World journal of stem cells最新文献

Background: Mesenchymal stromal cells (MSCs) are multipotent cell populations obtained from fetal and adult tissues. They share some characteristics with limb bud mesodermal cells such as differentiation potential into osteogenic, chondrogenic, and tenogenic lineages and an embryonic mesodermal origin. Although MSCs differentiate into skeletal-related lineages in vitro, they have not been shown to self-organize into complex skeletal structures or connective tissues, as in the limb. In this work, we demonstrate that the expression of molecular markers to commit MSCs to skeletal lineages is not sufficient to generate skeletal elements in vivo.

Aim: To evaluate the potential of MSCs to differentiate into skeletal lineages and generate complex skeletal structures using the recombinant limb (RL) system.

Methods: We used the experimental system of RLs from dissociated-reaggregated human placenta (PL) and umbilical cord blood (UCB) MSCs. After being harvested and reaggregated in a pellet, cultured cells were introduced into an ectodermal cover obtained from an early chicken limb bud. Next, this filled ectoderm was grafted into the back of a donor chick embryo. Under these conditions, the cells received and responded to the ectoderm's embryonic signals in a spatiotemporal manner to differentiate and pattern into skeletal elements. Their response to differentiation and morphogenetic signals was evaluated by quantitative polymerase chain reaction, histology, immunofluorescence, scanning electron microscopy, and in situ hybridization.

Results: We found that human PL-MSCs and UCB-MSCs constituting the RLs expressed chondrogenic, osteogenic, and tenogenic molecular markers while differentially committing into limb lineages but could not generate complex structures in vivo. MSCs-RL from PL or UCB were committed early to chondrogenic lineage. Nevertheless, the UCB-RL osteogenic commitment was favored, although preferentially to a tenogenic cell fate. These findings suggest that the commitment of MSCs to differentiate into skeletal lineages differs according to the source and is independent of their capacity to generate skeletal elements or connective tissue in vivo. Our results suggest that the failure to form skeletal structures may be due to the intrinsic characteristics of MSCs. Thus, it is necessary to thoroughly evaluate the biological aspects of MSCs and how they respond to morphogenetic signals in an in vivo context.

Conclusion: PL-MSCs and UCB-MSCs express molecular markers of differentiation into skeletal lineages, but they are not sufficient to generate complex skeletal structures in vivo.

Background: Scar formation and loss of cutaneous appendages are the greatest challenges in cutaneous wound healing. Previous studies have indicated that antler reserve mesenchyme (RM) cells and their conditioned medium improved regenerative wound healing with partial recovery of cutaneous appendages.

Aim: To develop hydrogels from the antler RM matrix (HARM) and evaluate the effect on wound healing.

Methods: We prepared the hydrogels from the HARM via enzymatic solubilization with pepsin. Then we investigated the therapeutic effects of HARM on a full-thickness cutaneous wound healing rat model using both local injections surrounding the wound and topical wound application.

Results: The results showed that HARM accelerated wound healing rate and reduced scar formation. Also, HARM stimulated the regeneration of cutaneous appendages and blood vessels, and reduced collagen fiber aggregation. Further study showed that these functions might be achieved via creating a fetal-like niche at the wound site. The levels of fetal wound healing-related genes, including Collagen III and TGFβ3 treated with HARM were all increased, while the expression levels of Collagen I, TGFβ1, and Engrailed 1 were decreased in the healing. Moreover, the number of stem cells was increased in the fetal-like niche created by HARM, which may contribute to the regeneration of cutaneous appendages.

Conclusion: Overall, we successfully developed an injectable hydrogel made from antler RM matrix for the regenerative repair of full-thickness cutaneous wounds. We uncovered the molecular mechanism of the hydrogels in promoting regenerative wound healing, and thus pave the way for HARM to be developed for the clinic use.

Background: Accumulating evidence suggests that the maxillary process, to which cranial crest cells migrate, is essential to tooth development. Emerging studies indicate that Cd271 plays an essential role in odontogenesis. However, the underlying mechanisms have yet to be elucidated.

Aim: To establish the functionally heterogeneous population in the maxillary process, elucidate the effects of Cd271 deficiency on gene expression differences.

