Application Of Stem Cell Therapy Research Articles

Enhancement of the function of mesenchymal stem cells by using a GMP-grade three-dimensional hypoxic large-scale production system

BackgroundEfficiently increasing the production of clinical-grade mesenchymal stem cells (MSCs) is crucial for clinical applications. Challenges with the current planar culture methods include scalability issues, labour intensity, concerns related to cell senescence, and heterogeneous responses. This study aimed to establish a large-scale production system for MSC generation. In addition, a comparative analysis of the biological differences between MSCs cultured under various conditions was conducted. Methods and materialsWe developed a GMP-grade three-dimensional hypoxic large-scale production (TDHLSP) system for MSCs using self-fabricated glass microcarriers and a multifunctional bioreactor. Different parameters, including cell viability, cell diameter, immunophenotype, morphology, karyotype, and tumourigenicity were assessed in MSCs cultured using different methods. Single-cell RNA sequencing (scRNA-seq) revealed pathways and genes associated with the enhanced functionality of MSCs cultured in three dimensions under hypoxic conditions (3D_Hypo MSCs). Moreover, CD142 knockdown in 3D_Hypo MSCs confirmed its in vitro functions. ResultsInoculating 2 × 108 MSCs into a 2.6 L bioreactor in the TDHLSP system resulted in a final scale of 4.6 × 109 3D_Hypo MSCs by day 10. The 3D_Hypo MSCs retained characteristics of the 2D MSCs, demonstrating their genomic stability and non-tumourigenicity. Interestingly, the subpopulations of 3D_Hypo MSCs exhibited a more uniform distribution and a closer relationship than those of 2D MSCs. The heterogeneity of MSCs was strongly correlated with ‘cell cycle’ and ‘stroma/mesenchyme’, with 3D_Hypo MSCs expressing higher levels of activated stroma genes. Compared to 2D MSCs, 3D_Hypo MSCs demonstrated enhanced capabilities in blood vessel formation, TGF-β1 secretion, and inhibition of BV2 proliferation, with maintenance of Senescence-Associated β-Galactosidase (SA-β-gal) negativity. However, the enhanced functions of 3D_Hypo MSCs decreased upon the downregulation of CD142 expression. ConclusionThe TDHLSP system led to a high overall production of MSCs and promoted uniform distribution of MSC clusters. This cultivation method also enhanced key cellular properties, such as angiogenesis, immunosuppression, and anti-aging. These functionally improved and uniform MSC subpopulations provide a solid basis for the clinical application of stem cell therapies.

Leveraging stem cells to combat hepatitis: a comprehensive review of recent studies.

Hepatitis is a significant global public health concern, with viral infections being the most common cause of liver inflammation. Antiviral medications are the primary treatments used to suppress the virus and prevent liver damage. However, the high cost of these drugs and the lack of awareness and stigma surrounding the disease create challenges in managing hepatitis. Stem cell therapy has arisen as a promising therapeutic strategy for hepatitis by virtue of its regenerative and immunomodulatory characteristics. Stem cells have the exceptional capacity to develop into numerous cell types and facilitate tissue regeneration, rendering them a highly promising therapeutic avenue for hepatitis. In animal models, stem cell therapy has demonstrated worthy results by reducing liver inflammation and improving liver function. Furthermore, clinical trials have been undertaken to assess the safety and effectiveness of stem cell therapy in individuals with hepatitis. This review aims to explore the involvement of stem cells in treating hepatitis and highlight the findings from studies conducted on both animals and humans. The objective of this review is to primarily concentrate on the ongoing and future clinical trials that assess the application of stem cell therapy in the context of hepatitis, including the transplantation of autologous bone marrow-derived stem cells, human induced pluripotent stem cells, and other mesenchymal stem cells. In addition, this review will explore the potential merits and constraints linked to stem cell therapy for hepatitis, as well as its prospective implications in the management of this disease.

Stem cell therapy for degenerative disc disease: Bridging the gap between preclinical promise and clinical potential.

