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Generation of induced pluripotent stem cells (iPSCs) and their differentiation into mesenchymal stem/stromal cells (iMSCs) have created exciting source of cells for autologous therapy. In this study, we have compared the therapeutic potential of iMSCs generated from urinary epithelial (UE) cells with the available umbilical cord MSCs (UC‐MSCs). For this, adult UE cells were treated with the mRNA of pluripotent genes (OCT4, NANOG, SOX2, KLF4, MYC and LIN28) and a cocktail of miRNAs under specific culture conditions for generating iPSCs. Our non‐viral and mRNA‐based treatment regimen demonstrated a high reprogramming efficiency to about 30% at passage 0. These UE‐iPSCs were successfully differentiated further into ectoderm, endoderm and mesoderm lineage of cells. Moreover, these UE‐iPSCs were subsequently differentiated into iMSCs and were compared with the UC‐MSCs. These iMSCs were capable of differentiating into osteocytes, chondrocytes and adipocytes. Our qRT‐PCR and Western blot data showed that the CD73, CD90 and CD105 gene transcripts and proteins were highly expressed in iMSCs and UC‐MSCs but not in other cells. The comparative qRT‐PCR data showed that the iMSCs maintained their MSC characteristics without any chromosomal abnormalities even at later passages (P15), during which the UC‐MSCs started losing their MSC characteristics. Importantly, the wound‐healing property demonstrated through migration assay was superior in iMSCs when compared to the UC‐MSCs. In this study, we have demonstrated an excellent non‐invasive and pain‐free method of obtaining iMSCs for regenerative therapy. These homogeneous autologous highly proliferative iMSCs may provide an alternative source of cells to UC‐MSCs for treating various diseases.

Mesenchymal stem cells (MSCs) are multipotent cells which can proliferate and replace dead cells in the body. MSCs also secrete immunomodulatory molecules, creating a regenerative microenvironment that has an excellent potential for tissue regeneration. MSCs can be easily isolated and grown in vitro for various applications. For the past two decades, MSCs have been used in research, and many assays and tests have been developed proving that MSCs are an excellent cell source for therapy. This review focusses on quality control parameters required for applications of MSCs including colony formation, surface markers, differentiation potentials, and telomere length. Further, the specific mechanisms of action of MSCs under various conditions such as trans-differentiation, cell fusion, mitochondrial transfer, and secretion of extracellular vesicles are discussed. This review aims to underline the applications and benefits of MSCs in regenerative medicine and tissue engineering.

Characterization of cardiomyocyte beat patterns is needed for quality control of cells intended for surgical injection as well as to establish phenotypes in disease modeling or toxicity studies. Optical-flow based analysis of videomicroscopic recordings offer a manipulation-free and efficient characterization of contractile cycles, an important characteristics of cardiomyocyte phenotype. We demonstrate that by appropriate computational analysis of optical flow data one can identify distinct contractile centers and distinguish active cell contractility from passive elastic tissue deformations. Our proposed convergence measure correlates with myosin IIa immuno-localization and is capable to resolve contractile waves and their synchronization within maturing, unlabeled induced pluripotent stem cell-derived cardiomyocyte cultures.

Bone integrity is maintained through continuous remodeling, orchestrated by the coordinated actions of osteocytes, osteoblasts, and osteoclasts. Once considered passive bystanders, osteocytes are now recognized as central regulators of this process, mediating biochemical signaling and mechanotransduction. Malfunctioning osteocytes contribute to serious skeletal disorders such as osteoporosis. Mesenchymal stromal cells (MSCs), multipotent stem cells capable of differentiating into osteoblasts, have emerged as promising agents for bone regeneration, primarily through the paracrine effects of their secreted exosomes. MSC-derived exosomes are nanoscale vesicles enriched with proteins, lipids, and nucleic acids that promote intercellular communication, osteoblast proliferation and differentiation, and angiogenesis. Notably, they deliver osteoinductive microRNAs (miRNAs) that influence osteogenic markers and support bone tissue repair. In vivo investigations validate their capacity to enhance bone regeneration, increase bone volume, and improve biomechanical strength. Additionally, MSC-derived exosomes regulate the immune response, creating pro-osteogenic and pro-angiogenic factors, boosting their therapeutic efficacy. Due to their cell-free characteristics, MSC-derived exosomes offer benefits such as diminished immunogenicity and minimal risk of off-target effects. These properties position them as promising and innovative approaches for bone regeneration, integrating immunomodulatory effects with tissue-specific regenerative capabilities.

