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Tissue & Cell Jun 2024Dental pulp stem cells (DPSCs) originate from the neural crest and the present mesenchymal phenotype showed self-renewal capabilities and can differentiate into at least... (Review)
Review
Dental pulp stem cells (DPSCs) originate from the neural crest and the present mesenchymal phenotype showed self-renewal capabilities and can differentiate into at least three lineages. DPSCs are easily isolated with minimal harm, no notable ethical constraints, and without general anesthesia to the donor individuals. Furthermore, cryopreservation of DPSCs provides this opportunity for autologous transplantation in future studies without fundamental changes in stemness, viability, proliferation, and differentiating features. Current approaches for pulp tissue regeneration include pulp revascularization, cell-homing-based regenerative endodontic treatment (RET), cell-transplantation-based regenerative endodontic treatment, and allogeneic transplantation. In recent years, a novel technology, organoid, provides a mimic physiological condition and tissue construct that can be applied for tissue engineering, genetic manipulation, disease modeling, single-cell high throughput analysis, living biobank, cryopreserving and maintaining cells, and therapeutic approaches based on personalized medicine. The organoids can be a reliable preclinical prediction model for evaluating cell behavior, monitoring drug response or resistance, and comparing healthy and pathological conditions for therapeutic and prognostic approaches. In the current review, we focused on the promising application of 3D organoid technology based on DPSCs in oral and maxillofacial tissue regeneration. We discussed encountering challenges and limitations, and found promising solutions to overcome obstacles.
PubMed: 38936200
DOI: 10.1016/j.tice.2024.102451 -
Biomedicine & Pharmacotherapy =... Jun 2024Injury of a peripheral nerve (PNI) leads to both ischemic and inflammatory alterations. Sciatic nerve injury (SNI) represents the most widely used model for PNI....
Injury of a peripheral nerve (PNI) leads to both ischemic and inflammatory alterations. Sciatic nerve injury (SNI) represents the most widely used model for PNI. Mesenchymal stem cell-based therapy (MSCs) has convenient properties on PNI by stimulating the nerve regeneration. Melatonin has cytoprotective activity. The neuroprotective characteristics of MSCs and melatonin separately or in combination remain a knowledge need. In the rats-challenged SNI, therapeutic roles of intralesional MSCs and intraperitoneal melatonin injections were evaluated by functional assessment of peripheral nerve regeneration by walking track analysis involving sciatic function index (SFI) and two electrophysiological tests, electromyography and nerve conduction velocity, as well as measurement of antioxidant markers in serum, total antioxidant capacity (TAC) and malondialdehyde, and mRNA expression of brain derived neurotrophic factor (BDNF) in nerve tissues in addition to the histopathological evaluation of nerve tissue. Both individual and combination therapy with MSCs and melatonin therapies could effectively ameliorate this SNI and promote its regeneration as evidenced by improving the SFI and two electrophysiological tests and remarkable elevation of TAC with decline in lipid peroxidation and upregulation of BDNF levels. All of these led to functional improvement of the damaged nerve tissues and good recovery of the histopathological sections of sciatic nerve tissues suggesting multifactorial synergistic approach of the concurrent usage of melatonin and MSCs in PNI. The combination regimen has the most synergistic neuro-beneficial effects in PNI that should be used as therapeutic option in patients with PNI to boost their quality of life.
PubMed: 38936196
DOI: 10.1016/j.biopha.2024.117015 -
Biomedicine & Pharmacotherapy =... Jun 2024Acute kidney injury (AKI), characterized by a sudden decline in kidney function involving tubular damage and epithelial cell death, can lead to progressive tissue...
Acute kidney injury (AKI), characterized by a sudden decline in kidney function involving tubular damage and epithelial cell death, can lead to progressive tissue fibrosis and chronic kidney disease due to interstitial fibroblast activation and tissue repair failures that lack direct treatments. After an AKI episode, surviving renal tubular cells undergo cycles of dedifferentiation, proliferation and redifferentiation while fibroblast activity increases and then declines to avoid an exaggerated extracellular matrix deposition. Appropriate tissue recovery versus pathogenic fibrotic progression depends on fine-tuning all these processes. Identifying endogenous factors able to affect any of them may offer new therapeutic opportunities to improve AKI outcomes. Galectin-8 (Gal-8) is an endogenous carbohydrate-binding protein that is secreted through an unconventional mechanism, binds to glycosylated proteins at the cell surface and modifies various cellular activities, including cell proliferation and survival against stress conditions. Here, using a mouse model of AKI induced by folic acid, we show that pre-treatment with Gal-8 protects against cell death, promotes epithelial cell redifferentiation and improves renal function. In addition, Gal-8 decreases fibroblast activation, resulting in less expression of fibrotic genes. Gal-8 added after AKI induction is also effective in maintaining renal function against damage, improving epithelial cell survival. The ability to protect kidneys from injury during both pre- and post-treatments, coupled with its anti-fibrotic effect, highlights Gal-8 as an endogenous factor to be considered in therapeutic strategies aimed at improving renal function and mitigating chronic pathogenic progression.
