Field Of Regenerative Medicine Research Articles

BMP7-Loaded Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Ameliorate Liver Fibrosis by Targeting Activated Hepatic Stellate Cells.

Human umbilical cord mesenchymal stem cell (hucMSC)-derived small extracellular vesicles (sEVs) are natural nanocarriers with promising potential in treating liver fibrosis and have widespread applications in the fields of nanomedicine and regenerative medicine. However, the therapeutic efficacy of natural hucMSC-sEVs is currently limited owing to their non-specific distribution in vivo and partial removal by mononuclear macrophages following systemic delivery. Thus, the therapeutic efficacy can be improved through the development of engineered hucMSC-sEVs capable to overcome these limitations. To improve the anti-liver fibrosis efficacy of hucMSC-sEVs, we genetically engineered hucMSC-sEVs to overexpress the anti-fibrotic gene bone morphogenic protein 7 (BMP7) in parental cells. This was achieved using lentiviral transfection, following which BMP7-loaded hucMSC-sEVs were isolated through ultracentrifugation. First, the liver fibrosis was induced in C57BL/6J mice by intraperitoneal injection of 50% carbon tetrachloride (CCL4) twice a week for 8 weeks. These mice were subsequently treated with BMP7+sEVs via tail vein injection, and the anti-liver fibrosis effect of BMP7+sEVs was validated using small animal in vivo imaging, immunohistochemistry (IHC), tissue immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). Finally, cell function studies were performed to confirm the in vivo results. Liver imaging and liver histopathology confirmed that the engineered hucMSC-sEVs could reach the liver of mice and aggregate around activated hepatic stellate cells (aHSCs) with a significantly stronger anti-liver fibrosis effect of BMP7-loaded hucMSC-sEVs compared to those of blank or negative control-transfected hucMSC-sEVs. In vitro, BMP7-loaded hucMSC-sEVs promoted the phenotypic reversal of aHSCs and inhibited their proliferation to enhance the anti-fibrotic effects. These engineered BMP7-loaded hucMSC-sEVs offer a novel and promising strategy for the clinical treatment of liver fibrosis.

Evolving Therapeutic Landscape of Intracerebral Hemorrhage: Emerging Cutting-Edge Advancements in Surgical Robots, Regenerative Medicine, and Neurorehabilitation Techniques.

Intracerebral hemorrhage (ICH) is the most serious form of stroke and has limited available therapeutic options. As knowledge on ICH rapidly develops, cutting-edge techniques in the fields of surgical robots, regenerative medicine, and neurorehabilitation may revolutionize ICH treatment. However, these new advances still must be translated into clinical practice. In this review, we examined several emerging therapeutic strategies and their major challenges in managing ICH, with a particular focus on innovative therapies involving robot-assisted minimally invasive surgery, stem cell transplantation, in situ neuronal reprogramming, and brain-computer interfaces. Despite the limited expansion of the drug armamentarium for ICH over the past few decades, the judicious selection of more efficacious therapeutic modalities and the exploration of multimodal combination therapies represent opportunities to improve patient prognoses after ICH.

Dynamic Roles of Signaling Pathways in Maintaining Pluripotency of Mouse and Human Embryonic Stem Cells.

Culturing of mouse and human embryonic stem cells (ESCs) in vitro was a major breakthrough in the field of stem cell biology. These models gained popularity very soon mainly due to their pluripotency. Evidently, the ESCs of mouse and human origin share typical phenotypic responses due to their pluripotent nature, such as self-renewal capacity and potency. The conserved network of core transcription factors regulates these responses. However, significantly different signaling pathways and upstream transcriptional networks regulate expression and activity of these core pluripotency factors in ESCs of both the species. In fact, ample evidence shows that a pathway, which maintains pluripotency in mouse ESCs, promotes differentiation in human ESCs. In this review, we discuss the role of canonical signaling pathways implicated in regulation of pluripotency and differentiation particularly in mouse and human ESCs. We believe that understanding these distinct and at times-opposite mechanisms-is critical for the progress in the field of stem cell biology and regenerative medicine.

Challenges and Considerations of Preclinical Development for iPSC-Based Myogenic Cell Therapy.