Stem cell therapy has gained attention in the field of regenerative medicine due to its potential to restore damaged tissue. This article focuses on the application of stem cell therapy for treating spinal pathologies, particularly intervertebral disc degeneration. Disc degeneration is a major cause of low back pain and is characterized by changes in the matrix and inflammation. Animal studies have demonstrated that the implantation of mesenchymal stem cells (MSCs) yields promising results, including increased disc height, improved hydration, and reduced inflammation. However, the number of clinical trials remains limited, necessitating further research to optimize MSCs therapy. Although preclinical studies offer valuable insights, caution is needed when extrapolating these findings to clinical practice. Stem cell therapy still faces multiple challenges, such as the durability and survival of MSCs upon implantation, uncertain pathways to discogenic differentiation, and the adverse impact of a harsh microenvironment on cell survival. The avascular nature of the intervertebral disc and dynamic loading conditions also affect the adaptation of transplanted cells. Despite these obstacles, stem cell therapy holds promise as a potential treatment for disc degeneration, and ongoing research aims to fill the current gap in conclusive data.

Molecular mechanism underlying miR-204-5p regulation of adipose-derived stem cells differentiation into cells from three germ layers

The limited differentiation ability of adipose-derived stem cells (ADSCs) limits their application in stem cell therapy and regenerative medicine. Here, we explore the molecular mechanism by which miR-204-5p regulates ADSCs differentiation into cells derived from the three germ layers (i.e., adipocytes, neurocytes, and hepatocytes). Although miR-204-5p overexpression inhibited ADSCs differentiation into adipocytes, neurocyte and hepatocyte differentiation were promoted. Mechanistically, miR-204-5p inhibited the expression of PPARG by regulating the AMPK signaling pathway, thereby inhibiting ADSCs differentiation into adipocytes. Further, miR-204-5p regulated JAG1/NOTCH3 axis for the inhibition of differentiation into adipocytes and promotion of differentiation into neurocytes. miR-204-5p might also promote ADSCs differentiation into hepatocytes by upregulating E2F8. The findings of this study provide novel insights into the regulatory mechanisms underlying early embryonic development and will help to facilitate the application of ADSCs in stem cell therapy and regenerative medicine.

A large-scale production of mesenchymal stem cells and their exosomes for an efficient treatment against lung inflammation.

Mesenchymal stem cells (MSCs) and their produced exosomeshave demonstrated inherent capabilities of inflammation-guided targeting and inflammatory modulation, inspiring their potential applications as biologic agents for inflammatory treatments. However, the clinical applications of stem cell therapies are currently restricted by several challenges, and one of them is the mass production of stem cells to satisfy the therapeutic demands in the clinical bench. Herein, a production of human amnion-derived MSCs (hMSCs) at a scale of over 1 × 109 cells per batch was reported using a three-dimensional (3D)culture technology based on microcarriers coupled with a spinner bioreactor system. The present study revealed that this large-scale production technology improved the inflammation-guided migration and the inflammatory suppression of hMSCs, without altering their major properties as stem cells. Moreover, these large-scale produced hMSCs showed an efficient treatment against the lipopolysaccharide (LPS)-induced lung inflammation in mice models. Notably, exosomes collected from these large-scale produced hMSCs were observed to inherit the efficient inflammatory suppression capability of hMSCs. The present study showed that 3D culture technology using microcarriers coupled with a spinner bioreactor system can be a promising strategy for the large-scale expansion of hMSCs with improved anti-inflammation capability, as well as their secreted exosomes.

Stem Cell Therapy for Liver Diseases: Current Perspectives.

Stem cell therapy offers a promising avenue for advanced liver disease cases as an alternative to liver transplantation. Clinical studies are underway to explore the potential of stem cells from various sources in treating different liver diseases. However, due to the variability among current studies, further validation is needed to ensure the safety and effectiveness of stem cell therapy. To establish a strong foundation for optimal stem cell therapy applications, selection of suitable stem cell sources, standardization of transplantation protocols, and patient criteria are vital. This review comprehensively examines existing literature on stem cell sources, transplantation methods, and patient selection. Additionally, we discuss novel strategies, including stem cell preconditioning, cell-free therapy, genetic modification of stem cells, and the use of liver organoids, addressing the limitations of current stem cell therapies. Nevertheless, these innovative approaches require further validation.

