Current Stem Cell Research & Therapy - Volume 19, Issue 10, 2024

Mesenchymal stem cells (MSCs) have been identified as potential therapeutics for various diseases. In contrast to other sources of MSCs, dental stem cells (DSCs) have received increased attention due to their high activity and easy accessibility. Among them, dental pulp stem cells (DPSCs) exhibit superior self-renewal, multipotency, immunomodulatory, and regenerative capacities. Following their inspiring performance in animal models and clinical trials, DPSCs show pharmacological potential in regenerative medicine. In this review, we have generalized the sources, heterogeneity, and biological characteristics of DPSCs, as well as compared them with other types of dental stem cells. In addition, we summarized the application of DPSCs in digestive diseases (such as liver, esophageal, and intestinal diseases), highlighting their regenerative and pharmacological potential based on the existing preclinical and clinical evidence. Specifically, DPSCs can be home to injured or inflamed tissues and exert repair and regeneration functions by facilitating immune regulation, anti-inflammation, and directional differentiation. Although DPSCs have a rosy prospect, future studies should handle the underlying drawbacks and pave the way for the identification of DPSCs as novel regenerative medicine.

In the last decade, liver diseases with high mortality rates have become one of the most important health problems in the world. Organ transplantation is currently considered the most effective treatment for compensatory liver failure. An increasing number of patients and shortage of donors has led to the attention of reconstructive medicine methods researchers. The biggest challenge in the development of drugs effective in chronic liver disease is the lack of a suitable preclinical model that can mimic the microenvironment of liver problems. Organoid technology is a rapidly evolving field that enables researchers to reconstruct, evaluate, and manipulate intricate biological processes in vitro. These systems provide a biomimetic model for studying the intercellular interactions necessary for proper organ function and architecture in vivo. Liver organoids, formed by the self-assembly of hepatocytes, are microtissues and can exhibit specific liver characteristics for a long time in vitro. Hepatic organoids are identified as an impressive tool for evaluating potential cures and modeling liver diseases. Modeling various liver diseases, including tumors, fibrosis, non-alcoholic fatty liver, etc., allows the study of the effects of various drugs on these diseases in personalized medicine. Here, we summarize the literature relating to the hepatic stem cell microenvironment and the formation of liver Organoids.

Cancer stem cells (CSCs) play an essential role in tumour progression and metastasis. Stem cell ability of self-renewal enables it to persist over time, thereby contributing to cancer relapse or recurrence and also resistance to current therapies. Therefore, targeting CSCs emerged as a promising strategy of cancer treatment. CSCs exhibit differentiation, self-renewal, and plasticity, they contribute to formation of malignant tumours, also favors, metastasis, heterogeneity, multidrug resistance, and radiation resistance. Coventional cancer treatments predominantly target cancer cells that are not CSCs, CSCs frequently survive, eventually leading to relapse. This article focuses on the development of novel therapeutic strategies that combine conventional treatments and CSC inhibitors to eradicate cancer cells and CSCs, for the better and permanent treatment. However, the diversity of CSCs is a significant obstacle in the development of CSC-targeted therapies, necessitating extensive research for a better understanding and exploration of therapeutic approaches. Future development of CSC-targeted therapies will rely heavily on overcoming this obstacle.

Parkinson's disease (PD) is a progressive neurodegenerative disease marked by comparatively focal dopaminergic neuron degeneration in the substantia nigra of the midbrain and dopamine loss in the striatum, which causes motor and non-motor symptoms. Currently, pharmacological therapy and deep brain stimulation (DBS) are the primary treatment modalities for PD in clinical practice. While these approaches offer temporary symptom control, they do not address the underlying neurodegenerative process, and complications often arise. Stem cell replacement therapy is anticipated to prevent further progression of the disease due to its regenerative capacity, and considering the cost of immunosuppression and the potential immune dysfunctions, autologous stem cell transplantation holds promise as a significant method against allogeneic one to treat Parkinson's disease. In this review, the safety concerns surrounding tumorigenicity and complications associated with transplantation are discussed, along with methods utilized to evaluate the efficacy of such procedures. Subsequently, we summarize the preclinical and clinical studies involving autologous stem cell transplantation for PD, and finally talk about the benefits of autologous stem cell transplantation against allogeneic transplants.

