Stem Cell Regenerative Medicine Research Articles

The Application of Biomaterials in Spinal Cord Injury.

The spinal cord and the brain form the central nervous system (CNS), which is the most important part of the body. However, spinal cord injury (SCI) caused by external forces is one of the most difficult types of neurological injury to treat, resulting in reduced or even absent motor, sensory and autonomic functions. It leads to the reduction or even disappearance of motor, sensory and self-organizing nerve functions. Currently, its incidence is increasing each year worldwide. Therefore, the development of treatments for SCI is urgently needed in the clinic. To date, surgery, drug therapy, stem cell transplantation, regenerative medicine, and rehabilitation therapy have been developed for the treatment of SCI. Among them, regenerative biomaterials that use tissue engineering and bioscaffolds to transport cells or drugs to the injured site are considered the most promising option. In this review, we briefly introduce SCI and its molecular mechanism and summarize the application of biomaterials in the repair and regeneration of tissue in various models of SCI. However, there is still limited evidence about the treatment of SCI with biomaterials in the clinic. Finally, this review will provide inspiration and direction for the future study and application of biomaterials in the treatment of SCI.

Investigating the potential of stem cells in regenerative medicine

Regenerative medicine is a fast-developing field of study that hopes to usher in a new era of healthcare in which severe diseases and injuries may be efficiently treated and reversed. Stem cells have the potential to transform medicine and improve health worldwide. This study explores the diverse field of stem cell research in regenerative medicine, including their origins, sophisticated differentiation techniques, therapeutic applications, and ethical implications. The findings of this study show the tremendous effect of stem cell-based therapy on a wide range of illnesses and injuries. Combining stem cell therapies with gene therapy, immunotherapy, and pharmacology gives hope for improving treatment results and addressing complex disease processes.

Therapeutic Effect of Human Adipocyte-derived Stem Cell-derived Exosomes on a Transgenic Mouse Model of Parkinson's Disease.

Stem cell therapy and regenerative medicine are promising for treating Parkinson's disease (PD) not only for the potential for cell replacement but also for the paracrine effect of stem cell secretion, especially proteins and nucleotide-enriched exosomes. This study investigated the neuroprotective effect of exosomes secreted from human adipocyte-derived stem cells (hADSCs) on PD. hADSCs were isolated from the visceral fat tissue of individuals without PD who underwent bariatric surgery and were validated using surface markers and differentiation ability. Exosomes were isolated from the culture medium of hADSCs through serial ultracentrifugation and validated. Condensed exosomes were administered intravenously to 12-week-old MitoPark mice, transgenic parkinsonism mouse model with conditional knockout of mitochondrial transcription factor A in dopaminergic neurons, monthly for 3 months. Motor function, gait, and memory were assessed monthly, and immunohistochemical analysis of neuronal and inflammatory markers was performed at the end of the experiments. The hADSC-derived exosome-treated mice exhibited better motor function in beam walking and gait analyses than did the untreated mice. In the novel object recognition tests, the exosome-treated mice retained better memory function. Immunohistochemical analysis revealed that although exosome treatment did not prevent the loss of dopaminergic neurons in the substantia nigra of mice, it down-regulated microglial activation and neuroinflammation in the midbrain. hADSC-derived exosomes were neuroprotective in this in vivo mouse model of PD, likely because of their anti-inflammatory effect. Use of hADSC-derived exosomes may offer several beneficial effects in stem cell therapy. Since they can also be produced at an industrial level, they are a promising treatment option for PD and other neurodegenerative diseases.

The centrality of proteoglycan research: Expect the unexpected

The centrality of proteoglycan research: Expect the unexpected

Industry updates from the field of stem cell research and regenerative medicine in October 2022.

Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from non-academic institutions in October 2022.

