Stem Cell Field Research Articles

Advances in therapies using mesenchymal stem cells and their exosomes for treatment of peripheral nerve injury: state of the art and future perspectives.

"Peripheral nerve injury" refers to damage or trauma affecting nerves outside the brain and spinal cord. Peripheral nerve injury results in movements or sensation impairments, and represents a serious public health problem. Although severed peripheral nerves have been effectively joined and various therapies have been offered, recovery of sensory or motor functions remains limited, and efficacious therapies for complete repair of a nerve injury remain elusive. The emerging field of mesenchymal stem cells and their exosome-based therapies hold promise for enhancing nerve regeneration and function. Mesenchymal stem cells, as large living cells responsive to the environment, secrete various factors and exosomes. The latter are nano-sized extracellular vesicles containing bioactive molecules such as proteins, microRNA, and messenger RNA derived from parent mesenchymal stem cells. Exosomes have pivotal roles in cell-to-cell communication and nervous tissue function, offering solutions to changes associated with cell-based therapies. Despite ongoing investigations, mesenchymal stem cells and mesenchymal stem cell-derived exosome-based therapies are in the exploratory stage. A comprehensive review of the latest preclinical experiments and clinical trials is essential for deep understanding of therapeutic strategies and for facilitating clinical translation. This review initially explores current investigations of mesenchymal stem cells and mesenchymal stem cell-derived exosomes in peripheral nerve injury, exploring the underlying mechanisms. Subsequently, it provides an overview of the current status of mesenchymal stem cell and exosome-based therapies in clinical trials, followed by a comparative analysis of therapies utilizing mesenchymal stem cells and exosomes. Finally, the review addresses the limitations and challenges associated with use of mesenchymal stem cell-derived exosomes, offering potential solutions and guiding future directions.

Cell therapy for neurological disorders.

Cell therapies for neurological disorders are entering the clinic and present unique challenges and opportunities compared with conventional medicines. They have the potential to replace damaged nervous tissue and integrate into the brain or spinal cord to produce functional effects for the lifetime of the patient, which could revolutionize the way clinicians treat debilitating neurological disorders. The major challenge has been cell sourcing, which historically relied mainly on fetal brain tissue. This has largely been overcome with the advent of pluripotent stem cell technology and the ability to make almost any cell of the nervous system at scale. Furthermore, advances in gene editing now allow the generation of genetically modified cells that could perform better and evade the immune system. With all the remarkable new approaches to treat neurological disorders, we take a critical look at the state of current clinical trials and how challenges may be overcome with the evolving technology and innovation occurring in the stem cell field.

Label-free live characterization of mesenchymal stem cell spheroids by biophysical properties measurement

Three-dimensional (3D) cell culture has become a consolidated method in the stem cell field, where mesenchymal stromal stem cells (MSCs) can be used to generate in vitro spheroid aggregates called MSC-Spheroids (MSph). MSph is a floating cluster of stem cells similar to those in literature are known as bone marrow-derived “mesenspheres”. Even though MSC properties are shared by MSph, depending on the cell type and their tissue source, the morphology and degree of compaction of the MSph can be variable, creating limitations in such a cell model. Thus, during culture, a variation in stem cell functionality and viability, in addition to the suitability for comparing MSph in some experimental protocols, can be affected by spheroid biophysical intrinsic properties like mass density. To investigate this limitation and provide a new method for researchers, MSph of seven different tissue sources were compared by combining mass density, weight, and size evaluations with viability assays for ATP measurement. MSph cultured in traditional static conditions showed decreased in viability over the days of culture, while mass density exhibited different trends among cell types. Additionally, treatment of MSph with a non-toxic concentration of a natural compound cell regulator, such as plumbagin, altered the mass density of a selected cell type, thereby confirming the efficacy of the biophysical approach in monitoring MSph variability post-treatment. The results encourage using MSph in the early days of culture after their formation to ensure viability and likely retention of the stem cell phenotype.