Cell therapies derived from induced pluripotent stem cells (iPSCs) offer a promising avenue in the field of regenerative medicine due to iPSCs' expandability, immune compatibility, and pluripotent potential. An increasing number of preclinical and clinical trials have been carried out, exploring the application of iPSC-based therapies for challenging diseases, such as muscular dystrophies. The unique syncytial nature of skeletal muscle allows stem/progenitor cells to integrate, forming new myonuclei and restoring the expression of genes affected by myopathies. This characteristic makes genome-editing techniques especially attractive in these therapies. With genetic modification and iPSC lineage specification methodologies, immune-compatible healthy iPSC-derived muscle cells can be manufactured to reverse the progression of muscle diseases or facilitate tissue regeneration. Despite this exciting advancement, much of the development of iPSC-based therapies for muscle diseases and tissue regeneration is limited to academic settings, with no successful clinical translation reported. The unknown differentiation process in vivo, potential tumorigenicity, and epigenetic abnormality of transplanted cells are preventing their clinical application. In this review, we give an overview on preclinical development of iPSC-derived myogenic cell transplantation therapies including processes related to iPSC-derived myogenic cells such as differentiation, scaling-up, delivery, and cGMP compliance. And we discuss the potential challenges of each step of clinical translation. Additionally, preclinical model systems for testing myogenic cells intended for clinical applications are described.

Advancing diabetes treatment: the role of mesenchymal stem cells in islet transplantation.

Diabetes mellitus, a prevalent global health challenge, significantly impacts societal and economic well-being. Islet transplantation is increasingly recognized as a viable treatment for type 1 diabetes that aims to restore endogenous insulin production and mitigate complications associated with exogenous insulin dependence. We review the role of mesenchymal stem cells (MSCs) in enhancing the efficacy of islet transplantation. MSCs, characterized by their immunomodulatory properties and differentiation potential, are increasingly seen as valuable in enhancing islet graft survival, reducing immune-mediated rejection, and supporting angiogenesis and tissue repair. The utilization of MSC-derived extracellular vesicles further exemplifies innovative approaches to improve transplantation outcomes. However, challenges such as MSC heterogeneity and the optimization of therapeutic applications persist. Advanced methodologies, including artificial intelligence (AI) and single-cell RNA sequencing (scRNA-seq), are highlighted as potential technologies for addressing these challenges, potentially steering MSC therapy toward more effective, personalized treatment modalities for diabetes. This review revealed that MSCs are important for advancing diabetes treatment strategies, particularly through islet transplantation. This highlights the importance of MSCs in the field of regenerative medicine, acknowledging both their potential and the challenges that must be navigated to fully realize their therapeutic promise.

Nonwoven fiber meshes for oxygen sensing

Accurate oxygen sensing and cost-effective fabrication are crucial for the adoption of wearable devices inside and outside the clinical setting. Here we introduce a simple strategy to create nonwoven polymeric fibrous mats for a notable contribution towards addressing this need. Although morphological manipulation of polymers for cell culture proliferation is commonplace, especially in the field of regenerative medicine, non-woven structures have not been used for oxygen sensing. We used an airbrush spraying, i.e. solution blowing, to obtain nonwoven fiber meshes embedded with a phosphorescent dye. The fibers serve as a polymer host for the phosphorescent dye and are shown to be non-cytotoxic. Different composite fibrous meshes were prepared and favorable mechanical and oxygen-sensing properties were demonstrated. A Young's modulus of 9.8 MPa was achieved and the maximum oxygen sensitivity improved by a factor of ∼2.9 compared to simple drop cast film. The fibers were also coated with silicone rubbers to produce mechanically robust sensing films. This reduced the sensing performance but improved flexibility and mechanical properties. Lastly, we are able to capture oxygen concentration maps via colorimetry using a smartphone camera, which should offer unique advantages in wider usage. Overall, the introduced composite fiber meshes show a potential to significantly improve cell cultures and healthcare monitoring via absolute oxygen sensing.

Recent Advances in Alginate-Based Hydrogels for Cell Transplantation Applications.

With its exceptional biocompatibility, alginate emerged as a highly promising biomaterial for a large range of applications in regenerative medicine. Whether in the form of microparticles, injectable hydrogels, rigid scaffolds, or bioinks, alginate provides a versatile platform for encapsulating cells and fostering an optimal environment to enhance cell viability. This review aims to highlight recent studies utilizing alginate in diverse formulations for cell transplantation, offering insights into its efficacy in treating various diseases and injuries within the field of regenerative medicine.