A novel agonist with homobivalent single-domain antibodies that bind the FGF receptor 1 domain III functions as an FGF2 ligand

Fibroblast growth factor (FGF) is a multifunctional protein that exhibits a wide range of biological effects. Most commonly, it acts as a mitogen, but it also has regulatory, morphological, and endocrine effects. The four receptor subtypes of FGF are activated by more than 20 different FGF ligands. FGF2, one of the FGF ligands, is an essential factor for cell culture in stem cells for regenerative medicine; however, recombinant FGF2 is extremely unstable. Here, we successfully generated homobivalent agonistic single-domain antibodies (variable domain of heavy chain of heavy chain antibodies referred to as VHHs) that bind to domain III and induce activation of the FGF receptor 1 and thus transduce intracellular signaling. This agonistic VHH has similar biological activity (EC50) as the natural FGF2 ligand. Furthermore, we determined that the agonistic VHH could support the proliferation of human-induced pluripotent stem cells (PSCs) and human mesenchymal stem cells, which are PSCs for regenerative medicine. In addition, the agonistic VHH could maintain the ability of mesenchymal stem cells to differentiate into adipocytes or osteocytes, indicating that it could maintain the properties of PSCs. These results suggest that the VHH agonist may function as an FGF2 mimetic in cell preparation of stem cells for regenerative medicine with better cost effectiveness.

LncRNA Osilr9 coordinates promoter DNA demethylation and the intrachromosomal loop structure required for maintaining stem cell pluripotency

Nuclear reprogramming of somatic cells into a pluripotent status has the potential to create patient-specific induced pluripotent stem cells for regenerative medicine. Currently, however, the epigenetic mechanisms underlying this pluripotent reprogramming are poorly understood. To delineate this epigenetic regulatory network, we utilized a chromatin RNA in situ reverse transcription sequencing (CRIST-seq) approach to identify long noncoding RNAs (lncRNAs) embedded in the 3-dimensional intrachromosomal architecture of stem cell core factor genes. By combining CRIST-seq and RNA sequencing, we identified Oct4-Sox2 interacting lncRNA 9 (Osilr9) as a pluripotency-associated lncRNA. Osilr9 expression was associated with the status of stem cell pluripotency in reprogramming. Using short hairpin RNA (shRNA) knockdown, we showed that this lncRNA was required for the optimal maintenance of stem cell pluripotency. Overexpression of Osilr9 induced robust activation of endogenous stem cell core factor genes in fibroblasts. Osilr9 participated in the formation of the intrachromosomal looping required for the maintenance of pluripotency. After binding to the Oct4 promoter, Osilr9 recruited the DNA demethylase ten-eleven translocation 1, leading to promoter demethylation. These data demonstrate that Osilr9 is a critical chromatin epigenetic modulator that coordinates the promoter activity of core stem cell factor genes, highlighting the critical role of pluripotency-associated lncRNAs in stem cell pluripotency and reprogramming.

Mesenchymal stem cells for regenerative medicine in central nervous system.

Mesenchymal stem cells (MSCs) are multipotent stem cells, whose paracrine and immunomodulatory potential has made them a promising candidate for central nervous system (CNS) regeneration. Numerous studies have demonstrated that MSCs can promote immunomodulation, anti-apoptosis, and axon re-extension, which restore functional neural circuits. The therapeutic effects of MSCs have consequently been evaluated for application in various CNS diseases including spinal cord injury, cerebral ischemia, and neurodegenerative disease. In this review, we will focus on the research works published in the field of mechanisms and therapeutic effects of MSCs in CNS regeneration.

Reprogramming stem cells in regenerative medicine

AbstractInduced pluripotent stem cells (iPSCs) that are generated from adult somatic cells are induced to express genes that make them pluripotent through reprogramming techniques. With their unlimited proliferative capacity and multifaceted differentiation potential and circumventing the ethical problems encountered in the application of embryonic stem cells (ESC), iPSCs have a broad application in the fields of cell therapy, drug screening, and disease models and may open up new possibilities for regenerative medicine to treat diseases in the future. In this review, we begin with different reprogramming cell technologies to obtain iPSCs, including biotechnological, chemical, and physical modulation techniques, and present their respective strengths, and limitations, as well as the recent progress of research. Secondly, we review recent research advances in iPSC reprogramming‐based regenerative therapies. iPSCs are now widely used to study various clinical diseases of hair follicle defects, myocardial infarction, neurological disorders, liver diseases, and spinal cord injuries. This review focuses on the translational clinical research around iPSCs as well as their potential for growth in the medical field. Finally, we summarize the overall review and look at the potential future of iPSCs in the field of cell therapy as well as tissue regeneration engineering and possible problems. We believe that the advancing iPSC research will help drive long‐awaited breakthroughs in cellular therapy.

Application of stem cells combined with biomaterial in the treatment of intervertebral disc degeneration.