The mechanism of adipose mesenchymal stem cells to stabilize the immune microenvironment of pelvic floor injury by regulating pyroptosis and promoting tissue repair

Pelvic organ prolapse (POP) has a high incidence rate among Chinese women. Repeated mechanical stimulation is an important factor causing POP, but the injury mechanism has not yet been elucidated. The purpose of this study is to explore the related mechanisms of pelvic floor supporting tissue damage caused by mechanical force and the application of stem cell therapy. First, we obtained vaginal wall and sacral ligament tissue samples from clinical patients for examination. Pelvic floor support tissues of POP patients displayed high expression of inflammation and immune disorders. Then, we constructed a rat model of childbirth injury. In vivo and in vitro experiments investigated the key mechanism of pelvic floor support tissue injury caused by mechanical force. We discovered that after mechanical force, a large number of reactive oxygen species (ROS) and macrophages rapidly accumulated in pelvic floor tissues. ROS stimulated macrophages to produce NLRP3 inflammatory complex, induced the release of interleukin (IL-1β) and pyroptosis and exacerbated the inflammatory state of damaged tissues, persisting chronic inflammation of fibroblasts in supporting tissues, thus causing the pelvic floor's extracellular matrix (ECM) collagen metabolic disorder. Resultingly impeding the repair process, thereby causing the onset and progression of the disease. Through their paracrine ability, we discovered that adipose mesenchymal stem cells (ADSCs) could inhibit this series of pathological processes and promote tissue repair, asserting a good therapeutic effect. Simultaneously, to overcome the low cell survival rate and poor therapeutic effect of directly injecting cells, we developed a ROS-responsive PVA@COLI hydrogel with ADSCs. The ROS-scavenging properties of the gel could reshape the site of inflammation injury, enhance cell survival, and play a role in subsequent treatment. The findings of this study could serve as a basis for early, targeted intervention therapy for POP and representing a promising approach.

Current Status and Progress in Stem Cell Therapy for Intracerebral Hemorrhage.

Intracerebral hemorrhage is a highly prevalent and prognostically poor disease, imposing immeasurable harm on human life and health. However, the treatment options for intracerebral hemorrhage are severely limited, particularly in terms of improving the microenvironment of the lesion, promoting neuronal cell survival, and enhancing neural function. This review comprehensively discussed the application of stem cell therapy for intracerebral hemorrhage, providing a systematic summary of its developmental history, types of transplants, transplantation routes, and transplantation timing. Moreover, this review presented the latest research progress in enhancing the efficacy of stem cell transplantation, including pretransplantation preconditioning, genetic modification, combined therapy, and other diverse strategies. Furthermore, this review pioneeringly elaborated on the barriers to clinical translation for stem cell therapy. These discussions were of significant importance for promoting stem cell therapy for intracerebral hemorrhage, facilitating its clinical translation, and improving patient prognosis.

CREB3L2 Regulates Hemidesmosome Formation during Epithelial Sealing.

The long-term success rate of dental implants can be improved by establishing a favorable biological sealing with a high-quality epithelial attachment. The application of mesenchymal stem cells (MSCs) holds promise for facilitating the soft tissue integration around implants, but the molecular mechanism is still unclear and the general application of MSC sheet for soft tissue integration is also relatively unexplored. We found that gingival tissue-derived MSC (GMSC) sheet treatment significantly promoted the expression of hemidesmosome (HD)-related genes and proteins in gingival epithelial cells (GECs). The formation of HDs played a key role in strengthening peri-implant epithelium (PIE) sealing. Further, high-throughput transcriptome sequencing showed that GMSC sheet significantly upregulated the PI3K/AKT pathway, confirming that cell adhesion and HD expression in GECs were regulated by GMSC sheet. We observed that the expression of transcription factor CREB3L2 in GECs was downregulated. After treatment with PI3K pathway inhibitor LY294002, CREB3L2 messenger RNA and protein expression levels were upregulated. Further experiments showed that overexpression or knockdown of CREB3L2 could significantly inhibit or promote HD-related genes and proteins, respectively. We confirmed that CREB3L2 was a transcription factor downstream of the PI3K/AKT pathway and participated in the formation of HDs regulated by GMSC sheet. Finally, through the establishment of early implant placement model in rats, we clarified the molecular function of CREB3L2 in PIE sealing as a mechanical transmission molecule in GECs. The application of GMSC sheet-implant complex could enhance the formation of HDs at the implant-PIE interface and decrease the penetration distance of horseradish peroxidase between the implant and PIE. Meanwhile, GMSC sheet reduced the length of CREB3L2 protein expression on PIE. These findings elucidate the potential function and molecular mechanism of MSC sheet regulating the epithelial sealing around implants, providing new insights and ideas for the application of stem cell therapy in regenerative medicine.