PubMed: 38936192
DOI: 10.1016/j.biopha.2024.116923 -
PloS One 2024Colorectal cancer (CRC) is the third most common malignancy cause of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) promotes cancer...
Colorectal cancer (CRC) is the third most common malignancy cause of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) promotes cancer metastasis and a tumour-based Glasgow EMT score was associated with adverse clinical features and poor prognosis. In this study, the impact of using the established five tumour-based EMT markers consisting of E-cadherin (E-cad), β-catenin (β-cat), Snail, Zeb-1, and Fascin in combination with the stromal periostin (PN) on the prediction of CRC patients' prognosis were invesigated. Formalin-fixed paraffin-embedded tissues of 202 CRC patients were studies the expressions of E-cad, β-cat, Snail, Zeb-1, Fascin, and PN by immunohistochemistry. Individually, cytoplasmic Fascin (Fc), cytoplasmic Snail (Sc), nuclear Snail (Sn), stromal Snail (Ss), and stromal PN (Ps) were significantly associated with reduced survival. A combination of Ps with Fc, Fs, and Sn was observed in 2 patterns including combined Fc, Fs, and Ps (FcFsPs) and Fc, Sn, and Ps (FcSnPs). These combinations enhanced the prognostic power compared to individual EMT markers and were independent prognostic markers. As the previously established scoring method required five markers and stringent criteria, its clinical use might be limited. Therefore, using these novel combined prognostic markers, either FcFsPs or FcSnPs, may be useful in predicting CRC patient outcomes.
Topics: Humans; Colorectal Neoplasms; Snail Family Transcription Factors; Cell Adhesion Molecules; Prognosis; Female; Male; Middle Aged; Carrier Proteins; Microfilament Proteins; Epithelial-Mesenchymal Transition; Aged; Biomarkers, Tumor; Adult; Cadherins; Transcription Factors; beta Catenin; Aged, 80 and over; Periostin
PubMed: 38935747
DOI: 10.1371/journal.pone.0304666 -
ACS Biomaterials Science & Engineering Jun 2024Bone defects typically result in bone nonunion, delayed or nonhealing, and localized dysfunction, and commonly used clinical treatments (i.e., autologous and allogeneic...
Bone defects typically result in bone nonunion, delayed or nonhealing, and localized dysfunction, and commonly used clinical treatments (i.e., autologous and allogeneic grafts) have limited results. The multifunctional bone tissue engineering scaffold provides a new treatment for the repair of bone defects. Herein, a three-dimensional porous composite scaffold with stable mechanical support, effective antibacterial and hemostasis properties, and the ability to promote the rapid repair of bone defects was synthesized using methacrylated carboxymethyl chitosan and icariin-loaded poly-l-lactide/gelatin short fibers (M-CMCS-SFs). Icariin-loaded SFs in the M-CMCS scaffold resulted in the sustained release of osteogenic agents, which was beneficial for mechanical reinforcement. Both the porous structure and the use of chitosan facilitate the effective absorption of blood and fluid exudates. Moreover, its superior antibacterial properties could prevent the occurrence of inflammation and infection. When cultured with bone mesenchymal stem cells, the composite scaffold showed a promotion in osteogenic differentiation. Taken together, such a multifunctional composite scaffold showed comprehensive performance in antibacterial, hemostasis, and bone regeneration, thus holding promising potential in the repair of bone defects and related medical treatments.
PubMed: 38935742
DOI: 10.1021/acsbiomaterials.4c00707 -
Advanced Biology Jun 2024New-QiangGuYin (N-QGY), the addition of sea buckthorn on the basis of QGY formula, is herbal formula widely used clinically in China for the treatment of osteoporosis...