As the world population is aging, intervertebral disc degeneration (IDD) is becoming a global health issue of increasing concern. A variety of disc degeneration diseases (DDDs) have been proven to be associated with IDD, and these illnesses have significant adverse effects on both individuals and society. The application of stem cells in regenerative medicine, such as blood and circulation, has been demonstrated by numerous studies. Similarly, stem cells have made exciting progress in the treatment of IDD. However, due to complex anatomical structures and functional requirements, traditional stem cell injection makes it difficult to meet people's expectations. With the continuous development of tissue engineering and biomaterials, stem cell combined with biomaterials has far more prospects than before. This review aims to objectively and comprehensively summarize the development of stem cells combined with contemporary biomaterials and the difficulties that need to be overcome.

A review of regenerative therapy for spinal cord injury using human iPS cells

Spinal cord injury (SCI) has been considered to cause sudden, irreversible loss of function in patients. However, developments in stem cell biology and regenerative medicine are changing this conventional notion. Here we reviewed the overview of regenerative medicine of SCI.As a consequence of the establishment of human induced pluripotent stem cells (hiPSCs), hiPSC-based therapies for SCI, such as neural stem/progenitor cell (NS/PC) transplantation, have emerged as promising therapeutic modalities. Using several animal models, hiPSC-NS/PC transplantation into subacute injured spinal cords has been repeatedly demonstrated to improve locomotor function.Some biological mechanisms underlying this improvement have been proposed. In particular, combined with advanced neuroscience techniques such as designer receptors exclusively activated by designer drugs (DREADDs), neuronal relay theory, in which the transplanted cell-derived neurons reconstruct disrupted neuronal circuits, was proven to be involved histologically, pharmaceutically, electrophysiologically, and via in vivo bioimaging.Based on these findings, hiPSC-NS/PC transplantation for subacute SCI was moved ahead to a clinical study on human patients. At the same time, the search for effective treatments for chronic SCI is proceeding gradually, combining hiPSC-NS/PC transplantation with other treatment modalities such as rehabilitation, pharmaceutical interventions, or optimal scaffolds. In addition to NS/PCs, oligodendrocyte precursor cells (OPCs) are also a promising cell source for transplantation, as demyelinated axons affected by SCI can be repaired by OPCs. Therapies with OPCs derived from hiPSCs are still in preclinical studies but have shown favorable outcomes in animal models.In the future, several therapeutic options may be available according to the pathological conditions and the time period of SCI. Moreover, the application of regenerative therapy for the spinal cord could be broadened to degenerative disorders, such as spinal canal stenosis.Summary sentence: A historical review of human induced pluripotent stem cell (hiPSC) based cell transplantation therapy for spinal cord injury (SCI), in particular about footsteps of hiPSC-derived neural stem/progenitor cell transplantation, recent clinical study, and its future perspective.

Industry updates from the field of stem cell research and regenerative medicine in September 2022.

Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from non-academic institutions in September 2022.

A scoping review of regenerative medicine in medical education

Stem cell therapeutics and regenerative medicine have taken a strong foothold in biomedicine. However, most physicians are currently not adequately prepared to identify, refer, and deliver safe regenerative therapies. To understand this gap, we sought to characterize published literature on current physician training in regenerative medicine. Our scoping review describes current training strategies to bridge the gap and integrate such education into medical curricula for adequate training.

First person – Vinay Kumar Dubey

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Vinay Kumar Dubey is first author on ‘ S. mediterranea ETS-1 regulates the function of cathepsin-positive cells and the epidermal lineage landscape via basement membrane remodeling’, published in JCS. Vinay Kumar is a PhD student in the lab of Dr Dasaradhi Palakodeti at the Institute for Stem Cell Sciences and Regenerative Medicine (inStem), Bangalore, India, investigating extracellular factors that govern maintenance and differentiation of adult pluripotent stem cell in planaria.

Industry Updates From the Field of Stem Cell Research and Regenerative Medicine in August 2022

Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from non-academic institutions in August 2022.

Cross-lineage potential of Ascl1 uncovered by comparing diverse reprogramming regulatomes.

