Cardioprotective effects of fetal kidney-derived mesenchymal stem cells on doxorubicin-induced cardiotoxicity in rats

Cardiotoxicity is one of the most common side effects of doxorubicin (DOX), a chemotherapy drug used in the treatment of many carcinomas. In recent years, stem-cell therapies have been successfully used to prevent cardiotoxicity. This study investigated the efficacy of intraperitoneally administered fetal kidney-derived mesenchymal stem cells (FKD-MSCs) in preventing DOX-induced cardiotoxicity in rats. For this purpose, thirty rats were randomly divided into three groups: control, DOX and mesenchymal stem cell (MSC) groups. Adriamycin was injected as a single dose via the tail vein in the DOX and MSC groups in order to induce cardiotoxicity. FKD-MSC was applied to the MSC group by the intraperitoneal route after cardiotoxicity had been established. Then the rats were euthanized, and routine histological procedures were performed on their hearts. H&E and Masson’s stains were used for histopathology. Cardiac Troponin-T and I (cTnT, cTnI), Caspase-3 and BCL-XL antibodies were used for immunohistochemistry. Vacuoles, edema, degeneration and necrosis were observed histopathologically mostly in the DOX group. Lesions in the control and MSC groups were less severe. Fibrosis in the control and MSC groups was milder. cTnT and cTnI immunopositive staining was most commonly seen in the control group, followed by the MSC group. Immunohistochemical staining by Caspase-3 and BCL-XL showed that their expressions in the MSC group were statistically similar to those in the control group. Accordingly, it was concluded that the intraperitoneal application of MSC had a positive effect on histopathological findings, fibrosis, immunohistochemistry, especially apoptosis, neovascularization, and anti-apoptotic development, whereas troponin levels were not found to be therapeutic.

Stem Cell-based Therapeutic and Diagnostic Approaches in Alzheimer's Disease

Background: Alzheimer’s disease (AD) is a neurodegenerative impairment mainly recognized by memory loss and cognitive deficits. However, the current therapies against AD are mostly limited to palliative medications, prompting researchers to investigate more efficient therapeutic approaches for AD, such as stem cell therapy. Recent evidence has proposed that extensive neuronal and synaptic loss and altered adult neurogenesis, which is perceived pivotal in terms of plasticity and network maintenance, occurs early in the course of AD, which exacerbates neuronal vulnerability to AD. Thus, regeneration and replenishing the depleted neuronal networks by strengthening the endogenous repair mechanisms or exogenous stem cells and their cargoes is a rational therapeutic approach. Currently, several stem cell-based therapies as well as stem cell products like exosomes, have shown promising results in the early diagnosis of AD. Objective: This review begins with a comparison between AD and normal aging pathophysiology and a discussion on open questions in the field. Next, summarizing the current stem cell-based therapeutic and diagnostic approaches, we declare the advantages and disadvantages of each method. Also, we comprehensively evaluate the human clinical trials of stem cell therapies for AD. Methodology: Peer-reviewed reports were extracted through Embase, PubMed, and Google Scholar until 2021. Results: With several ongoing clinical trials, stem cells and their derivatives (e.g., exosomes) are an emerging and encouraging field in diagnosing and treating neurodegenerative diseases. Although stem cell therapies have been successful in animal models, numerous clinical trials in AD patients have yielded unpromising results, which we will further discuss.

Recent advances of biomaterials in stem cell therapies

Stem cells have been utilized as ''living drugs'' in clinics for decades. Their self-renewal, differentiation, and immunomodulating properties provide potential solutions for a variety of malignant diseases and disorders. However, the pathological environment may diminish the therapeutic functions and survival of the transplanted stem cells, causing failure in clinical translation. To overcome these challenges, researchers have developed biomaterial-based strategies that facilitate in vivo tracking, functional engineering, and protective delivery of stem cells, paving the way for next-generation stem cell therapies. In this perspective, we briefly overview different types of stem cells and the major clinical challenges and summarize recent progress of biomaterials applied to boost stem cell therapies.

