Current stem cell research & therapy最新文献

Background: Limbal stem cells (LSCs) are essential for maintaining corneal transparency and ocular surface integrity. Many external factors or genetic diseases can lead to corneal limbal stem cell deficiency (LSCD), resulting in the loss of barrier and corneal epithelial cell renewal functions. Stem cell transplantation is one of the primary treatments for LSCD, including limbal transplantation and cultivated limbal epithelial transplantation. In addition, a variety of non-limbal stem cell lines have been experimented with for LSCD treatment. Biological scaffolds are also used to support in vitro stem cell culture and transplantation. Here, we review the mechanisms of corneal maintenance by LSCs, the clinical stage and surgical treatment of LSCD, the source of stem cells, and the biological scaffolds required for in vitro culture.

Methods: This study is a narrative retrospective study aimed at collecting available information on various aspects of surgical treatments for LSCD. Relevant literature was searched in a range of online databases, including Web of Science, Scopus, and PubMed from 2005 to March, 2023.

Results: A total of 397 relevant articles were found, and 49 articles with strong relevance to the studies in this paper were obtained and analyzed. Moreover, 11 of these articles were on the concept of LSCD and the mechanism of LESCs maintaining the corneal epithelium, 3 articles on the staging and grading of LSCD, 17 articles on cell transplantation methods and donor cell sources, and 18 articles on scaffolds for delivering stem cells. We also summarized the advantages and disadvantages of different cell transplantation methods and the benefits and limitations of scaffolds based on the above literature.

Conclusion: The treatment of LSCD is determined by the clinical stage and whether it involves monocular or binocular eyes. Appropriate surgical techniques should be taken for LSCD patients in order to reconstruct the ocular surface, relieve symptoms, and restore visual function. Meanwhile, biological scaffolds assist in the ex vivo culture and implantation of stem cells.

In this review, we describe a new avenue that involves the therapeutic use of human adipose tissue. In the past two decades, thousands of papers have described the potential clinical use of human fat and adipose tissue. Moreover, mesenchymal stem cells have been a source of great enthusiasm in clinical studies, and these have generated curiosity at academic levels. On the other hand, they have created considerable commercial business opportunities. High expectations have emerged for curing some recalcitrant diseases or reconstructing anatomically defective human body parts, but several concerns have been raised by generating criticism on the clinical practice that have not been substantiated by rigorous scientific evidence. However, in general, the consensus is that human adipose-derived mesenchymal stem cells inhibit the production of inflammatory cytokines and stimulate the production of anti-inflammatory cytokines. Here, we show that the application of a mechanical elliptical force for several minutes to human abdominal fat activates anti-inflammatory properties and gene-related expression. This may pave the way for new unexpected clinical developments.

Background: Cartilage defects remain a challenge in diseases such as osteoarthritis (OA) and fractures. Scientists have explored the use of hydrogels in conjunction with stem cell technology as a tissue engineering method to treat cartilage defects in joints. In recent years, research into hydrogels containing stem cell technology for cartilage repair has mainly focused on two categories: stem cell-loaded hydrogels and endogenous stem cell recruiting hydrogels. The latter, utilizing cell-free products, represents a novel concept with several advantages, including easier dose standardization, wider sources, and simpler storage. This meta-analysis aims to assess and compare the therapeutic effects of endogenous stem cell recruiting hydrogels and stem cell-loaded hydrogels in promoting articular cartilage regeneration in animal models, with the goal of exploring endogenous stem cell recruiting hydrogels as a promising replacement therapy for knee cartilage regeneration in preclinical animal studies.

Methods: We systematically searched PubMed, Web of Science, Cochrane Library, and Embase until January 2023 using key words related to stem cells, cartilage regeneration and hydrogel. A random-effects meta-analysis was performed to evaluate the therapeutic effect on newborn cartilage formation. Stratified analyses were also carried out by independently classifying trials according to similar characteristics. The level of evidence was determined using the GRADE method.

Results: Twenty-eight studies satisfied the inclusion criteria. Comprehensive analyses revealed that the use of endogenous stem cell recruiting hydrogels significantly promoted the formation of new cartilage in the knee joint, as evidenced by the histological score (3.77, 95% CI 2.40, 5.15; p < 0.0001) and the International Cartilage Repair Society (ICRS) macroscopic score (3.00, 95% CI 1.83, 4.18; p = 0.04), compared with the control group. The stem cell-loaded hydrogels also increased cartilage regeneration in the knee with the histological score (3.13, 95% CI 2.22, 4.04; p = 0.02) and the ICRS macroscopic score (2.49, 95% CI 1.16, 3.82; p = 0.03) in comparison to the control. Significant heterogeneity between studies was observed, and further stratified and sensitivity analyses identified the transplant site and modelling method as the sources of heterogeneity.