Direct reprogramming has revolutionized the fields of stem cell biology and regenerative medicine. However, the common mechanisms governing how reprogramming cells undergo transcriptome and epigenome remodeling (i.e., regulatome remodeling) have not been investigated. Here, by characterizing early changes in the regulatome of three different types of direct reprogramming, we identify lineage-specific features as well as common regulatory transcription factors. Of particular interest, we discover that the neuronal factor Ascl1 possesses cross-lineage potential; together with Mef2c, it drives efficient cardiac reprogramming toward a mature and induced cardiomyocyte phenotype. Through ChIP-seq and RNA-seq, we find that MEF2C drives the shift in ASCL1 binding away from neuronal genes toward cardiac genes, guiding their co-operative epigenetic and transcription activities. Together, these findings demonstrate the existence of common regulators of different direct reprogramming and argue against the premise that transcription factors possess only lineage-specific capabilities for altering cell fate - the basic premise used to develop direct reprogramming approaches.

Photobiomodulation improves the therapeutic efficacy of mesenchymal stem cells in regenerative medicine

Other SectionsAbstractINTRODUCTIONPBM AND DIFFERENT SOURCES OF MSCSPBM MECHANISMS OF ACTIONSCARCITY IN STANDARDIZATION OF PARAMETERS IN PBM PROCEDURESCONCLUSIONCONFLICT OF INTERESTAUTHOR CONTRIBUTIONSFUNDINGReferences

3D in-vitro cultures of human bone marrow and Wharton's jelly derived mesenchymal stromal cells show high chondrogenic potential.

In this study, chondrogenic potentials of 3D high-density cultures of Bone Marrow (BM) and Wharton’s Jelly (WJ)-derived mesenchymal stromal cells (MSCs) was investigated by chondrogenesis- and cytokine-related gene expression over a 16-day culture period supplemented with human transforming growth factor (hTGF)-β1 at 10 ng/ml. In BM-MSC 3D models, a marked upregulation of chondrogenesis-related genes, such as SOX9, COL2A1, and ACAN (all p < 0.05) and formation of spherical pellets with structured type II collagen fibers were observed. Similarly, WJ-based high-density culture appeared higher in size and more regular in shape, with a significant overexpression of COL2A1 and ACAN (all p < 0.05) at day 16. Moreover, a similar upregulation trend was documented for IL-6 and IL-10 expression in both BM and WJ 3D systems. In conclusion, MSC-based high-density cultures can be considered a promising in vitro model of cartilage regeneration and tissue engineering. Moreover, our data support the use of WJ-MSCs as a valid alternative for chondrogenic commitment of stem cells in regenerative medicine.

Mesenchyme Stem Cell-Derived Conditioned Medium as a Potential Therapeutic Tool in Idiopathic Pulmonary Fibrosis.

Mesenchyme Stem Cells (MSCs) are the most used types of stem cells in regenerative medicine. Regenerative medicine is a rapidly emerging medicine section that creates new methods to regrow, restore, and replace diseased and damaged tissues, organs, and cells. Scholars have shown a positive correlation between MSCs-based therapies and successful treatment of diseases like cardiac ischemia, cartilage problems, bone diseases, diabetes, and even neurological disorders. Although MSCs have several varying features that make them unique, their immuno-regulatory effects in tissue repair emerge from their secretion of paracrine growth factors, exosomes, and cytokines. These cells secrete a secretome, which has regenerative and reparative properties that lead to injury amelioration, immune modulation, or fibrosis reduction. Recent studies have shown that the administration MCSs derived conditioned medium (MSCs-CM) in acute doses in humans is safe and well-tolerated. Studies from animal models and human clinical trials have also shown that they are efficacious tools in regenerative medicine. In this review, we will explore the therapeutic potential of MSCs-CM in pulmonary fibrosis, with further insight into the treatment of Idiopathic Pulmonary Fibrosis (IPF).

Nano-material utilization in stem cells for regenerative medicine.

The utilization of nanotechnology in regenerative medicine has been globally proven to be the main solution to many issues faced with tissue engineering today, andthe theoretical and empirical investigations of the association of nanomaterials with stem cells have made significant progress as well. For their ability to self-renew and differentiate into a variety of cell types, stem cells have become popular candidates for cell treatment inrecent years, particularly in cartilage and Ocular regeneration. However, there are still several challenges to overcome before it may be used in a wide range of therapeutic contexts. This review paper provides a review of the various implications of nanomaterials in tissue andcell regeneration, the stem cell and scaffold application in novel treatments, and the basic developments in stem cell-based therapies, as well as the hurdles thatmust be solved for nanotechnology to be used in itsfull potential. Due to the increased interest in thecontinuously developing field of nanotechnology, demonstrating, and pinpointing the most recognized and used applications of nanotechnology in regenerative medicine became imperative to provide students, researchers, etc. who are interested.