New-QiangGuYin (N-QGY), the addition of sea buckthorn on the basis of QGY formula, is herbal formula widely used clinically in China for the treatment of osteoporosis (OP), but its mechanism warrants further exploration. The mechanisms of QGY and N-QGY in the treatment of OP are probed from the perspective of osteoclast-osteoblast balance. Thirty Sprague-Dawley rats are randomly divided into N-QGY group, QGY group, and Control group. Beyond control rats that orally took normal saline, other rats are orally administered with isometric N-QGY or QGY twice every day for 3 days. The drug-containing serum and control serum are prepared and their effects on osteoclast-derived exosome secretion are determined by bicinchoninic acid assay (BCA), nanoparticle tracking analysis, and Western blot. GW4869 and Interleukin-1β (IL-1β) are adopted as the exosome inhibitor and inducer, respectively. Exosome uptake, cell counting kit-8, alkaline phosphatase (ALP) staining, alizarin red staining, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and Western blot are performed to examine the effects of altered osteoclast exosome content on osteogenic differentiation of mesenchymal stem cells (MSCs). N-QGY, QGY, and GW4869 inhibit osteoclast-derived exosome secretion and exosome uptake by MSCs, whereas IL-1β exerted the opposite effects (p < 0.05). Different from IL-1β, N-QGY, QGY, and GW4869 partially elevated MSC viability, osteocalcin secretion, ALP, RUNX Family Transcription Factor 2 (RUNX2) and Osteopontin (OPN) expressions, and calcium deposition in the osteoclast-MSCs coculture system (p < 0.05). Mechanically, osteoclasts increased Notum protein level but decreased β-catenin level, which is enhanced by IL-1β but is reversed by GW4869, QGY, and N-QGY (p < 0.05). And the effect of N-QGY is more conspicuous than that of QGY (P<0.05). N-QGY-containing serum inhibits exosome levels in osteoclasts, thereby enhancing osteogenic differentiation of MSCs via inhibition of Notum protein and promotion of β-catenin protein.
PubMed: 38935529
DOI: 10.1002/adbi.202400166 -
Current Opinion in Gastroenterology Jun 2024Although the mucosal barrier serves as a primary interface between the environment and host, little is known about the repair of acute, superficial lesions or deeper,...
PURPOSE OF REVIEW
Although the mucosal barrier serves as a primary interface between the environment and host, little is known about the repair of acute, superficial lesions or deeper, persistent lesions that if not healed, can be the site of increased permeability to luminal antigens, inflammation, and/or neoplasia development.
RECENT FINDINGS
Studies on acute superficial lesions have been sparse in the past year, with more focus given to novel mechanisms of mucosal protection, and the way in which mature epithelial cells or committed stem cells dedifferentiate, reprogram, proliferate, and then regenerate the gastroduodenal mucosa after injury. For this, adenoviral therapy showed organ specific targeting with mRNA and protein expression of effectors to protect against mucosal injury and ulceration. A large database of plant-based agents known to protect against injury and ulceration was published, along with studies using plant-based compounds delivered with alginates, polysaccharide/gel floating rafts, or incorporated into nanoparticles or green carbon dots to improve targeting and retention at the ulcerated lesion. With RNA technology developing rapidly, particularly single-cell RNA sequencing, important and novel data was forthcoming on mucosal regeneration. In particular, the role of interleukin-17 hub proteins in mucosal healing was highlighted. The presence and role of injury reserve cells was determined, as was the composition of ligand gradients for cell differentiation in both stomach and duodenum. The role of amphiregulin in parietal cell differentiation from lineage-restricted stem cells and the Yap1 gene signature in metaplasia vs. healing ulcers were of particular importance. Additionally, studies unveiled the important role of mesenchymal stromal cells in differentiation and repair mechanisms, in Muse cells as an exciting new therapy for mucosal repair after injury, and the role of sympathetic neurons in activating the immune system to regulate mucosal repair mechanisms.
SUMMARY
Recent studies highlight novel mechanisms that promote mucosal regeneration after injury of the gastroduodenal mucosa.
PubMed: 38935320
DOI: 10.1097/MOG.0000000000001049 -
In Vitro Cellular & Developmental... Jun 2024Decellularized tissues are an attractive scaffolds for 3D tissue engineering. Decellularized animal tissues have certain limitations such as the availability of tissue,...