Diseases of the preterm newborn such as bronchopulmonary dysplasia, necrotizing enterocolitis, cerebral palsy, and hypoxic-ischemic encephalopathy continue to be major causes of infant mortality and long-term morbidity. Effective therapies for the prevention or treatment for these conditions are still lacking as recent clinical trials have shown modest or no benefit. Stem cell therapy is rapidly emerging as a novel therapeutic tool for several neonatal diseases with encouraging pre-clinical results that hold promise for clinical translation. However, there are a number of unanswered questions and facets to the development of stem cell therapy as a clinical intervention. There is much work to be done to fully elucidate the mechanisms by which stem cell therapy is effective (e.g., anti-inflammatory versus pro-angiogenic), identifying important paracrine mediators, and determining the timing and type of therapy (e.g., cellular versus secretomes), as well as patient characteristics that are ideal. Importantly, the interaction between stem cell therapy and current, standard-of-care interventions is nearly completely unknown. In this review, we will focus predominantly on the use of mesenchymal stromal cells for neonatal diseases, highlighting the promises and challenges in clinical translation towards preventing neonatal diseases in the 21st century.

Human induced pluripotent stem cells (iPSCs) derived cardiomyocytes (iCMCs) would provide an unlimited cell source for regenerative medicine and drug discoveries. The objective of our study is to generate functional cardiomyocytes from human iPSCs and to develop a novel method of measuring contractility of CMCs. In a series of experiments, adult human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVECs) were treated with a combination of pluripotent gene DNA and mRNA under specific conditions. The iPSC colonies were identified and differentiated into various cell lineages, including CMCs. The contractile activity of CMCs was measured by a novel method of frame-by-frame cross correlation (particle image velocimetry-PIV) analysis. Our treatment regimen transformed 4% of HSFs into iPSC colonies at passage 0, a significantly improved efficiency compared with use of either DNA or mRNA alone. The iPSCs were capable of differentiating both in vitro and in vivo into endodermal, ectodermal and mesodermal cells, including CMCs with >88% of cells being positive for troponin T (CTT) and Gata4 by flow cytometry. We report a highly efficient combination of DNA and mRNA to generate iPSCs and functional iCMCs from adult human cells. We also report a novel approach to measure contractility of iCMCs.

Mesenchymal stem/stromal cells (MSC) are well known for immunomodulation; however, the mechanisms involved in their benefits in the ischemic retina are unknown. This study tested the hypothesis that MSC induces upregulation of transcription factor forkhead box protein P3 (Foxp3) in T cells to elicit immune modulation, and thus, protect against retinal damage. Induced MSCs (iMSCs) were generated by differentiating the induced pluripotent stem cells (iPSC) derived from urinary epithelial cells through a noninsertional reprogramming approach. In in-vitro cultures, iMSC transferred mitochondria to immune cells via F-actin nanotubes significantly increased oxygen consumption rate (OCR) for basal respiration and ATP production, suppressed effector T cells, and promoted differentiation of CD4+CD25+ T regulatory cells (Tregs) in coculture with mouse splenocytes. In in-vivo studies, iMSCs transplanted in ischemia-reperfusion (I/R) injured eye significantly increased Foxp3+ Tregs in the retina compared to that of saline-injected I/R eyes. Furthermore, iMSC injected I/R eyes significantly decreased retinal inflammation as evidenced by reduced gene expression of IL1β, VCAM1, LAMA5, and CCL2 and improved b-wave amplitudes compared to that of saline-injected I/R eyes. Our study demonstrates that iMSCs can transfer mitochondria to immune cells to suppress the effector T cell population. Additionally, our current data indicate that iMSC can enhance differentiation of T cells into Foxp3 Tregs in vitro and therapeutically improve the retina’s immune function by upregulation of Tregs to decrease inflammation and reduce I/R injury-induced retinal degeneration in vivo.