Targeting Programmed Cell Death to Improve Stem Cell Therapy: Implications for Treating Diabetes and Diabetes-Related Diseases

Stem cell therapies have shown promising therapeutic effects in restoring damaged tissue and promoting functional repair in a wide range of human diseases. Generations of insulin-producing cells and pancreatic progenitors from stem cells are potential therapeutic methods for treating diabetes and diabetes-related diseases. However, accumulated evidence has demonstrated that multiple types of programmed cell death (PCD) existed in stem cells post-transplantation and compromise their therapeutic efficiency, including apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis. Understanding the molecular mechanisms in PCD during stem cell transplantation and targeting cell death signaling pathways are vital to successful stem cell therapies. In this review, we highlight the research advances in PCD mechanisms that guide the development of multiple strategies to prevent the loss of stem cells and discuss promising implications for improving stem cell therapy in diabetes and diabetes-related diseases.

Current progress of rehabilitative strategies in stem cell therapy for spinal cord injury: a review

Stem cell-based regenerative therapy has opened an avenue for functional recovery of patients with spinal cord injury (SCI). Regenerative rehabilitation is attracting wide attention owing to its synergistic effects, feasibility, non-invasiveness, and diverse and systemic properties. In this review article, we summarize the features of rehabilitation, describe the mechanism of combinatorial treatment, and discuss regenerative rehabilitation in the context of SCI. Although conventional rehabilitative methods have commonly been implemented alone, especially in studies of acute-to-subacute SCI, the combinatorial effects of intensive and advanced methods, including various neurorehabilitative approaches, have also been reported. Separating the concept of combined rehabilitation from regenerative rehabilitation, we suggest that the main roles of regenerative rehabilitation can be categorized as conditioning/reconditioning, functional training, and physical exercise, all of which are indispensable for enhancing functional recovery achieved using stem cell therapies.

Cell-derived extracellular vesicles and membranes for tissue repair

Humans have a limited postinjury regenerative ability. Therefore, cell-derived biomaterials have long been utilized for tissue repair. Cells with multipotent differentiation potential, such as stem cells, have been administered to patients for the treatment of various diseases. Researchers expected that these cells would mediate tissue repair and regeneration through their multipotency. However, increasing evidence has suggested that in most stem cell therapies, the paracrine effect but not cell differentiation or regeneration is the major driving force of tissue repair. Additionally, ethical and safety problems have limited the application of stem cell therapies. Therefore, nonliving cell-derived techniques such as extracellular vesicle (EV) therapy and cell membrane-based therapy to fulfil the unmet demand for tissue repair are important. Nonliving cell-derived biomaterials are safer and more controllable, and their efficacy is easier to enhance through bioengineering approaches. Here, we described the development and evolution from cell therapy to EV therapy and cell membrane-based therapy for tissue repair. Furthermore, the latest advances in nonliving cell-derived therapies empowered by advanced engineering techniques are emphatically reviewed, and their potential and challenges in the future are discussed. Graphical Abstract

Stem cell clinics in the UK: a web-based study

Aim: Explore the nature and extent of web-based promotion of stem cell treatments marketed by clinics in the UK. Materials & methods: Web-based analysis of clinics in the UK using predefined variables, with analysis of eligible clinics according to preset criteria of ethical relevance. Results: A majority (79%) of UK clinics were judged to be problematic. Information was found to be lacking, misleading or otherwise problematic in several respects, including a lack of information on risks of adverse effects, unjustifiably optimistic depictions of therapeutic effectiveness, and questionable presentational approaches such as the use of celebrity patient testimonials. Conclusion: In a majority of cases, commercial clinics in the UK portray stem cell therapies on their websites in ethically questionable ways.

Truth in Science and Medicine: The Hope and Hype of Stem Cell Therapies

The article examines the practice of cell therapies, often named as stem cell therapies. For the general public this is recognized as promising treatment for many diseases, offering hope for many people to restore health to themselves or their loved ones. However, despite the enormous potential that this type of treatment holds, it has its limitations. The tension between hope, science, truth and deception can come to the fore especially when someone is fighting for their life. Moral and ethical issues play a key role in such cases, serving as guideposts obscured, however, by information noise.