American journal of stem cells最新文献

Cancer stem cells (CSCs) are a unique population of cells found within tumors that are able to self-renew, restore the original heterogeneity of a tumor following treatment, and show increased tumorigenic potential when compared to other cancer cells. It is thought that they are responsible for the recurrence of tumors as well as the resistance to treatment that is seen clinically. CSCs are known to be involved in head and neck cancer (HNCs) specifically, as evidence for their existence can be found in head and neck squamous cell carcinoma (HNSCC), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC), among others. Here, findings from various approaches to identifying and targeting CSCs and their downstream effectors in HNC are summarized, with an emphasis on recent advancements. Prognostic and therapeutic markers are discussed for each specific type of HNC, and novel treatment strategies and current clinical trials involving CSCs are detailed as well. The information provided here is intended to further the research on this important topic and lead to clinical impact in the battle against HNC.

The properties of hematopoietic stem and progenitor cells (HSPCs), including self-renewal and pluripotency, have been extensively studied. These features have been explored in the management of several haematological disorders and malignancies. Although their role as precursors of innate immune cells is well understood, little is known about their direct participation in host immune response. In this review, we explicate the direct role of HSPCs in the host immune response and highlight therapeutic options for the infectious disease burden that is currently ravaging the world, including COVID-19.

Historically, primordial germ cells (PGCs) have been a good model to study pluripotency. Despite their low numbers and limited accessibility in the mouse embryo, they can be easily and rapidly reprogrammed at high efficiency with external physicochemical factors and do not require transcription factor transfection. Employing this model to deepen our understanding of cell reprogramming, we specifically aimed to determine the relevance of Ca²⁺ signal transduction pathway components in the reprogramming process. Our results showed that PGC reprogramming requires a normal extracellular [Ca²⁺] range, in contrast to neoplastic or transformed cells, which can continue to proliferate in Ca²⁺-deficient media, differentiating normal reprogramming from neoplastic transformation. Our results also showed that a spike in extracellular [Ca²⁺] of 1-3 mM can directly reprogram PGC. Intracellular manipulation of Ca²⁺ signal transduction pathway components revealed that inhibition of classical Ca²⁺ and diacylglycerol (DAG)-dependent PKCs, or intriguingly, of only the novel DAG-dependent PKC, PKCε, were able to induce reprogramming. PKCε inhibition changed the metabolism of PGCs toward glycolysis, increasing the proportion of inactive mitochondria. This metabolic switch from oxidative phosphorylation to glycolysis is mediated by hypoxia-inducible factors (HIFs), given we found upregulation of both HIF1α and HIF2α in the first 48 hours of culturing. PKCε inhibition did not change the classical pluripotency gene expression of PGCs, Oct4, or Nanog. PKCε inhibition changed the histone acetylation of PGCs, with histones H2B, H3, and H4 becoming acetylated in PKCε-inhibited cultures (markers were H2BacK20, H3acK9, and H4acK5K8, K12, K16), suggesting that reprogramming by PKCε inhibition is mediated by histone acetylation.

Introduction: Mesenchymal stem cells (MSCs) are able to differentiate into several cell lineages including skeletal muscle. In addition to their differentiation capacities, they have the ability to transfer their content genomic information horizontally through their exosomes and fusion abilities, as we have shown in our previous clinic study on Duchenne Muscular Dystrophy (DMD) patients, dystrophin expression increased after MSC treatment. Therefore, this study aimed to compare the transcriptomic properties of Wharton's jelly derived (WJ-) MSC and Adipose tissue (AT-) derived MSC, which are the two most preferred sources in MSC treatments applied in DMD.

Methods: Both MSC cell lines obtained from ATCC (PCS-500-010; PCS-500-011) were characterized by flow cytometry then WJ-MSC and AT-MSC cell lines were sequenced via RNA-SEQ. R language was used to obtain the differentially expressed genes (DEGs) and differentially expressed miRNAs, respectively. Additionally, in order to support the results of our study, a gene expression profile data set of DMD patients (GSE1004) were acquired from Gene Expression Omnibus (GEO) database.