Decellularized tissues are an attractive scaffolds for 3D tissue engineering. Decellularized animal tissues have certain limitations such as the availability of tissue, high costs and ethical concerns related to the use of animal sources. Plant-based tissue decellularized scaffolds could be a better option to overcome the problem. The leaves of different plants offer a unique opportunity for the development of tissue-specific scaffolds, depending on the reticulate or parallel veination. Herein, we decellularized spinach leaves and employed these for the propagation and osteogenic differentiation of dental pulp stem cells (DPSCs). DPSCs were characterized by using mesenchymal stem cell surface markers CD90, CD105 and CD73 and CD34, CD45 and HLA-DR using flow cytometry. Spinach leaves were decellularized using ethanol, NaOH and HCL. Cytotoxicity of spinach leaf scaffolds were analysed by MTT assay. Decellularized spinach leaves supported dental pulp stem cell adhesion, proliferation and osteogenic differentiation. Our data demonstrate that the decellularized spinach cellulose scaffolds can stimulate the growth, proliferation and osteogenic differentiation of DPSCs. In this study, we showed the versatile nature of decellularized plant leaves as a biological scaffold and their potential for bone regeneration in vitro.
PubMed: 38935255
DOI: 10.1007/s11626-024-00937-9 -
Journal of the Science of Food and... Jun 2024Betel nut chewing is a significant risk factor for oral cancer due to arecoline, its primary active component. Resveratrol, a non-flavonoid polyphenol, possesses...
BACKGROUND
Betel nut chewing is a significant risk factor for oral cancer due to arecoline, its primary active component. Resveratrol, a non-flavonoid polyphenol, possesses anti-cancer properties. It has been shown to inhibit arecoline-induced oral malignant cells in preliminary experiments but the underlying mechanism remains unclear. This research therefore aimed to explore the potential therapeutic targets of resveratrol in treating arecoline-induced oral cancer.
METHODS
Data mining identified common targets and hub targets of resveratrol in arecoline-induced oral cancer. Gene set variation analysis (GSVA) was used to score and validate the expression and clinical significance of these hub targets in head and neck cancer (HNC) tissues. Molecular docking analysis was conducted on the hub targets. The effect of resveratrol intervention on hub targets was verified by experiments.
RESULTS
Sixty-one common targets and 15 hub targets were identified. Hub targets were highly expressed in HNC and were associated with unfavorable prognoses. They played a role in HNC metastasis, epithelial-mesenchymal transition, and invasion. Their expression also affected immune cell infiltration and correlated negatively with sensitivity to chemotherapeutic agents such as bleomycin and docetaxel. Experiments demonstrated that resveratrol down-regulated the expression of the hub targets, inhibited their proliferation and invasion, and induced apoptosis.
CONCLUSION
Resveratrol inhibits the arecoline-induced malignant phenotype of oral epithelial cells by regulating the expression of some target genes, suggesting that resveratrol may be used not only as an adjuvant treatment for oral cancer, but also as an adjuvant for oral cancer prevention due to its low toxicity and high efficacy. © 2024 Society of Chemical Industry.
PubMed: 38934557
DOI: 10.1002/jsfa.13664 -
Cytotechnology Aug 2024Cardiovascular diseases remain as the most common cause of death worldwide. To reveal the underlying mechanisms in varying cardiovascular diseases, in vitro models with...
UNLABELLED
Cardiovascular diseases remain as the most common cause of death worldwide. To reveal the underlying mechanisms in varying cardiovascular diseases, in vitro models with cells and supportive biomaterial can be designed to recapitulate the essential components of human heart. In this study, we analyzed whether 3D co-culture of cardiomyocytes (CM) with vascular network and with adipose tissue-derived mesenchymal stem/stromal cells (ASC) can support CM functionality. CM were cultured with either endothelial cells (EC) and ASC or with only ASC in hydrazide-modified gelatin and oxidized gellan gum hybrid hydrogel to form cardiovascular multiculture and myocardial co-culture, respectively. We studied functional characteristics of CM in two different cellular set-ups and analyzed vascular network formation, cellular morphology and orientation. The results showed that gellan gum-gelatin hydrogel supports formation of two different cellular networks and functional CM. We detected formation of a modest vascular network in cardiovascular multiculture and extensive ASC-derived alpha smooth muscle actin -positive cellular network in multi- and co-culture. iPSC-CM showed elongated morphology, partly aligned orientation with the formed networks and presented normal calcium transients, beating rates, and contraction and relaxation behavior in both setups. These 3D cardiac models provide promising platforms to study (patho) physiological mechanisms of cardiovascular diseases.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s10616-024-00630-5.
PubMed: 38933872
DOI: 10.1007/s10616-024-00630-5