils, inflammatory monocytes, and macrophages after spinal cord injury (SCI). Secondary inflammation can increase the wound area; thus, the function of tissues below the injury levels. Monocytes can differentiate into macrophages, and the macrophage phenotype can change from a pro-inflammatory phenotype to an anti-inflammatory phenotype. Therefore, various studies on immunomodulation have been performed to suppress secondary inflammation upon nerve damage. This editorial commentary focuses on various therapeutic methods that modulate inflammation and promote functional regeneration after SCI.

Background: Insufficient angiogenesis and the lack of skin appendages are critical challenges in cutaneous wound healing. Stem cell-fabricated cell sheets have become a promising strategy, but cell sheets constructed by a single cell type are inadequate to provide a comprehensive proregenerative microenvironment for wound tissue.

Methods: Based on the communication between cells, in this study, bone marrow mesenchymal stem cells (BMSCs) and hair follicle stem cells (HFSCs) were cocultured to fabricate a composite cell sheet (H/M-CS) for the treatment of full-thickness skin wounds in mice.

Results: Experiments confirmed that there is cell-cell communication between BMSCs and HFSCs, which enhances the cell proliferation and migration abilities of both cell types. Cell-cell talk also upregulates the gene expression of pro-angiogenic-related cytokines in BMSCs and pro-hair follicle-related cytokines in HFSCs, as well as causing changes in the properties of secreted extracellular matrix components.

Conclusions: Therefore, the composite cell sheet is more conducive for cutaneous wound healing and promoting the regeneration of blood vessels and hair follicles.

Background: Repairing soft tissue defects caused by inflammation, tumors, and trauma remains a major challenge for surgeons. Adipose tissue engineering (ATE) provides a promising way to solve this problem.

Methods: This review summarizes the current ATE strategies for soft tissue reconstruction, and introduces potential construction methods for ATE.

Results: Scaffold-based and scaffold-free strategies are the two main approaches in ATE. Although several of these methods have been effective clinically, both scaffold-based and scaffold-free strategies have limitations. The third strategy is a synergistic tissue engineering strategy and combines the advantages of scaffold-based and scaffold-free strategies.

Conclusion: Personalized construction, stable survival of reconstructed tissues and functional recovery of organs are future goals of building tissue-engineered fat for ATE.

Background: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease affecting the cartilage and subchondral bone, leading to temporomandibular joint pain and dysfunction. The complex nature of TMJOA warrants effective alternative treatments, and mesenchymal stem cells (MSCs) have shown promise in regenerative therapies. The aim of this study is twofold: firstly, to ascertain the optimal interferon-gamma (IFN-γ)-primed MSC cell line for TMJOA treatment, and secondly, to comprehensively evaluate the therapeutic efficacy of IFN-γ-primed mesenchymal stem cells derived from the human umbilical cord matrix in a rat model of TMJOA.

Methods: We analyzed changes in the expression of several key genes associated with OA protection in MSC-secreted compounds. Following this, we performed co-culture experiments using a transwell system to predict gene expression changes in primed MSCs in the TMJOA environment. Subsequently, we investigated the efficacy of the selected IFN-γ-primed human umbilical cord matrix-derived MSCs (hUCM-MSCs) for TMJOA treatment in a rat model.

Results: IFN-γ-primed MSCs exhibited enhanced expression of IDO, TSG-6, and FGF-2. Moreover, co-culturing with rat OA chondrocytes induced a decrease in pro-inflammatory and extracellular matrix degradation factors. In the rat TMJOA model, IFN-γ-primed MSCs with elevated IDO1, TSG-6, and FGF2 expression exhibited robust anti-inflammatory and therapeutic capacities, promoting the improvement of the inflammatory environment and cartilage regeneration.

Conclusion: These findings underscore the importance of prioritizing the mitigation of the inflammatory milieu in TMJOA treatment and highlight IFN-γ-primed MSCs secreting these three factors as a promising, comprehensive therapeutic strategy.