When boundaries benefit science and society

In the rapidly moving field of stem cell and embryo research, research questions often sit at the intersection of scientific inquiry and ethical considerations. The International Society for Stem Cell Research (ISSCR) produces guidelines to help navigate decisions in this area. For Cell's 50th Anniversary Focus on Developmental Biology, scientific editor Sarah Geisler discussed the importance of the ISSCR guidelines on stem cell and embryo research for both the stem cell community and the broader public with Amander Clark, Robin Lovell-Badge, and Janet Rossant, who have been involved in the ongoing evolution of the guidelines. A lightly edited transcript of their conversation is shared here.

The 32nd Ion Channels Meeting, 17th-20th September 2023, Sète, France.

The 32nd Ion Channel Meetings were organized by the Ion Channels Association from September 17 to 20, 2023 in the Occitanie region (Sète). Researchers, post-docs and students from France, Europe and non-European countries came together to present and discuss their work on various themes covering the field of neuroscience, stem cells, hypoxia and pathophysiology cardiac. Through the plenary conference given by Professor Emilio Carbone and the 5 conferences organized by the scientific committee, attention was paid this year to autism, neuromotor and cardiac disorders and tumor aggressive processes. The scientific exchanges were enriched by two general conferences on the biometric analysis of publications related to ion channels and a retrospective presentation of proven cases of scientific fraud. These presentations are summarized in this meeting report.

Abstract 118: Development of a novel murine model, NCG-M/hIL15, for enhanced post-HSC transplantation immunoreconstruction

Abstract Advances in the field of immunology and hematopoietic stem cell (HSC) transplantation have prompted the development of murine models that faithfully recapitulate human immune responses. We present the NCG-M/hIL15 model, an innovative advancement in the realm of preclinical research, addressing two key challenges associated with existing models: the limited capacity for human natural killer (NK) cell regeneration in NCG-M and the suboptimal reconstitution of T cells, myeloid lineage cells in NCG-hIL15 mice. Compared to the conventional NCG-M model, the NCG-M/hIL15 model demonstrates a significant improvement in its ability to regenerate human NK cells post-HSC transplantation. This advancement offers a valuable tool for studying NK cell biology, immune surveillance, and antitumor responses. Furthermore, when compared to the NCG-hIL15 model, the NCG-M/hIL15 model outperforms in the reconstitution of human T cells and myeloid lineage cells, contributing to a more comprehensive simulation of human immune responses. The overall survival of mice in this model is notably stable, further enhancing its utility for long-term immunological studies. The NCG-M/hIL15 model not only advances our understanding of human immune responses but also has significant implications for the development of novel immunotherapies and the preclinical evaluation of HSC transplantation strategies. This novel murine model offers a more accurate representation of the human immune system, with the potential to expedite the development of innovative therapeutic interventions. We present this model as a valuable addition to the preclinical research toolkit, promising a deeper understanding of immunology and a brighter future for clinical applications. Citation Format: Huiyi Wang, Jun Xing, Jialu Fan, Yuan Fan, Jing Zhao, Xiang Gao, Cunxiang Ju. Development of a novel murine model, NCG-M/hIL15, for enhanced post-HSC transplantation immunoreconstruction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 118.

Updates and Challenges in ENS Cell Therapy for the Treatment of Neurointestinal Diseases.

Neurointestinal diseases represent a significant challenge in clinical management with current palliative approaches failing to overcome disease and treatment-related morbidity. The recent progress with cell therapy to restore missing or defective components of the gut neuromusculature offers new hope for potential cures. This review discusses the progress that has been made in the sourcing of putative stem cells and the studies into their biology and therapeutic potential. We also explore some of the practical challenges that must be overcome before cell-based therapies can be applied in the clinical setting. Although a number of obstacles remain, the rapid advances made in the enteric neural stem cell field suggest that such therapies are on the near horizon.