Diabetes is a complex metabolic disease with a high global prevalence. The health and quality of life of patients with diabetes are threatened by many complications, including diabetic foot ulcers, diabetic kidney diseases, diabetic retinopathy, and diabetic peripheral neuropathy. The application of mesenchymal stem/stromal cells (MSCs) in cell therapies has been recognized as a potential treatment for diabetes and its complications. MSCs were originally thought to exert biological effects exclusively by differentiating and replacing specific impaired cells. However, the paracrine function of factors secreted by MSCs may exert additional protective effects. MSCs secrete multiple compounds, including proteins, such as growth factors, chemokines, and other cytokines; nucleic acids, such as miRNAs; and lipids, extracellular vesicles (EVs), and exosomes (Exos). Collectively, these secreted compounds are called the MSC secretome, and usage of these chemicals in cell-free therapies may provide stronger effects with greater safety and convenience. Recent studies have demonstrated positive effects of the MSC secretome, including improved insulin sensitivity, reduced inflammation, decreased endoplasmic reticulum stress, enhanced M2 polarization of macrophages, and increased angiogenesis and autophagy; however, the mechanisms leading to these effects are not fully understood. This review summarizes the current research regarding the secretome derived from MSCs, including efforts to quantify effectiveness and uncover potential molecular mechanisms in the treatment of diabetes and related disorders. In addition, limitations and challenges are also discussed so as to facilitate applications of the MSC secretome as a cell-free therapy for diabetes and its complications.

Liver failure (LF) is serious liver damage caused by multiple factors, resulting in severe impairment or decompensation of liver synthesis, detoxification, metabolism, and biotransformation. The general prognosis of LF is poor with high mortality in non-transplant patients. The clinical treatments for LF are mainly internal medicine comprehensive care, artificial liver support system, and liver transplantation. However, none of the above treatment strategies can solve the problems of all liver failure patients and has its own limitations. Mesenchymal stem cells (MSCs) are a kind of stem cells with multidirectional differentiation potential and paracrine function, which play an important role in immune regulation and tissue regeneration. In recent years, MSCs have shown multiple advantages in the treatment of LF in pre-clinical experiments and clinical trials. In this work, we reviewed the biological characteristics of MSCs, the possible molecular mechanisms of MSCs in the treatment of liver failure, animal experiments, and clinical application, and also discussed the existing problems of MSCs in the treatment of liver failure.

Background: Acute kidney injury (AKI) is characterized by inflammatory infiltration and damage and death of renal tubular epithelial cells (RTECs), in which hypoxia plays an important role. Deferoxamine (DFO) is a well-accepted chemical hypoxia-mimetic agent. Mesenchymal stem cell-conditioned medium (MSC-CM) can reduce local inflammation and repair tissue. In this study, we explored the effect and molecular mechanism of MSC-CM-mediated protection of RTECs under DFO-induced hypoxia. Methods: Rat renal proximal tubule NRK-52E cells were treated with different concentrations of DFO for 24 hours, followed by evaluation of RTEC injury, using a Cell Counting Kit-8 (CCK-8) to detect cell viability and western blotting to evaluate the expression of transforming growth factor- beta 1 (TGF-β1), α-smooth muscle actin (α-SMA), and hypoxia-inducible factor-1 alpha (HIF-1α) in NRK-52E cells. Then, three groups of NRK-52E cells were used in experiments, including normal control (NC), 25 μM DFO, and 25 μM DFO + MSC-CM. MSC-CM was obtained from the human umbilical cord. MSC-CM was used to culture cells for 12 hours before DFO treatment, then fresh MSC-CM and 25 μM DFO were added, and cells were cultured for another 24 hours before analysis. Results: Western blotting and cellular immunofluorescence staining showed culture of NRK-52E cells in 25 μM DFO for 24 hours induced HIF-1α and nuclear receptor coactivator-1 (NCoA-1), simulating hypoxia. MSC-CM could inhibit the DFO-induced up-regulation of α-SMA, TGF-β1, HIF-1α and NCoA-1. Conclusion: Our results suggest that MSC-CM has a protective effect on RTECs by down-regulating HIF-1α and NCoA-1, which may be the harmful factors in renal injury.