The Application of Stem Cell Therapy on Type 1 Diabetes

Type 1 diabetes (T1D) is also known as insulin-dependent diabetes caused by autoimmune reactions in the patient's body. T1D is caused by the destruction of the pancreatic β cells of the patient by their immune system in the case of autoimmunity. It can lead to dehydration, frequent urination, potential damage to many organs in the body etc. If left untreated, it can lead to death. Consequently, research groups have invested a huge effort to develop possible treatments for. Currently, the existing solutions for T1D mainly include insulin therapy and immunotherapy, but the high costs of insulin therapy and the adverse reactions associated with immunotherapy limits the efficacy of these treatments and are therefore imperfect. To this day, there is no permanent cure for T1D, many study groups have proved that stem cell therapy could provide a possible solution because of its success in curing other diseases. Stem cell therapy is a treatment in which pluripotent of multipotent cells are transplanted into a patient's body in a certain way to restore normal function. The capacity do differentiate into different cell types can help stem cells stop the process of β cell destructionz, preserve remaining beta cell blocks, and promote the regeneration of primary beta cells. This review provided an overview of the existing therapies available to treat T1D, gathered information from previous clinical trials and emphasized the importance of stem cell therapies based on the current state of art.

Effect of size and morphology of functionalized upconversion nanoparticle labeled probe on stem cell absorption.

In order to improve the application of stem cell therapy, it is important to monitor the proliferation and differentiation of transplanted stem cells in real time, high sensitivity and high precision. Upconversion nanoparticles (UCNPs) have been employed as bioimaging agents and delivery vehicles for gene therapeutics in several types of cells. Herein, we fabricated multiple functional upconversion nanoparticles (FUC-NPs) as exogenous contrast agents to investigate the effect of FUC-NPs size on the efficiency of tracking human umbilical cord mesenchymal stem cells (HUCMSCs). We used TEM, DLS, MTT, etc. systematically detected the effects of nanoparticle dose and exposure time on HUCMSCs cytotoxicity. Our data showed that incubation of FUC-NPs, HUCMSCs are able to maintain their viability and differentiation ability. Interestingly, the small size FUC-NPs examined, S-FUCs, had a much higher uptake capability than the other FUC-NPs (B-FUCs, H-FUCs and R-FUCs).The study will aid in UCNPs for the engineering of stem cell application in the future.

Efficacy and Potential of Stem Cell Therapy for Alzheimer’s Disease

Alzheimer’s Disease (AD) is characterized primarily by the buildup of beta-amyloid plaques and tau proteins. It is a very common neurodegenerative disease that is marked by cognitive decline, neuronal and synaptic loss. AD pathology is not fully understood and there is currently no cure. The disease is terminal and devastates the lives of many. Stem cell therapy involves the use of stem cell’s properties of regeneration and repair to reverse the damage of many diseases. The application of stem cell therapy to AD seems to have the promise to mitigate and reverse the onset of AD. Animal models have displayed the effectiveness of stem cell therapy towards AD by improving cognitive performance and promoting neurogenesis. The abilities and applications of stem cell therapy seem to be highly promising despite having bottlenecks. The difficulties in controlling differentiation due to complexities in controlling the process is the primary issue presented. With the use of stem cell therapy for AD, it is also possible to adapt the technology to various other neurodegenerative diseases and various diseases overall.