Conclusion: The current study indicates that both endogenous stem cell recruiting hydrogels and stem cell loaded hydrogels can effectively promote knee joint cartilage regeneration in animal trials.

Background: Hematologic diseases have seriously threatened human health. Although hematopoietic stem cell transplantation (HSCT) is an effective curative option, the complications, especially graft-versus-host disease (GVHD), are a big problem.

Methods: TNF-α pretreatment of hematopoietic stem cells. Apoptosis was detected by flow cytometry, Transwell, and wound healing assays were used to assess cell migration and invasion, E-selectin expression was observed by fluorescence imaging, the levels of NO were measured by a kit, the expression of Ecadherin, MMP2, and MMP9 was detected in cells by qRT-PCR, and western blot was used to analyze the expression of E-cadherin, CXCL12, MCP-1, MCP-3, MMP2, and MMP9.

Results: TNF-α induces a high apoptosis rate of CD3, CD19, and CD133 and a low apoptosis rate of CD34. The level of Fas and TNF-R1 was significantly high than that of TNF-R2. HSCs treated with TNF- α declined the invasion and migration of HUVECs. E-selectin, MMP2 and MMP9 mRNA levels of HUVECs and MMP2, CXCL12, MCP-1, and MCP-3 were decreased after HSCs-TNF-α treatment, while the E-cadherin mRNA and protein level of HUVECs was enhanced with HSCs-TNF-α treatment.

Conclusion: TNF-α pretreated HSCs can lead to reduced levels of migration, adhesion, and chemokines of HUVECs, thereby declining the inflammatory response and GVHD.

Critical-sized bone defects are a challenging issue during bone regeneration. Bone tissue engineering is aimed to repair such defects using biomimicking scaffolds and stem cells. Electrospinning allows the fabrication of biocompatible, biodegradable, and strengthened scaffolds for bone regeneration. Natural and synthetic polymers, alone or in combination, have been employed to fabricate scaffolds with appropriate properties for the osteogenic differentiation of stem cells. Dental pulps are rich in stem cells, and dental pulp stem cells (DPSCs) have a high capacity for proliferation, differentiation, immunomodulation, and trophic factor expression. Researchers have tried to enhance osteogenesis through scaffold modification approaches, including incorporation or coating with mineral, inorganic materials, and herbal extract components. Among them, the incorporation of nanofibers with hyaluronic acid (HA) has been widely used to promote osteogenesis. In this review, the electrospun scaffolds and their modifications used in combination with DPSCs for bone regeneration are discussed.

Neurodegenerative disorders (NDs) including Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease are all incurable and can only be managed with drugs for the associated symptoms. Animal models of human illnesses help to advance our understanding of the pathogenic processes of diseases. Understanding the pathogenesis as well as drug screening using appropriate disease models of neurodegenerative diseases (NDs) are vital for identifying novel therapies. Human-derived induced pluripotent stem cell (iPSC) models can be an efficient model to create disease in a dish and thereby can proceed with drug screening and identifying appropriate drugs. This technology has many benefits, including efficient reprogramming and regeneration potential, multidirectional differentiation, and the lack of ethical concerns, which open up new avenues for studying neurological illnesses in greater depth. The review mainly focuses on the use of iPSC technology in neuronal disease modeling, drug screening, and cell therapy.

Diabetes mellitus (DM) is a multifaceted pathological condition, which at present is being considered an epidemic disease keeping the rampant rate of its increase in almost all population groups of the world in consideration. Out of the two types of DM described, T1D is characterized as an autoimmune condition that leads to the destruction of pancreatic β-cells by macrophages and T-cells, thereby, adversely affecting the production of insulin. On the other hand, T2D, often caused by insulin resistance, is commonly related to unhealthy habits, and therefore, it can be prevented in most cases. In both of the conditions, high levels of proinflammatory cytokines like IL-6, TNF-α, and INF-ƴ, lead to chronic inflammation, and elevated oxidative stress resulting in apoptosis and destruction of tissues. Although several treatments are available to treat the symptoms, the underlying causes are not well addressed. One of the most promising approaches to tackle the ill effects and the primary causes of DM is mesenchymal stem cell (MSC) therapy. The use of MSC therapy, because of the immunomodulatory and regenerative properties recorded in this type of cells in a number of experiments carried out in animal models and clinical trials of the disease, has reported positive outcomes. This review covers the principal mechanisms of action induced during MSC therapy in reference to the described pathophysiological pathways of both T1D and T2D. In addition, how this therapeutic intervention can counteract the ill effects of this condition leading to the promotion of tissue regeneration has been covered.