Knowledge mapping and research trends of stem cell in wound healing: A bibliometric analysis

AbstractWound nonhealing is a common and difficult problem in clinic. Stem cells are pluripotent cells, and their undifferentiated and self‐replicating characteristics have attracted much attention in the regenerative medicine‐related researches. New treatment approaches might result from an understanding of the function of stem cells in wound healing. Using bibliometric techniques, this study proposed to analyse the research status, hotspots, and research trends in stem cell and wound healing. By using the Web of Science Core Collection (WoSCC), we conducted an in‐depth review of publications on stem cells in wound healing from 1999 to 2023. We used scientometric analysis methods to examine annual trends, institutions, countries, journals, authors, keywords, co‐occurrence references and their closed relationship, revealing present hotspots and potential future advancements in this field. We analysed 19 728 English studies and discovered a consistent rise in annual publications. The United States and China were the two countries with the most publications. The most three influential institutions in the field were Shanghai Jiao Tong University, Sun Yat‐sen University, and University of Pittsburgh. International Journal of Molecular Sciences and Biomaterials were considered the most influential journals in this field. International Journal of Molecular Sciences had the most publications, and the most quantity of citations and the highest H‐index were found in Biomaterials. The dual‐map overlay revealed that publications in Molecular/Biology/Genetics and Health/Nursing/Medicine co‐cited journals received the majority of the citations for studies from Molecular/Biology/Immunology and Medicine/Medical/Clinical. In terms of publication production and influence, Fu X stood out among the authors, and Pittenger MF took the top spot in co‐citations. According to the keywords from the analysis, future research should concentrate on the mechanisms through which stem cells promote wound healing. We conducted a thorough analysis of the general information, knowledge base and research hotspots in the field of stem cells and wound healing from 1999 to 2023 by using the VOSviewer, CiteSpace, and other bibliometric analysis tools. It not only provided valuable insights for scholars, but also served as a reliable reference that drives further development in the field and stimulates the interest of researchers.

Application progress of single-cell sequencing technology in mesenchymal stem cells research.

Single-Cell Sequencing (SCS) technology plays an important role in the field of Mesenchymal Stem Cells (MSCs) research. This paper comprehensively describes the application of SCS technology in the field of MSCs research, including (1) SCS enables more precise MSCs characterization and biomarker definition. (2) SCS reveals the prevalent gene expression heterogeneity among different subclusters within MSCs, which contributes to a more comprehensive understanding of MSCs function and diversity in developmental, regenerative, and pathological contexts. (3) SCS provides insights into the dynamic transcriptional changes experienced by MSCs during differentiation and the complex web of important signaling pathways and regulatory factors controlling key processes within MSCs, including proliferation, differentiation and regulation, and interactions mechanisms. (4) The analytical methods underpinning SCS data are rapidly evolving and converging with the field of histological research to systematically deconstruct the functions and mechanisms of MSCs. This review provides new perspectives for unraveling the biological properties, heterogeneity, differentiation potential, biological functions, and clinical potential of MSCs at the single-cell level.

Bibliometric Analysis of Stem Cells in Ischemic Stroke (2001-2022): Trends, Hotspots and Prospects.

Background: Ischemic stroke is a common cerebrovascular accident with a high risk of neurological deficits. Stem cell therapy has progressively attracted the interest of scientists and clinicians due to the benefits of promoting neural regeneration and regulating the microenvironment surrounding the lesion after ischemic stroke. Our study aimed to evaluate the development trends and research hotspots in the field of stem cells and ischemic stroke. Materials and methods: Publications related to stem cells and ischemic stroke were retrieved from the Web of Science from 2001 to 2022. Data analysis and mapping were performed using VOSviewer, Citespace and ImageGP. Results: In total, 1932 papers were included in the analysis. Publications have steadily increased over the past 22 years. China has contributed the maximum number of publications, whereas the USA ranked first in the total number of citations and was considered the center of the international collaboration network. University of South Florida, Henry Ford Hospital, and Oakland University were the most influential institutions. Stroke, Brain Research, and Neural Regeneration Research were the most productive journals. The research in this field was primarily focused on the effects of stem cells on neurogenesis, inflammation, and angiogenesis following ischemic stroke, as well as their therapeutic potential for the disease. In addition, neural stem cells and mesenchymal stem cells are the most commonly utilized stem cells. The topics related to miRNA, extracellular vesicles, exosomes, mesenchymal stem cells, neuroinflammation, and autophagy are current research hotspots. Conclusion: Our bibliometric study provides a novel perspective on the research trends in the field of stem cells and ischemic stroke. The outcome of this study may benefit scientists to identify research hotspots and development directions, thereby advancing the application of stem cell-based therapy for ischemic stroke.