Methods: p75NTR knockout (Cd271^-/-) mice (from American Jackson laboratory) were used to collect the maxillofacial process tissue of p75NTR knockout mice, and the wild-type maxillofacial process of the same pregnant mouse wild was used as control. After single cell suspension, the cDNA was prepared by loading the single cell suspension into the 10x Genomics Chromium system to be sequenced by NovaSeq6000 sequencing system. Finally, the sequencing data in Fastq format were obtained. The FastQC software is used to evaluate the quality of data and CellRanger analyzed the data. The gene expression matrix is read by R software, and Seurat is used to control and standardize the data, reduce the dimension and cluster. We search for marker genes for subgroup annotation by consulting literature and database; explore the effect of p75NTR knockout on mesenchymal stem cells (MSCs) gene expression and cell proportion by cell subgrouping, differential gene analysis, enrichment analysis and protein-protein interaction network analysis; understand the interaction between MSCs cells and the differentiation trajectory and gene change characteristics of p75NTR knockout MSCs by cell communication analysis and pseudo-time analysis. Last we verified the findings single cell sequencing in vitro.

Results: We identified 21 cell clusters, and we re-clustered these into three subclusters. Importantly, we revealed the cell-cell communication networks between clusters. We clarified that Cd271 was significantly associated with the regulation of mineralization.

Conclusion: This study provides comprehensive mechanistic insights into the maxillary- process-derived MSCs and demonstrates that Cd271 is significantly associated with the odontogenesis in mesenchymal populations.

Brain diseases affect 1 in 6 people worldwide. These diseases range from acute neurological conditions such as stroke to chronic neurodegenerative disorders such as Alzheimer's disease. Recent advancements in tissue-engineered brain disease models have overcome many of the different shortcomings associated with the various animal models, tissue culture models, and epidemiologic patient data that are commonly used to study brain disease. One innovative method by which to model human neurological disease is via the directed differentiation of human pluripotent stem cells (hPSCs) to neural lineages including neurons, astrocytes, and oligodendrocytes. Three-dimensional models such as brain organoids have also been derived from hPSCs, offering more physiological relevance due to their incorporation of various cell types. As such, brain organoids can better model the pathophysiology of neural diseases observed in patients. In this review, we will emphasize recent developments in hPSC-based tissue culture models of neurological disorders and how they are being used to create neural disease models.

The high incidence and disability rates of stroke pose a heavy burden on society. Inflammation is a significant pathological reaction that occurs after an ischemic stroke. Currently, therapeutic methods, except for intravenous thrombolysis and vascular thrombectomy, have limited time windows. Mesenchymal stem cells (MSCs) can migrate, differentiate, and inhibit inflammatory immune responses. Exosomes (Exos), which are secretory vesicles, have the characteristics of the cells from which they are derived, making them attractive targets for research in recent years. MSC-derived exosomes can attenuate the inflammatory response caused by cerebral stroke by modulating damage-associated molecular patterns. In this review, research on the inflammatory response mechanisms associated with Exos therapy after an ischemic injury is discussed to provide a new approach to clinical treatment.

Osteoarthritis (OA) is a common degenerative joint disease that often involves progressive cartilage degeneration and bone destruction of subchondral bone. At present, clinical treatment is mainly for pain relief, and there are no effective methods to delay the progression of the disease. When this disease progresses to the advanced stage, the only treatment option for most patients is total knee replacement surgery, which causes patients great pain and anxiety. As a type of stem cell, mesenchymal stem cells (MSCs) have multidirectional differentiation potential. The osteogenic differentiation and chondrogenic differentiation of MSCs can play vital roles in the treatment of OA, as they can relieve pain in patients and improve joint function. The differentiation direction of MSCs is accurately controlled by a variety of signaling pathways, so there are many factors that can affect the differentiation direction of MSCs by acting on these signaling pathways. When MSCs are applied to OA treatment, the microenvironment of the joints, injected drugs, scaffold materials, source of MSCs and other factors exert specific impacts on the differentiation direction of MSCs. This review aims to summarize the mechanisms by which these factors influence MSC differentiation to produce better curative effects when MSCs are applied clinically in the future.

Mesenchymal stem cells (MSCs) can differentiate into various tissue cell types including bone, adipose, cartilage, and muscle. Among those, osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies. Moreover, the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing. Recently, with the gradual recognition of adipokines, the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism, inflammation, immune regulation, energy disorders, and bone homeostasis. At the same time, the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely. Therefore, this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs, emphasizing bone formation and bone regeneration.