Silymarin enriched gelatin methacrylamide bioink imparts hepatoprotectivity to 3D bioprinted liver construct against carbon tetrachloride induced toxicity

Three-dimensional liver bioprinting is an emerging technology in the field of regenerative medicine that aids in the creation of functional tissue constructs that can be used as transplantable organ substitutes. During transplantation, the bioprinted donor liver must be protected from the oxidative stress environment created by various factors during the transplantation procedure, as well as from drug-induced damage from medications taken as part of the post-surgery medication regimen following the procedure. In this study, Silymarin, a flavonoid with the hepatoprotective properties were introduced into the GelMA bioink formulation to protect the bioprinted liver against hepatotoxicity. The concentration of silymarin to be added in GelMA was optimised, bioink properties were evaluated, and HepG2 cells were used to bioprint liver tissue. Carbon tetrachloride (CCl4) was used to induce hepatotoxicity in bioprinted liver, and the effect of this chemical on the metabolic activities of HepG2 cells was studied. The results showed that Silymarin helps with albumin synthesis and shields liver tissue from the damaging effects of CCl4. According to gene expression analysis, CCl4 treatment increased TNF-α and the antioxidant enzyme SOD expression in HepG2 cells while the presence of silymarin protected the bioprinted construct from CCl4-induced damage. Thus, the outcomes demonstrate that the addition of silymarin in GelMA formulation protects liver function in toxic environments.

Versatile Triblock Peptide Self-Assembly System to Mimic Collagen Structure and Function.

The construction of collagen mimetic peptides has been a hot topic in tissue engineering due to their attractive advantages, such as virus-free nature and low immunogenicity. However, all of the reported self-assembled peptides rely on the inclusion of risky elements of potential safety concerns or lack the capability of incorporating critical functional motifs. A versatile self-assembly design of pure synthetic peptides that can mimic the collagen structure and function remains an insurmountably challenging target. We have herein created a type of triblock peptide consisting of a central triple helical block and N-terminal/C-terminal blocks with oppositely charged amino acids. Favorable electrostatic interactions between the two terminal blocks have been demonstrated to trigger the triblock peptides to form collagen-like nanofibers with a distinct D-banding pattern. A length of 3 or above charged amino acid pairs as well as the maintenance of the triple helical conformation are required for the self-assembly of triblock peptides. Notably, integrin and discoidin domain receptor (DDR) binding sequences GFOGER and GVMGFO have been well demonstrated as vivid examples of convenient incorporation of functional motifs into the triblock peptides without interfering with their self-assembly. These triblock peptides provide a robust and versatile strategy to create next-generation peptide-based biomaterials that can recapitulate the structure and function of collagen, which have promising applications in the fields of tissue engineering and regenerative medicine.

Bioactive peptide relieves glucocorticoid-induced osteoporosis by giant macrocyclic encapsulation

Bioactive peptides play a crucial role in the field of regenerative medicine and tissue engineering. However, their application in vivo and clinic is hindered by their poor stability, short half-life, and low retention rate. Herein, we propose a novel strategy for encapsulating bioactive peptides using giant macrocycles. Platelet-derived growth factor (PDGF) bioactive mimicking peptide Nap-FFGVRKKP (P) was selected as the representative of a bioactive peptide. Quaterphen[4]arene (4) exhibited extensive host-guest complexation with P, and the binding constant was (1.16 ± 0.10) × 107 M−1. In vitro cell experiments confirmed that P + 4 could promote the proliferation of BMSCs by 2.27 times. Even with the addition of the inhibitor dexamethasone (Dex), P + 4 was still able to save 76.94% of the cells in the control group. Compared to the Dex group, the bone mass of the mice with osteoporosis in the P + 4 group was significantly increased. The mean trabecular thickness (Tb.Th) increased by 17.03%, and the trabecular bone volume fraction (BV/TV) values increased by 40.55%. This supramolecular bioactive peptide delivery strategy provides a general approach for delivering bioactive peptides and opens up new opportunities for the development of peptide-based drugs.

Therapeutic Applications of Stem Cell-Derived Exosomes.

Exosomes are extracellular vesicles of endosomal origin, ranging from 30 to 150 nm in diameter, that mediate intercellular transfer of various biomolecules, such as proteins, lipids, nucleic acids, and metabolites. They modulate the functions of recipient cells and participate in diverse physiological and pathological processes, such as immune responses, cell-cell communication, carcinogenesis, and viral infection. Stem cells (SCs) are pluripotent or multipotent cells that can differentiate into various cell types. SCs can also secrete exosomes, which exhibit remarkable therapeutic potential for various diseases, especially in the field of regenerative medicine. For example, exosomes derived from mesenchymal stem cells (MSCs) contain proteins, lipids, and miRNAs that can ameliorate endocrine disorders, such as diabetes and cancer. Exosomes from SCs (sc-exos) may offer similar advantages as SCs, but with reduced risks and challenges. Sc-exos have lower tumorigenicity, immunogenicity, and infectivity. They can also deliver drugs more efficiently and penetrate deeper into tissues. In this review, we provide an overview of the recent advances in sc-exos and their therapeutic applications in various diseases, such as diabetes and cancer. We also elucidate how the biological effects of sc-exos depend on their molecular composition. We also address the current challenges and future directions of using sc-exos.