Results: Here, we demonstrated that activated WNT signaling and downregulated TGF-β pathways under the control of decreased mir-24 which are involved in myogenic differentiation are differentially expressed in WJ-MSC. We have shown that the expression of mir-199a-5p, which is known to increase in exosomes of DMD patients, is less in WJ-MSC. Additionally, we have shown activated PI3K/Akt pathway, which is controlling mitochondria transfer via Tunnelling Nanotube as a new perspective in cellular therapies in myodegenerative diseases, in WJ-MSC more than in AT-MSCs.

Conclusion: Summing up, WJ-MSC, which we recommend as an appropriate source candidate due to its immune-regulation properties, stands forward as a preferable source in the cellular treatment of DMD patients due to its transcriptomic aspect.

Introduction: Drug-induced liver injury (DILI) is a leading cause of acute liver injury (ALI). Acetaminophen (also termed paracetamol), can often be found in drugs that may be abused (i.e., prescription for pain relief). Animal experiments have shown that mesenchymal stem cell transplantation can ameliorate or even reverse hepatic injury.

Material and methods: ALI was induced in Wistar rats using paracetamol. ATSCs were transplanted via the intravenous, portal vein, or intrahepatic route directly onto the liver parenchyma. Histological evaluation was conducted to assess drug-induced injury following transplantation. Fluorescence in situ hybridization (FISH) was used to verify the location of stem cells on the liver parenchyma. The effect of those cells on liver regeneration was tested by immunohistochemistry for hepatic growth factor (HGF). In addition, reverse transcription-quantitative PCR (qRT-PCR) was used to assess hepatic growth factor (HGF), hepatic nuclear factor 4α (HNF4α), cytochrome P450 1A2 (CYP1A2) and α-fetoprotein (AFP) mRNA expression.

Results: Immunohistochemical staining for HGF was stronger in the transplanted groups than that in the control group (P<0.001). HNF4α and HGF mRNA levels were increased on day 7 following transplantation (P<0.001 and P=0.009, respectively). CYP1A2 mRNA levels were also increased (P=0.013) in the intravenous groups, while AFP levels were higher in the intrahepatic groups (P=0.006). ATSC transplantation attenuates ALI injury and promotes liver regeneration. Furthermore, expression of specific hepatic enzymes points to ATSC hepatic differentiation.

Conclusion: The study showed the positive effects of transplanted adipose tissue stem cells (ATSCs) on liver regeneration (LG) through hepatotrophic factors. Furthermore, increased expression of hepatic specific proteins was recorded in ATSC transplanted groups that indicate stem cells differentiation into hepatic cells.

Cochlear hair cells (HCs) are the mechanoreceptors of the auditory system, and because these cells cannot be spontaneously regenerated in adult mammals, hearing loss due to HC damage is permanent. However, cochleae of neonatal mice harbor some progenitor cells that retain limited ability to give rise to new HCs in vivo. Here we review the regulatory factors, signaling pathways, and epigenetic factors that have been reported to play roles in HC regeneration in the neonatal mammalian cochlea.

Deafness is one of the major global health problems that seriously affects the quality of human life. At present, there are no successful treatments for deafness caused by cochlear hair cell (HC) damage. The irreversibility of mammalian hearing impairment is that the inner ear's sensory epithelium cannot repair lost hair cells and neurons through spontaneous regeneration. The goal of stem cell therapy for sensorineural hearing loss is to reconstruct the damaged inner ear structure and achieve functional repair. microRNA (miRNA), as a class of highly conserved endogenous non-coding small RNAs, plays an important role in the development of cochlea and HCs. miRNA also participates in the regulation of stem cell proliferation and differentiation, and plays an important role in the process of regeneration of inner ear HCs, miRNA has a broad application prospect of clinical treatment of hearing loss, which is conducive to solving the medical problem of inner ear HC regeneration.