Divergent Roles of KLF4 During Primordial Germ Cell Fate Induction from Human Embryonic Stem Cells.

As a core transcriptional factor regulating pluripotency, Krüppel-like factor 4 (KLF4) has gained much attention in the field of stem cells during the past decades. However, few research have focused on the function of KLF4 during human primordial germ cell (PGC) specification. Here, we induced human PGC-like cells (hPGCLCs) from human embryonic stem cells (hESCs) and the derived hPGCLCs upregulated PGC-related genes, like SOX17, BLIMP1, TFAP2C, NANOS3, and the naïve pluripotency gene KLF4. The KLF4-knockout hESCs formed typical multicellular colonies with clear borders, expressed pluripotency genes, such as NANOG, OCT4, and SOX2, and exhibited no differences in proliferation capacity compared with wild type hESCs. Notably, KLF4 deletion in hESCs did not influence the induction of PGCLCs in vitro. In contrast, overexpression of KLF4 during PGC induction process inhibited the efficiency of PGCLC formation from hESCs in vitro. Overexpression of KLF4 may regenerate the naïve ground state in hESCs and results in repression for PGC specification. Thus, KLF4 could be a downstream target of human PGC program and the upregulation of KLF4 is prepared for late stage of germline development.

Organoid Culture Applications: Mini Systematic Review

Recent scientific developments in the stem cell field have made it possible to create complex organoids, or structures that resemble complete organs, in vitro. In the majority of these methods, stem cells produced from stem cells or tissue progenitors are allowed to self-organize into three-dimensional (3D) structures using culture systems in three dimensions. The purpose of this study is to ascertain the use of organoid culture in the area of health. This kind of study employs the literature review methodology. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) criteria are referenced throughout the stages of the literature review performed in this study. The four processes that make up this level are identification, screening, eligibility, and acceptance. These discoveries showing that human stem cells and patient-derived pluripotent stem cells can be used to generate organoids open up a wide range of opportunities for modeling and disease development, toxicological research and medication discovery, and the field of regenerative medicine. Here, we discuss some of the most significant recent advancements in 3D human organoid production as well as the field's historical advancements. Finally, we discuss present restrictions and provide illustrations of how organoid technology may be used in the healthcare industry.

The variability of judicial decisions in the stem cell industry in China.

As China's stem cell industry continues to develop, increasing disputes concerning stem cell-based interventions have been brought before the courts. Nonetheless, there is variability in the courts' understanding and attitude toward the regulatory attributes of these interventions, which to some extent has multifaceted impacts on the stem cell field.

Investigation Into the Potential Prospects of Induced Pluripotent Stem Cells

Cell cultures and stem cell studies have revolutionized the field of biotechnology and regenerative medicine by opening various medicine sectors that were once closed due to lack of information and technology. The potent ability of stem cells has proven to be really significant in the field of medical research for treating degenerative diseases and disorders, thus developing novel therapeutics. Induced pluripotent stem cells are created by reprogramming adult cells to behave like an embryonic-like pluripotent state cell. The reprogramming of cells is done by introducing specific combinations or sets of genes into the cells using viral vectors. This in turn resets the genetic program and reprograms the cells in a way that the cells can differentiate into any type of cell in the human body. Induced pluripotent stem cells have the ability to self-renew and differentiate into all cell types, also including gametes. This type of stem cell can be cultured in lab, and have been proven to renew themselves indefinitely. These cells can be reprogrammed from cells obtained from any healthy person or patient. Stem cells are considered as a valuable resource in the field of medicine but pluripotent stem cells in nature are embryonic stem cells, so their study and isolation posed multiple ethical barriers to be overcome, and inducing pluripotent nature in adult cells has proven to be a solution to overcome those barriers. Induced pluripotent stem cells are considered to be the key for regenerative medicine as their potent ability can be manipulated to replace any diseased or damaged tissues. The authors have discussed the current status of induced pluripotent stem cells and their potential future prospects in this paper. There are also a lot of ethical and legal challenges and opportunities that must be overcome to fully exploit the potential of stem cells. Overall, the aim of this paper is to shed light on the significance of the study and development of stem cells and its research in the field of medicine, and its potential to formulate newer therapies and therapeutics. The authors tend to provide an overview of stem cell research and hope to inspire further research and development in this area to generate significant results in novel and effective stem-cell based therapies.