Lung cancer is the major cause of cancer-related deaths worldwide, it has one of the lowest 5-year survival rate, mainly because it is diagnosed in the late stage of the disease. Lung cancer is classified into two groups, small cell lung cancer (SCLC) and non-SCLC (NSCLC). In turn, NSCLC is categorized into three distinct cell subtypes: Adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. NSCLC is the most common lung cancer, accounting for 85% of all lung cancers. Treatment for lung cancer is linked to the cell type and stage of the disease, involving chemotherapy, radiation therapy, and surgery. Despite improvements in therapeutic treatments, lung cancer patients show high rates of recurrence, metastasis, and resistance to chemotherapy. Lung stem cells (SCs) are undifferentiated cells capable of self-renewal and proliferation, are resistant to chemotherapy and radiotherapy and, due to their properties, could be involved in the development and progression of lung cancer. The presence of SCs in the lung tissue could be the reason why lung cancer is difficult to treat. The identification of lung cancer stem cells biomarkers is of interest for precision medicine using new therapeutic agents directed against these cell populations. In this review, we present the current knowledge on lung SCs and discuss their functional role in the initiation and progression of lung cancer, as well as their role in tumor resistance to chemotherapy.

Background: Bone marrow-derived mesenchymal stem cells (MSCs) show podocyte-protective effects in chronic kidney disease. Calycosin (CA), a phytoestrogen, is isolated from Astragalus membranaceus with a kidney-tonifying effect. CA preconditioning enhances the protective effect of MSCs against renal fibrosis in mice with unilateral ureteral occlusion. However, the protective effect and underlying mechanism of CA-pretreated MSCs (MSCs^CA) on podocytes in adriamycin (ADR)-induced focal segmental glomerulosclerosis (FSGS) mice remain unclear.

Aim: To investigate whether CA enhances the role of MSCs in protecting against podocyte injury induced by ADR and the possible mechanism involved.

Methods: ADR was used to induce FSGS in mice, and MSCs, CA, or MSCs^CA were administered to mice. Their protective effect and possible mechanism of action on podocytes were observed by Western blot, immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction. In vitro, ADR was used to stimulate mouse podocytes (MPC5) to induce injury, and the supernatants from MSC-, CA-, or MSCs^CA-treated cells were collected to observe their protective effects on podocytes. Subsequently, the apoptosis of podocytes was detected in vivo and in vitro by Western blot, TUNEL assay, and immunofluorescence. Overexpression of Smad3, which is involved in apoptosis, was then induced to evaluate whether the MSCs^CA-mediated podocyte protective effect is associated with Smad3 inhibition in MPC5 cells.

Results: CA-pretreated MSCs enhanced the protective effect of MSCs against podocyte injury and the ability to inhibit podocyte apoptosis in ADR-induced FSGS mice and MPC5 cells. Expression of p-Smad3 was upregulated in mice with ADR-induced FSGS and MPC5 cells, which was reversed by MSC^CA treatment more significantly than by MSCs or CA alone. When Smad3 was overexpressed in MPC5 cells, MSCs^CA could not fulfill their potential to inhibit podocyte apoptosis.

Conclusion: MSCs^CA enhance the protection of MSCs against ADR-induced podocyte apoptosis. The underlying mechanism may be related to MSCs^CA-targeted inhibition of p-Smad3 in podocytes.

Cancer stem cells (CSCs) are a small proportion of the cells that exist in cancer tissues. They are considered to be the culprit of tumor genesis, development, drug resistance, metastasis and recurrence because of their self-renewal, proliferation, and differentiation potential. The elimination of CSCs is thus the key to cure cancer, and targeting CSCs provides a new method for tumor treatment. Due to the advantages of controlled sustained release, targeting and high biocompatibility, a variety of nanomaterials are used in the diagnosis and treatments targeting CSCs and promote the recognition and removal of tumor cells and CSCs. This article mainly reviews the research progress of nanotechnology in sorting CSCs and nanodrug delivery systems targeting CSCs. Furthermore, we identify the problems and future research directions of nanotechnology in CSC therapy. We hope that this review will provide guidance for the design of nanotechnology as a drug carrier so that it can be used in clinic for cancer therapy as soon as possible.