Background: Currently, there is no apparent treatment for sarcopenia, which is characterized by diminished myoblast function. We aimed to manufacture exosomes that retain the myogenic differentiation capacity of human fetal cartilage-derived progenitor cells (hFCPCs) and investigate their muscle regenerative efficacy in myoblasts and a sarcopenia rat model.

Methods: The muscle regeneration potential of exosomes (F-Exo) secreted during myogenic differentiation of hFCPCs was compared to human bone marrow mesenchymal stem cells-derived (hBMSCs) exosomes (B-Exo) in myoblasts and sarcopenia rat model. The effect of F-Exo was analyzed through known microRNAs (miRNAs) analysis. The mechanism of action of F-Exo was confirmed by measuring the expression of proteins involved in the Wnt signaling pathway.

Results: F-Exo and B-Exo showed similar exosome characteristics. However, F-Exo induced the expression of muscle markers (MyoD, MyoG, and MyHC) and myotube formation in myoblasts more effectively than B-Exo. Moreover, F-Exo induced greater increases in muscle fiber cross-sectional area and muscle mass compared to B-Exo in a sarcopenia rat. The miR-145-5p, relevant to muscle regeneration, was found in high concentrations in the F-Exo, and RNase pretreatment reduced the efficacy of exosomes. The effects of F-Exo on the expression of myogenic markers in myoblasts were paralleled by the miR-145-5p mimics, while the inhibitor partially negated this effect. F-Exo was involved in the Wnt signaling pathway by enhancing the expression of Wnt5a and β-catenin.

Conclusion: F-Exo improved muscle regeneration by activating the Wnt signaling pathway via abundant miR-145-5p, mimicking the remarkable myogenic differentiation potential of hFCPCs.

Background:

The development and use of human embryonic stem cells (hESCs) in regenerative medicine have been revolutionary, offering significant advancements in treating various diseases. These pluripotent cells, derived from early human embryos, are central to modern biomedical research. However, their application is mired in ethical and regulatory complexities related to the use of human embryos.

Method:

This review utilized key databases such as ClinicalTrials.gov, EU Clinical Trials Register, PubMed, and Google Scholar to gather recent clinical trials and studies involving hESCs. The focus was on their clinical application in regenerative medicine, emphasizing clinical trials and research directly involving hESCs.

Results:

Preclinical studies and clinical trials in various areas like ophthalmology, neurology, endocrinology, and reproductive medicine have demonstrated the versatility of hESCs in regenerative medicine. These studies underscore the potential of hESCs in treating a wide array of conditions. However, the field faces ethical and regulatory challenges, with significant variations in policies and perspectives across different countries.

Conclusion:

The potential of hESCs in regenerative medicine is immense, offering new avenues for treating previously incurable diseases. However, navigating the ethical, legal, and regulatory landscapes is crucial for the continued advancement and responsible application of hESC research in the medical field. Considering both scientific potential and ethical implications, a balanced approach is essential for successfully integrating hESCs into clinical practice.

Background:

Poly(L-lactic acid) (PLLA) is a biodegradable polymer (BP) that replaces conventional petroleum-based polymers. The hydrophobicity of biodegradable PLLA periodontal barrier membrane in wet state can be solved by alloying it with natural polymers. Alloying PLLA with gelatin imparts wet mechanical properties, hydrophilicity, shrinkage, degradability and biocompatibility to the polymeric matrix.

Methods:

To investigate membrane performance in the wet state, PLLA/gelatin membranes were synthesized by varying the gelatin concentration from 0 to 80 wt%. The membrane was prepared by electrospinning.