Regulation of adult stem cell function by ketone bodies.

Adult stem cells play key roles in tissue homeostasis and regeneration. Recent evidence suggests that dietary interventions can significantly impact adult stem cell function. Some of these effects depend on ketone bodies. Adult stem cells could therefore potentially be manipulated through dietary regimens or exogenous ketone body supplementation, a possibility with significant implications for regenerative medicine. In this review we discuss recent findings of the mechanisms by which ketone bodies could influence adult stem cells, including ketogenesis in adult stem cells, uptake and transport of circulating ketone bodies, receptor-mediated signaling, and changes to cellular metabolism. We also discuss the potential effects of ketone bodies on intracellular processes such as protein acetylation and post-transcriptional control of gene expression. The exploration of mechanisms underlying the effects of ketone bodies on stem cell function reveals potential therapeutic targets for tissue regeneration and age-related diseases and suggests future research directions in the field of ketone bodies and stem cells.

An Efficient Protocol for CUT&RUN Analysis of FACS-Isolated Mouse Satellite Cells.

Genome-wide analyses with small cell populations are a major constraint for studies, particularly in the stem cell field. This work describes an efficient protocol for the fluorescence-activated cell sorting (FACS) isolation of satellite cells from the limb muscle, a tissue with a high content of structural proteins. Dissected limb muscles from adult mice were mechanically disrupted by mincing in medium supplemented with dispase and type I collagenase. Upon digestion,the homogenate was filtered through cell strainers, and cells were suspended in FACS buffer. Viability was determined with fixable viability stain, and immunostained satellite cells were isolated by FACS. Cells were lysed with Triton X-100 and released nuclei were bound to concanavalin A magnetic beads. Nucleus/bead complexes were incubated with antibodies against the transcription factor or histone modifications of interest. After washes, nucleus/bead complexes were incubated with protein A-micrococcal nuclease, and chromatin cleavage was initiated with CaCl2. After DNA extraction, libraries were generated and sequenced, and the profiles for genome-wide transcription factor binding and covalent histone modifications were obtained by bioinformatic analysis. The peaks obtained for the various histone marks showed that the binding events were specific for satellite cells. Moreover, known motif analysis unveiled that the transcription factor was bound to chromatin via its cognate response element. This protocol is therefore adapted to study gene regulation in adult mice limb muscle satellite cells.

AKAP12 promotes cancer stem cell-like phenotypes and activates STAT3 in colorectal cancer.

Cancer stem cells (CSCs) have unique biological characteristics, including tumorigenicity, immortality, and chemoresistance. Colorectal CSCs have been identified and isolated from colorectal cancers by various methods. AKAP12, a scaffolding protein, is considered to act as a potential suppressor in colorectal cancer, but its role in CSCs remains unknown. In this study, we investigated the function of AKAP12 in Colorectal CSCs. Herein, Colorectal CSCs were enriched by cell culture with a serum-free medium. CSC-associated characteristics were evaluated by Flow cytometry assay and qPCR. AKAP12 gene expression was regulated by lentiviral transfection assay. The tumorigenicity of AKAP12 in vivo by constructing a tumor xenograft model. The related pathways were explored by qPCR and Western blot. The depletion of AKAP12 reduced colony formation, sphere formation, and expression of stem cell markers in colorectal cancer cells, while its knockdown decreased the volume and weight of tumor xenografts in vivo. AKAP12 expression levels also affected the expression of stemness markers associated with STAT3, potentially via regulating the expression of protein kinase C. This study suggests Colorectal CSCs overexpress AKAP12 and maintain stem cell characteristics through the AKAP12/PKC/STAT3 pathway. AKAP12 may be an important therapeutic target for blocking the development of colorectal cancer in the field of cancer stem cells.