Postnatal mammalian cochlear hair cells (HCs) can be regenerated by direct transdifferentiation or by mitotic regeneration from supporting cells through many pathways, including Atoh1, Wnt, Hedgehog and Notch signaling. However, most new HCs are immature HCs. In this study we used RNA-Seq analysis to compare the differences between the transcriptomes of Atoh1 overexpression-induced new HCs and the native HCs, and to define the factors that might help to promote the maturation of new HCs. As expected, we found Atoh1-induced new HCs had obvious HC characteristics as demonstrated by the expression of HC markers such as Pou4f3 and Myosin VIIA (Myo7a). However, Atoh1-induced new HCs had significantly lower expression of genes that are related to HC function such as Slc26a5 (Prestin), Slc17a8 and Otof. We found that genes related to HC cell differentiation and maturation (Kcnma1, Myo6, Myo7a, Grxcr1, Gfi1, Wnt5a, Fgfr1, Gfi1, Fgf8 etc.) had significantly lower expression levels in new HCs compared to native HCs. In conclusion, we found a set of genes that might regulate the differentiation and maturation of new HCs, and these genes might serve as potential new therapeutic targets for functional HC regeneration and hearing recovery.

Introduction: One of the most common orthodontic problems is maxillary constriction, which is mostly treated by rapid palatal expansion (RPE). However, its high rate of relapse and prolonged retention period have led to some challenges for orthodontists. To encounter these issues, accelerating bone regeneration can provide long-term stability of expanded maxilla. The present study aimed to evaluate the effect of low-level laser therapy (LLLT), bone marrow-derived mesenchymal stem cells (BMSCs) and their combination on promoting bone regeneration of the inter-maxillary suture after RPE in rats.

Materials and method: Total of 60 rats went under RPE treatment. After 7 days, retention period started and interventions (group A, Control (saline); group B, LLLT; group C, BMSCs; group D, LLLT + BMSCs) were performed in the sutural area. After 21 days, radiographic and histological analyses were done. Histological analyses were conducted to evaluate the following criteria of the newly formed bone: the number of osteoblasts, new bone formation, vascularization, connective tissue. Moreover, sutural width was assessed in histologic images. To evaluate bone density at suture area, gray scale and Hounsfield Unit values were measured based on the occlusal radiographic and Micro-Computed topography images respectively.

Results: Only in group C and D, osteoblasts and new bone formation were observed in all of the samples. There were no significant differences among the study groups regarding the post-treatment sutural width (P > 0.05). In the radiographic analysis, only group D showed more bone density compared to the control group (P = 0.022). Similarly, in micro-CT analysis, the most bone density was observed in group D which was significantly more than the control group (P = 0.013).

Conclusion: Our findings suggest that the application of LLLT and BMSCs is the most beneficial approach in accelerating bone regeneration in the inter-maxillary suture.

Two of the leading strategies to prevent cervical cancer are prophylactic human papillomavirus (HPV) vaccination and routine Papanicolaou (Pap) testing. However, regardless of being vaccinated with first-generation (bivalent and quadrivalent) HPV vaccines at the recommended dosing schedule, many women are still found to have low- and high-grade cervical intraepithelial lesions. Studies have shown that this is largely due to: (1) first-generation vaccines only protecting against 70% of high-risk HPV types that cause cervical cancer (HPVs 16/18) and (2) vaccinated women being more prone to infection with non-protected high-risk HPV types than unvaccinated women. Fortunately, the FDA recently approved a nonavalent vaccine that protects against 5 additional high-risk HPV types that cause 20% of cervical cancers (HPVs 31/33/45/52/58), which is the only HPV vaccine currently available in the United States. Although the Advisory Committee on Immunization Practices (ACIP) recommends the nonavalent vaccine in men and women up to the age of 45 years, it does not recommend the nonavalent vaccine in those previously vaccinated with 3 doses of bivalent or quadrivalent vaccine, deeming them "adequately vaccinated". As this population is most at risk, this review serves to provide background and argue for a change in their recommendation.