Heart failure is still the main complication affecting the prognosis of acute myocardial infarction (AMI), and mesenchymal stem cells (MSCs) are an effective treatment to replace necrotic myocardium and improve cardiac functioning. However, the transplant survival rate of MSCs still presents challenges. In this review, the biological characteristics of MSCs, the progress of mechanism research in the treatment of myocardial infarction, and the advances in improving the transplant survival rate of MSCs in the replacement of necrotic myocardial infarction are systematically described. From a basic to advanced clinical research, MSC transplants have evolved from a pure injection, an exosome injection, the genetic modification of MSCs prior to injection to the cardiac tissue engineering of MSC patch grafting. This study shows that MSCs have wide clinical applications in the treatment of AMI, suggesting improved myocardial tissue creation. A broader clinical application prospect will be explored and developed to improve the survival rate of MSC transplants and myocardial vascularization.

Objectives: Periodontal ligament stem cells (PDLSCs) are ideal seed cells for periodontal tissue regeneration. Our previous studies have indicated that the histone methyltransferase PRDM9 plays an important role in human periodontal ligament stem cells (hPDLSCs). Whether FBLN5, which is a downstream gene of PRDM9, also has a potential impact on hPDLSCs is still unclear.

Methods: Senescence was assessed using β-galactosidase and Enzyme-linked immunosorbent assay (ELISA). Osteogenic differentiation potential of hPDLSCs was measured through Alkaline phosphatase (ALP) activity assay and Alizarin red detection, while gene expression levels were evaluated using western blot and RT-qPCR analysis.

Results: FBLN5 overexpression promoted the osteogenic differentiation and senescence of hPDLSCs. FBLN5 knockdown inhibited the osteogenic differentiation and senescence of hPDLSCs. Knockdown of PRDM9 decreased the expression of FBLN5 in hPDLSCs and inhibited senescence of hPDLSCs. Additionally, both FBLN5 and PRDM9 promoted the expression of phosphorylated p38 MAPK, Erk1/2 and JNK. The p38 MAPK pathway inhibitor SB203580 and the Erk1/2 pathway inhibitor PD98059 have the same effects on inhibiting the osteogenic differentiation and senescence of hPDLSCs. The JNK pathway inhibitor SP600125 reduced the senescence of hPDLSCs.

Conclusion: FBLN5 promoted senescence and osteogenic differentiation of hPDLSCs via activation of the MAPK signaling pathway. FBLN5 was positively targeted by PRDM9, which also activated the MAPK signaling pathway.

Intervertebral disc degeneration (IVDD) is a serious condition that manifests as low back pain, intervertebral disc protrusion, and spinal canal stenosis. At present, the main treatment methods for IVDD are surgical interventions such as discectomy, total disc replacement, and spinal fusion. However, these interventions have shown limitations, such as recurrent lumbar disc herniation after discectomy, lesions in adjacent segments, and failure of fixation. To overcome these shortcomings, researchers have been exploring stem cell transplantation therapy, such as mesenchymal stem cell (MSC) transplantation, but the treatment results are still controversial. Therefore, researchers are in search of new methods that are more efficient and have better outcomes. The exosomes from stem cells contain a variety of bioactive molecules that mediate cell interactions, and these components have been investigated for their potential therapeutic role in the repair of various tissue injuries. Recent studies have shown that MSC-derived miRNAs in exosomes and vesicles have therapeutic effects on nucleus pulposus cells, annulus fibrosus, and cartilage endplate. miRNAs play a role in many cell activities, such as cell proliferation, apoptosis, and cytokine release, by acting on mRNA translation, and they may have immense therapeutic potential, especially when combined with stem cell therapy. This article reviews the current status of research on intervertebral disc repair, especially with regard to the latest research findings on the molecular biological mechanisms of miRNAs in MSC-derived exosomes in intervertebral disc repair.