Cardiac injury, such as myocardial infarction and heart failure, remains a significant global health burden. The limited regenerative capacity of the adult heart poses a challenge for restoring its function after injury. Mesenchymal stem cells (MSCs) have emerged as promising candidates for cardiac regeneration due to their ability to differentiate into various cell types and secrete bioactive molecules. In recent years, attention has been given to noncoding RNAs derived from MSCs, particularly long noncoding RNAs (lncRNAs), and their potential role in cardiac injury and repair. LncRNAs are RNA molecules that do not encode proteins but play critical roles in gene regulation and cellular responses including cardiac repair and regeneration. This review focused on MSC-derived lncRNAs and their implications in cardiac regeneration, including their effects on cardiac function, myocardial remodeling, cardiomyocyte injury, and angiogenesis. Understanding the molecular mechanisms of MSC-derived lncRNAs in cardiac injury and repair may contribute to the development of novel therapeutic strategies for treating cardiovascular diseases. However, further research is needed to fully elucidate the potential of MSC-derived lncRNAs and address the challenges in this field.

Graphene and its related nanocomposites have garnered significant interest due to their distinct physiochemical and biological properties. In this study, reduced graphene oxide–silver hybrid nanostructures were synthesized for applications in biomedical nanotechnology, particularly in targeting cancer stem cells (CSCs). A range of analytical techniques, such as X-ray diffraction (XRD), Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and UV–visible absorption spectroscopy (UV–VIS), were employed to characterize graphene oxide (GO), reduced graphene oxide (rGO)–silver nanoparticles (AgNPs), and their composite structures. The GO-rGO-AgNPs exhibited potent anticancer properties as evidenced by cell culture assays, spheroid formation assay, and quantitative RT-PCR analysis. Treatment of breast cancer cells (MCF-7) with GO, rGO, and AgNPs significantly reduced cell proliferation and mammosphere formation. Furthermore, these treatments downregulated the expression of marker genes associated with CSCs in MCF-7 cells. Among the tested materials, rGO-AgNP, sodium citrate-mediated GO-AgNP, and rGO-AgNP nanocomposites demonstrated superior inhibitory effects on cell survival compared to GO alone. These findings suggest that these nanocomposites hold promise as effective and non-toxic therapeutic agents for targeting cancer cells and CSCs, thereby offering a novel approach to cancer treatment.

Drug resistance has been a major obstacle in the quest for a cancer cure. Many chemotherapeutic treatments fail to overcome chemoresistance, resulting in tumor remission. The exact process that leads to drug resistance in many cancers has not been fully explored or understood. However, the discovery of RNA binding proteins (RBPs) has provided insight into various pathways and post-transcriptional gene modifications involved in drug tolerance. RBPs are evolutionarily conserved proteins, and their abnormal gene expression has been associated with cancer progression. Additionally, RBPs are aberrantly expressed in numerous neoplasms. RBPs have also been implicated in maintaining cancer stemness, epithelial-to-mesenchymal transition, and other processes. In this review, we aim to provide an overview of RBP-mediated mechanisms of drug resistance and their implications in cancer malignancy. We discuss in detail the role of major RBPs and their correlation with noncoding RNAs (ncRNAs) that are associated with the inhibition of chemosensitivity. Understanding and exploring the pathways of RBP-mediated chemoresistance will contribute to the development of improved cancer diagnosis and treatment strategies.