Role of stem cells in aortic aneurysm

In recent years, aortic aneurysms (AAs) have attracted increasing attention due to their asymptomatic onset and high mortality. In clinic, surgery and anti-hypertensive or lipid-lowering medicine is usually applied in the treatments of AA. However, AA is prone to relapse and sudden rupture may happen. Therefore, more effective prevention and treatment methods are urgently needed. Stem cells are believed to play a crucial role in vascular formation and regeneration of damaged tissues during vascular disease progression. With the development of single-cell RNA sequencing analysis, many populations of stem cells have been discovered in AA tissues. Recent studies have demonstrated that they may participate in the occurrence or development of AAs. Besides, there is a prospect in clinical treatment for AAs when regenerative medicine with stem cells comes into the picture. This review mainly discusses the latest findings on the crucial roles of stem cells in AAs as well as their potential therapeutic strategies of stem cells, which provides some references for the prevention, diagnosis, and treatment of AAs. Further studies are needed to explore the novel application of stem cell therapies for AAs.

Stem cell therapy: An emerging hope in regenerative medicine

In recent years, a new revolutionary giant has developed which gives high hopes, promises and proficient scientific study area is Stem cell therapy. Recent research showing the effective application of stem cell therapies to patients has enriched the hope that such regeneration methods may one day become a remedy for a variety of difficult ailments. In the past few years, clinical trials in which stem cell therapies are involved have raised pretty exponentially. Some of these trials had a notable influence on a number of ailments, such as neurological disorders, pulmonary dysfunctions, diseases related to metabolism and the endocrine system, disorders of reproduction, skin burns, and cardiovascular conditions. Although mesenchymal stem cells (MSCs) have been put to use clinically to treat autoimmune and chronic inflammatory illnesses, concerns about the field of regenerative medicine remain due to their ability to endorse cancer growth and metastasis as well as their overstated therapeutic potential. The most significant obstacle to the development of hESC-based therapeutic medicines is an ethical quandary involving the killing of a human embryo. Induced pluripotent stem cells (iPSCs), which were first developed to address this problem, have since been proven to be effective, although there are still lingering concerns regarding their efficacy for use in medicine. The unwanted differentiation and cancerous transformation are significant safety concerns, iPSCs can be employed for human reproductive cloning, however, their limitless differentiation efficiency raises concerns about the possibility of producing genetically altered human embryos and human-animal chimeras. The issue is contentious because some people claim it goes against nature, yet nature herself gives an opportunity that opens a new avenue for people who suffer from untreated ailments and disorders.

Human Umbilical Cord Mesenchymal Stem Cells Improve the Status of Hypoxic/Ischemic Cerebral Palsy Rats by Downregulating NogoA/NgR/Rho Pathway.

Human umbilical cord mesenchymal stem cells (hUCMSC) have shown promising potential in ameliorating brain injury, but the mechanism is unclear. We explore the role of NogoA/NgR/Rho pathway in mediating hUCMSC to improve neurobehavioral status and alleviate brain injury in hypoxia/ischemia-induced CP (cerebral palsy) rat model in order to promote the clinical application of stem cell therapy in CP. The injury model of HT22 cells was established after 3 h hypoxia, and then co-cultured with hUCMSC. The rat model of CP was established by ligation of the left common carotid artery for 2.5 h. Subsequently, hUCMSC was administered via the tail vein once a week for a total of four times. The neurobehavioral status of CP rats was determined by behavioral experiment, and the pathological brain injury was determined by pathological staining method. The mRNA and protein expressions of NogoA, NgR, RhoA, Rac1, and CDC42 in brain tissues of rats in all groups and cell groups were detected by real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunofluorescence. The CP rats exhibited obvious motor function abnormalities and pathological damage. Compared with the control group, hUCMSC transplantation could significantly improve the neurobehavioral situation and attenuate brain pathological injury in CP rats. The relative expression of NogoA, NgR, RhoA mRNA, and protein in brain tissues of rats in the CP group was significantly higher than the rats in the sham and CP+hUCMSC group. The relative expression of Rac1, CDC42 mRNA, and protein in brain tissues of rats in the CP group was significantly lower than the rats in the sham and CP+hUCMSC group. The animal experiment results were consistent with the experimental trend of hypoxic injury of HT22 cells. This study confirmed that hUCMSC can efficiently improve neurobehavioral status and alleviate brain injury in hypoxia/ischemia-induced CP rat model and HT22 cell model through downregulating the NogoA/NgR/Rho pathway.

Treating peripheral nerve injury-induced spinal cord degeneration and neuropathic pain with peripherally administrated stem cells.