Results:

At the macroscopic scale, PLLA containing gelatin can tune the wet mechanical properties, hydrophilicity, water uptake capacity (WUC), degradability and biocompatibility of PLLA/gelatin membranes. As the gelatin content increased from 0 to 80 wt%, the dry tensile strength of the membranes increased from 6.4 to 38.9 MPa and the dry strain at break decreased from 1.7 to 0.19. PLLA/gelatin membranes with a gelatin content exceeding 40% showed excellent biocompatibility and hydrophilicity. However, dimensional change (37.5% after 7 days of soaking), poor tensile stress in wet state (3.48 MPa) and rapid degradation rate (73.7%) were observed. The highest WUC, hydrophilicity, porosity, suitable mechanical properties and biocompatibility were observed for the PLLA/40% gelatin membrane.

Conclusion:

PLLA/gelatin membranes with gelatin content less than 40% are suitable as barrier membranes for absorbable periodontal tissue regeneration due to their tunable wet mechanical properties, degradability, biocompatibility and lack of dimensional changes.

Background:

The purpose of this study was to investigate the specific effects of signal transducer and activator of transcription 4 (STAT4)-induced long intergenic nonprotein coding RNA 1278 (LINC01278) on the growth of non-small cell lung cancer (NSCLC) cells involved in the microRNA (miR)-877-5p/activated transcription factor 4 (ATF4) axis.

Methods:

NSCLC tumor tissue and adjacent normal tissue were collected. Human normal lung epithelial cell BEAS-2B and human NSCLC cell lines (H1299, H1975, A549, H2228) were collected. The expression levels of STAT4, LINC01278, miR-877-5p, and ATF4 were detected. A549 cells were screened for subsequent experiments. The proliferation ability of cells was detected by colony formation experiment. Cell apoptosis was tested by flow cytometry. Scratch test and transwell assay were used to detect the migration and invasion ability of cells. Biological function of LINC01278 in NSCLC was confirmed by xenograft experiments.

Results:

Low expression miR-877-5p and high expression of STAT4, LINC01278 and ATF4 were detected in NSCLC. Silenced LINC01278 in A549 cell depressed cell proliferation, migration and invasion, but facilitated cell apoptosis. LINC01278 was positively correlated with STAT4 and could directly bind to miR-877-5p. Upregulating miR-877-5p suppressed NSCLC cell progression, while downregulating miR-877-5p had the opposite effect. Upregulating miR-877-5p abrogated the effects of silenced LINC01278 on NSCLC cell progression. MiR-877-5p targeted ATF4. ATF4 upregulation could partly restore the carcinogenic effect of LINC01278 in vitro and in vivo.

Conclusion:

Our data supports that STAT4-induced upregulation of LINC01278 promotes NSCLC progression by modulating the miR-877-5p/ATF4 axis, suggesting a novel direction for NSCLC treatment.

Graphical abstract

Organoids are essentially an in vitro (lab-grown) three-dimensional tissue culture system model that meticulously replicates the structure and physiology of human organs. A few of the present applications of organoids are in the basic biological research area, molecular medicine and pharmaceutical drug testing. Organoids are crucial in connecting the gap between animal models and human clinical trials during the drug discovery process, which significantly lowers the time duration and cost associated with each stage of testing. Likewise, they can be used to understand cell-to-cell interactions, a crucial aspect of tissue biology and regeneration, and to model disease pathogenesis at various stages of the disease. Lung organoids can be utilized to explore numerous pathophysiological activities of a lung since they share similarities with its function. Researchers have been trying to recreate the complex nature of the lung by developing various “Lung organoids” models.

This article is a systematic review of various developments of lung organoids and their potential progenitors. It also covers the in-depth applications of lung organoids for the advancement of translational research. The review discusses the methodologies to establish different types of lung organoids for studying the regenerative capability of the respiratory system and comprehending various respiratory diseases.

Respiratory diseases are among the most common worldwide, and the growing burden must be addressed instantaneously. Lung organoids along with diverse bio-engineering tools and technologies will serve as a novel model for studying the pathophysiology of various respiratory diseases and for drug screening purposes.