Objective: The aim of this study was to construct a multicompartment synchronous rotating bioreactor (MCSRB) for batch-production of homogenized adipose-derived stem cell (ADSC) microspheres and treat neurogenic erectile dysfunction (ED). Methods: Firstly, an MCSRB was constructed using a centrifugal device and hinged trays. Secondly, influence factors (density, rotational speed) on the formation of ADSC-spheroids were explored. Finally, a neurogenic ED model was established to verify the effectiveness and safety of ADSC-spheroids for ED treatment. Results: An MCSRB promoted ADSCs to gather microspheres, most of which were 90-130 μm in diameter. Supernatant from three-dimensional culture led to a significant increase in cytokine expression in ADSCs and migration rate in human umbilical vein endothelial cells (HUVECs) compared to control groups. The erectile function and pathological changes of the penis were improved in the ADSC-spheroids treatment group compared to the traditional ADSCs treatment group (p < 0.01). Conclusion: Efficient, batch, controlled and homogenized production of ADSC stem cell microspheres, and effective improvement of erectile dysfunction in neurogenic rats can be achieved using the MCSRB device.

Background: Aging is a biological and gradual deterioration of function in living organisms. Aging is one of the risk factors for heart disease. Objective: Although mesenchymal stem cell transplantation shows potential in heart disease treatment, the relationship between stem cell-based therapy and oxidative stress/inflammasome axis regulation remains unclear. This study hypothesized that intervention of stem cells showed protective effect on heart aging induced by D-galactose through regulation of oxidative stress/inflammasome axis. Methods: An aging animal model was designed to test the above hypothesis. Experimental animals were divided into three groups, including Sham, D-gal (aging rats induced by d-galactose), and D-gal+WJSC (aging rats receiving mesenchymal stem cells). Results: Compared to the Sham, the experimental results indicate that structural alteration (HE stain and Masson’s Trichrome stain), oxidative stress elevation (increase of TBARS level, expression of gp-91 and suppression of Sirt-1 as well as SOD2), increase of aging marker p53, suppression of cardiogenesis marker Troponin T, and inflammasome related protein markers expression (NLRP3, caspase-1 and IL-1 beta) were significantly observed in D-gal. In contrast, all pathological pathways were significantly improved in D-gal+WJSC when compared to D-gal. In addition, migration of stem cells to aging heart tissues was observed in the D-gal+WJSC group. Conclusion: These findings suggest that mesenchymal stem cell transplantation effectively ameliorates aging hearts through oxidative stress/inflammasome axis regulation. The results from this study provide clinical potential for stem cell-based therapy in the treatment of aging hearts.

Background: A reduced effective local concentration significantly contributes to the unsatisfactory therapeutic results of epirubicin in gastric cancer. Mesenchymal stem cells exhibit targeted chemotaxis towards solid tumors and form tunneling nanotubes with tumor cells, facilitating the delivery of various substances. This study demonstrates the novelty of mesenchymal stem cells in releasing epirubicin into gastric cancer cells through tunneling nanotubes. Objective: Epirubicin delivery to gastric cancer cells using mesenchymal stem cells. Methods: In vitro transwell migration assays, live cell tracking, and in vivo targeting assays were used to demonstrate the chemotaxis of mesenchymal stem cells towards gastric cancer. We verified the targeted chemotaxis of mesenchymal stem cells towards gastric cancer cells and the epirubicin loading ability using a high-content imaging system (Equipment type:Operetta CLS). Additionally, tunneling nanotube formation and the targeted release of epirubicin-loaded mesenchymal stem cells co-cultured with gastric cancer cells through mesenchymal stem cell-tunneling nanotubes into gastric cancer cells was observed using Operetta CLS. Results: Mesenchymal stem cells demonstrated targeted chemotaxis towards gastric cancer, with effective epirubicin loading and tolerance. Co-culturing induced tunneling nanotube formation between these cells. Epirubicin-loaded mesenchymal stem cells were released into gastric cancer cells through tunneling nanotubes, significantly increasing their non-viability compared to the negative control group (p < 0.05). Conclusions: We identified a novel approach for precisely targeting epirubicin release in gastric cancer cells. Therefore, mesenchymal stem cell-tunneling nanotubes could serve as a potential tool for targeted delivery of drugs, enhancing their chemotherapeutic effects in cancer cells.