Treating peripheral nerve injury-induced spinal cord degeneration and neuropathic pain with peripherally administrated stem cells.

Mesenchymal stem cell therapy for wound healing: An update to 2022

The skin is an organ that performs complex functions of both the innate and adaptive immune systems. It serves as the first physical barrier to protect the body from environmental factors. Skin also carries aesthetic value in people's desire for eternal youth. Skin lesions are often unwanted, causing open wounds that can be contagious or permit infection of the body, scars, skin aging, and loss of skin function, with long-term psychological consequences. The application of stem cell therapy based on mesenchymal stem cells (MSCs) is constantly developing in the field of skin regeneration, which is highly regarded as a therapy for patients suffering skin lesions from burns, deep wounds, cosmetic surgery, or genetic diseases. MSC therapy has shed light on groundbreaking treatments in immune, anti-inflammatory, and regenerative medicine, including for skin diseases. Additionally, the development of stem cells seems to limit skin aging. It is gradually becoming an integral technique at hospitals as a regular therapy for illness, as well as a cosmetic intervention. This review seeks to introduce the skin system and its related disorders; highlight the common characteristics and mechanisms of MSCs; and analyze updated clinical applications and experiments to date in MSC therapy for regenerative biomedicine and skin diseases.

Mesenchymal stem cells to treat female infertility; future perspective and challenges: A review.

Infertility negatively impacts the overall health and social life of affected individuals and couples. Female infertility is their inability to perceive pregnancy. To date, polycystic ovary syndrome, primary ovarian insufficiency, fallopian tube obstruction, endometriosis, and intrauterine synechiae have been identified as the primary causes of infertility in women. However, despite the mutual efforts of clinicians and research scientists, the development of an effective treatment modality has met little success in combating female infertility. Intriguingly, significant research has demonstrated mesenchymal stem cells as an optimal source for treating infertility disorders. Therefore, here we attempted to capsulize to date available studies to summarize the therapeutic potential of mesenchymal stem cells in combating infertility in women by focusing on the underlying mechanism through which stem cells can reduce the effects of ovarian disorders. Furthermore, we also discussed the preclinical and clinical application of stem cell therapy, their limitation, and the future perspective to minimize these limitations.

Application of Stem Cell Therapy During the Treatment of HIV/AIDS and Duchenne Muscular Dystrophy.

Treating diseases such as Muscular Dystrophy (MD) and HIV/AIDS pose several challenges to the rapidly evolving field of regenerative medicine. Previously, stem cell therapy has been said to affect the clinical courses of HIV/AIDS and MD, but, in practice, eradication or control of these diseases was not achievable. The introduction of gene editing into stem cell therapy has stimulated HIV/AIDS and MD cell therapy research studies substantially. Here, we review current methods of treating HIV/AIDS and MD using stem cell therapy. This review also details the use of different types of cells and methods in cell therapy and the modeling of new cell-based therapies to treat Duchenne muscular dystrophy. We speculate that the effective use of stem cell therapy in conjunction with other treatment therapies , such as steroids and rehabilitation , could improve livelihood.

Modulating myoblast differentiation with RNA-based controllers.

Tunable genetic controllers play a critical role in the engineering of biological systems that respond to environmental and cellular signals. RNA devices, a class of engineered RNA-based controllers, enable tunable gene expression control of target genes in response to molecular effectors. RNA devices have been demonstrated in a number of systems showing proof-of-concept of applying ligand-responsive control over therapeutic activities, including regulation of cell fate decisions such as T cell proliferation and apoptosis. Here, we describe the application of a theophylline-responsive RNA device in a muscle progenitor cell system to control myogenic differentiation. Ribozyme-based RNA switches responsive to theophylline control fluorescent reporter expression in C2C12 myoblasts in a ligand dependent manner. HRAS and JAK1, both anti-differentiation proteins, were incorporated into RNA devices. Finally, we demonstrate that the regulation of HRAS expression via theophylline-responsive RNA devices results in the modulation of myoblast differentiation in a theophylline-dependent manner. Our work highlights the potential for RNA devices to exert drug-responsive, tunable control over cell fate decisions with applications in stem cell therapy and basic stem cell biology research.