Unlocking the Potential of Stem Cell Microenvironments In Vitro.

The field of regenerative medicine has recently witnessed groundbreaking advancements that hold immense promise for treating a wide range of diseases and injuries. At the forefront of this revolutionary progress are stem cells. Stem cells typically reside in specialized environments in vivo, known as microenvironments or niches, which play critical roles in regulating stem cell behavior and determining their fate. Therefore, understanding the complex microenvironments that surround stem cells is crucial for advancing treatment options in regenerative medicine and tissue engineering applications. Several research articles have made significant contributions to this field by exploring the interactions between stem cells and their surrounding niches, investigating the influence of biomechanical and biochemical cues, and developing innovative strategies for tissue regeneration. This review highlights the key findings and contributions of these studies, shedding light on the diverse applications that may arise from the understanding of stem cell microenvironments, thus harnessing the power of these microenvironments to transform the landscape of medicine and offer new avenues for regenerative therapies.

Directed differentiation of human embryonic stem cells into parathyroid cells and establishment of parathyroid organoids.

Differentiation of human embryonic stem cells (hESCs) into human embryonic stem cells-derived parathyroid-like cells (hESC-PT) has clinical significance in providing new therapies for congenital and acquired parathyroid insufficiency conditions. However, a highly reproducible, well-documented method for parathyroid differentiation remains unavailable. By imitating the natural process of parathyroid embryonic development, we proposed a new hypothesis about the in vitro differentiation of parathyroid-like cells. Transcriptome, differentiation marker protein detection and parathyroid hormone (PTH) secretion assays were performed after the completion of differentiation. To optimize the differentiation protocol and further improve the differentiation rate, we designed glial cells missing transcription factor 2 (GCM2) overexpression lentivirus transfection assays and constructed hESCs-derived parathyroid organoids. The new protocol enabled hESCs to differentiate into hESC-PT. HESC-PT cells expressed PTH, GCM2 and CaSR proteins, low extracellular calcium culture could stimulate hESC-PT cells to secrete PTH. hESC-PT cells overexpressing GCM2 protein secreted PTH earlier than their counterpart hESC-PT cells. Compared with the two-dimensional cell culture environment, hESCs-derived parathyroid organoids secreted more PTH. Both GCM2 lentiviral transfection and three-dimensional cultures could make hESC-PT cells functionally close to human parathyroid cells. Our study demonstrated that hESCs could differentiate into hESC-PT in vitro, which paves the road for applying the technology to treat hypoparathyroidism and introduces new approaches in the field of regenerative medicine.

Industry updates from the field of stem cell research and regenerative medicine in January 2024.

Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from nonacademic institutions in January 2024.

Comparison of the osteogenic potential of fibroblasts from different sources

ObjectiveWith the growing interest in the role of fibroblasts in osteogenesis, this study presents a comparative evaluation of the osteogenic potential of fibroblasts derived from three distinct sources: human gingival fibroblasts (HGFs), mouse embryonic fibroblasts (NIH3T3 cells), and mouse subcutaneous fibroblasts (L929 cells). MC3T3-E1 pre-osteoblast cells were employed as a positive control for osteogenic behavior. DesignOur assessment involved multiple approaches, including vimentin staining for cell origin verification, as well as ALP and ARS staining in conjunction with RT-PCR for osteogenic characterization. ResultsOur findings revealed the superior osteogenic differentiation capacity of HGFs compared to MC3T3-E1 and NIH3T3 cells. Analysis of ALP staining confirmed that early osteogenic differentiation was most prominent in MC3T3-E1 cells at 7 days, followed by NIH3T3 and HGFs. However, ARS staining at 21 days demonstrated that HGFs produced the highest number of calcified nodules, indicating their robust potential for late-stage mineralization. This late-stage osteogenic potential of HGFs was further validated through RT-PCR analysis. In contrast, L929 cells displayed no significant osteogenic differentiation potential. ConclusionsIn light of these findings, HGFs emerge as the preferred choice for seed cells in bone tissue engineering applications. This study provides valuable insights into the potential utility of HGFs in the fields of bone tissue engineering and regenerative medicine.

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.