‘Good’ and ‘bad’ stem cell research: How India's scientists view providers of unproven stem cell treatments

In this article, I explore the opinions of India's stem cell scientists on unproven and unregulated stem cell treatment provision in the country's private health sector. Drawing on interviews, I describe three themes, namely ethical responsibility; exaggerated timelines for stem cell cures; and the scientific method to demonstrate how scientists make distinctions between themselves as producers of ‘good stem cell research’ and treatment providers who practice ‘bad stem cell research’. Excerpts from my interviews with treatment providers interrupt the discussions in the themes, offering insights on conflicting views of medical professionals. I analyse the themes using the conceptual framework of ‘boundary-work’ that Gieryn developed in order to examine how scientists respond to challenges to their intellectual authority in particular scientific fields. A policy environment that promotes product development posed a threat to the integrity of basic science according to stem cell scientists who simultaneously reflected on solutions to advancing India's stem cell field by promoting the role of clinician-researchers as mediators between medicine and science. According to Gieryn, depending on what is at stake such as funding and public support, scientists redraw boundaries in order to secure their position in relation to competing groups. In this instance, I argue that the expectations of translational research, demanded that scientists examine the boundaries drawn between themselves and clinicians with the purpose of also including the latter in stem cell science rather than for excluding contenders, as Gieryn's notion of boundary-work suggested.

Preclinical Research of Stem Cells: Challenges and Progress.

In recent years, great breakthroughs have been made in basic research and clinical applications of stem cells in regenerative medicine and other fields, which continue to inspire people to explore the field of stem cells. With nearly unlimited self-renewal ability, stem cells can generate at least one type of highly differentiated daughter cell, which provides broad development prospects for the treatment of human organ damage and other diseases. In the field of stem cell research, related technologies for inducing or isolating stem cells are relatively mature, and a variety of stable stem cell lines have been successfully constructed. To realize the full clinical application of stem cells as soon as possible, it is more and more important to further optimize each stage of stem cell research while conforming to Current Good Manufacture Practices (cGMP) standards. Here, we synthesized recent developments in stem cell research and focus on the introduction of xenogenicity in the preclinical research process and the remaining problems of various cell bioreactors. Our goal is to promote the development of technologies for xeno-free culture and clinical expansion of stem cells through in-depth discussion of current research. This review will provide new insight into stem cell research protocols and will contribute to the creation of efficient and stable stem cell expansion systems.

Notch and Wnt Signaling Modulation to Enhance DPSC Stemness and Therapeutic Potential.

The Dental Pulp of permanent human teeth is home to stem cells with remarkable multilineage differentiation ability: human Dental Pulp Stem Cells (DPSCs). These cells display a very notorious expression of pluripotency core factors, and the ability to give rise to mature cell lineages belonging to the three embryonic layers. For these reasons, several researchers in the field have long considered human DPSCs as pluripotent-like cells. Notably, some signaling pathways such as Notch and Wnt contribute to maintaining the stemness of these cells through a complex network involving metabolic and epigenetic regulatory mechanisms. The use of recombinant proteins and selective pharmacological modulators of Notch and Wnt pathways, together with serum-free media and appropriate scaffolds that allow the maintenance of the non-differentiated state of hDPSC cultures could be an interesting approach to optimize the potency of these stem cells, without a need for genetic modification. In this review, we describe and integrate findings that shed light on the mechanisms responsible for stemness maintenance of hDPSCs, and how these are regulated by Notch/Wnt activation, drawing some interesting parallelisms with pluripotent stem cells. We summarize previous work on the stem cell field that includes interactions between epigenetics, metabolic regulations, and pluripotency core factor expression in hDPSCs and other stem cell types.