ADVANCES IN BIOTECHNOLOGY FOR CELLULAR AND TISSUE REGENERATION: CHALLENGES AND PERSPECTIVES IN HUMAN DISEASE TREATMENT

Biotechnology constitutes a realm of inquiry that extends its benefits across diverse domains of knowledge, ranging from agricultural sciences to clinical applications. This field leverages technology to address challenges frequently entailing living organisms. Of current significance is the endeavor to elucidate the process of animal regeneration, particularly within the human species, given its burgeoning potential as an ally in the treatment and cure of various maladies. Recognizing the societal importance of this subject, the present article seeks to expound upon contemporary biotechnological advancements facilitating the exploration of cellular and tissue regeneration for the treatment of human diseases. To this end, a comprehensive review of articles delineating the current landscape was conducted, involving a comparative analysis of regenerative activity across species, with a specific focus on humans. Evidentially, the use of biomaterials in tissue regeneration assumes paramount importance, albeit not without the formidable challenge posed by the inflammatory process. Stem cells, conversely, present themselves as promising entities in the realm of regeneration. However, their interaction within the host organism necessitates further scrutiny to attain a more nuanced understanding. Despite strides made in the field of regenerative medicine, the lack of comprehensive comprehension regarding the properties of biomaterials and their responses within the human body constrains their clinical applicability. Nevertheless, an auspicious future is envisioned, marked by advancements in biomaterials and a heightened understanding of interactions within the human body, thereby fostering the development of more efficacious treatments for a myriad of diseases.

Bibliometric analysis of organoids in regenerative medicine-related research worldwide over two decades (2002-2022).

Aim: This study aimed to evaluate the trends in organoid culture research within the field of regenerative medicine from 2002 to 2022. Methods: The worldwide distribution of organoid research in regenerative medicine articles indexed in the Scopus database was analyzed. Result: A total of 840 documents were analyzed, averaging 42 publications annually. The USA (n=296) led in publications, followed by China (n=127), Japan (n=91) and the UK (n=75). Since 2011, research has surged, particularly in China, which emerged as a prominent center. Conclusion: The findings highlight significant growth in organoid research, promising future organ transplantation. Research trends integrate tissue engineering, gene modification and induced pluripotent stem cell technologies, reflecting a move toward personalized medicine.

The development and application of stem cells in biomedicine

Over the past few decades, significant advancements have been made in the field of stem cell research. Through the utilization of a literature review methodology, our study delved into an examination of three fundamental sources of stem cells, their respective activities, and the possible therapeutic applications of stem cells within the field of regenerative medicine. Furthermore, the discourse around ethical concerns pertaining to stem cell research is examined, while existing literature is consulted to identify the regulatory frameworks governing the lawful execution of embryonic stem cell research. The investigation of stem cells in the field of regenerative medicine holds significant potential for advancing human welfare. Stem cells have the capacity to replace outmoded therapy modalities, thereby offering improved alternatives. Furthermore, several diseases that were previously deemed incurable have now become viable candidates for treatment through the application of stem cell research. This research on stem cells has a dual purpose: advancing the field of regenerative medicine and deepening our understanding of life, enabling us to witness the successive wonders of existence.

An overview of nasal cartilage bioprinting: from bench to bedside.

Nasal cartilage diseases and injuries are known as significant challenges in reconstructive medicine, affecting a substantial number of individuals worldwide. In recent years, the advent of three-dimensional (3D) bioprinting has emerged as a promising approach for nasal cartilage reconstruction, offering potential breakthroughs in the field of regenerative medicine. This paper provides an overview of the methods and challenges associated with 3D bioprinting technologies in the procedure of reconstructing nasal cartilage tissue. The process of 3D bioprinting entails generating a digital 3D model using biomedical imaging techniques and computer-aided design to integrate both internal and external scaffold features. Then, bioinks which consist of biomaterials, cell types, and bioactive chemicals, are applied to facilitate the precise layer-by-layer bioprinting of tissue-engineered scaffolds. After undergoing in vitro and in vivo experiments, this process results in the development of the physiologically functional integrity of the tissue. The advantages of 3D bioprinting encompass the ability to customize scaffold design, enabling the precise incorporation of pore shape, size, and porosity, as well as the utilization of patient-specific cells to enhance compatibility. However, various challenges should be considered, including the optimization of biomaterials, ensuring adequate cell viability and differentiation, achieving seamless integration with the host tissue, and navigating regulatory attention. Although numerous studies have demonstrated the potential of 3D bioprinting in the rebuilding of such soft tissues, this paper covers various aspects of the bioprinted tissues to provide insights for the future development of repair techniques appropriate for clinical use.