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Key Points This Review describes recent progress in directing human pluripotent stem cells (hPSCs) into specific progeny that could have therapeutic purposes for a range of diseases. It also addresses major hurdles in the transition of hPSC-based cell therapies from the bench to the bedside. Neural induction of hPSCs can be achieved in several ways. Recent protocols use defined neural inducers — such as inhibitors of transforming growth factor-β (TGFβ) and bone morphogenetic protein (BMP) (that is, dual SMAD inhibition) — to greatly enhance the efficiency and the speed of neural induction. The derivation of dopamine neurons from hPSCs has been achieved a decade ago, but the cells did not show good engraftment. Recent data shows that those neurons lacked expression of forkhead box protein A2 (FOXA2), which is a DNA-binding transcription factor that is fundamental for authentic midbrain identity. A novel protocol derives dopamine neurons through a floor plate intermediate, which show genetic, biochemical and physiological features of authentic midbrain neurons. They also survive and ameliorate Parkinson's disease-like behaviour in vivo . Improved protocols for the derivation of medium spiny striatal neurons from hPSCs has been reported, and evidence shows survival and behavioural improvement in a lesion model of Huntington's disease. The derivation of glial cells from hPSCs is faced with the challenge of protracted developmental timing in vitro , which is similar to the in vivo situation. The derivation of oligodendrocytes has been achieved using long-term in vitro cultures; these cells have been grafted in neonatal Shiverer -expressing mice with good cell survival, remyelination and extended lifespan in these mice. The current derivation of non-neural cell types — such as cardiomyocytes, pancreatic islet cells and engraftable haematopoietic stem cells — faces substantial challenges owing to the immature nature of the differentiated cells (for cardiomyocytes), the need for in vivo differentiation (for pancreatic islet cells) and poor in vivo homing (for haematopoietic stem cells). New developments in cell differentiation include the use of potent small molecules that allow the direct manipulation of multiple signalling pathways and, in some cases, the acceleration of differentiation timelines. Other approaches include cell purification and three-dimensional cultures that harness the self-organizing potential of hPSC-derived lineages. Defining cell identity in vitro is a fundamental element in designing directed differentiation strategies and includes expression of cell type-specific markers, transcriptional profiles and assessments of the epigenetic or enhancer landscapes. Assessment of in vivo function includes electrophysiology, the use of genetically encoded calcium sensors, microdialysis and optogenetic techniques, as well as behavioural studies. Autologous cell sources, such as patient-derived induced pluripotent stem cells, are of great interest but currently face substantial hurdles for clinical implementation that are related to safety and regulatory requirements. The translation of direct reprogramming and nuclear transfer strategies are in early stages of development. A spinal cord trial using human embryonic stem cell (hESC)-derived oligodendrocytes has not reported any major adverse effects, although the trial has been abandoned. Ongoing clinical trials using hESC-derived retinal pigment epithelial in eye repair are promising. The derivation of disease-relevant cell types from pluripotent stem cells holds much promise for disease therapy. The recent progress in directed differentiation and the challenges ahead are discussed in this Review. After years of incremental progress, several recent studies have succeeded in deriving disease-relevant cell types from human pluripotent stem cell (hPSC) sources. The prospect of an unlimited cell source, combined with promising preclinical data, indicates that hPSC technology may be on the verge of clinical translation. In this Review, we discuss recent progress in directed differentiation, some of the new technologies that have facilitated the success of hPSC therapies and the remaining hurdles on the road towards developing hPSC-based cell therapies.

Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine. This review summarizes the recent progress of particular mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs. We focused on discussing the functional roles of paracrine activities, direct cell–cell contact, mitochondrial transfer, and extracellular vesicles related to MSC-mediated effects on immune cell responses, cell survival, and regeneration. This will provide an overview of the current research on the rapid development of MSC-based therapies.

Hydrogels from different materials can be used in biomedical field as an innovative approach in regenerative medicine. Depending on the origin source, hydrogels can be synthetized through chemical and physical methods. Hydrogel can be characterized through several physical parameters, such as size, elastic modulus, swelling and degradation rate. Lately, research is focused on hydrogels derived from biologic materials. These hydrogels can be derived from protein polymers, such as collage, elastin, and polysaccharide polymers like glycosaminoglycans or alginate among others. Introduction of decellularized tissues into hydrogels synthesis displays several advantages compared to natural or synthetic based hydrogels. Preservation of natural molecules such as growth factors, glycans, bioactive cryptic peptides and natural proteins can promote cell growth, function, differentiation, angiogenesis, anti-angiogenesis, antimicrobial effects, and chemotactic effects. Versatility of hydrogels make possible multiple applications and combinations with several molecules on order to obtain the adequate characteristic for each scope. In this context, a lot of molecules such as cross link agents, drugs, grow factors or cells can be used. This review focuses on the recent progress of hydrogels synthesis and applications in order to classify the most recent and relevant matters in biomedical field.

Background Extracellular vesicles (EVs) have been considered promising tools in regenerative medicine. However, the nanoscale properties of EVs make them sensitive to environmental conditions. Optimal storage protocols are crucial for maintaining EV structural, molecular, and functional integrity. This systematic review aimed to gather evidence on the effects of various storage protocols on EV characteristics and integrity. Strategy A comprehensive search was conducted for original studies investigating the impacts of storage temperature, freezing techniques, freeze-thaw cycles, and stabilizing strategies on EV concentration, size distribution, morphology, cargo content, and bioactivity. Results from 50 included studies were analyzed. Results Data indicated that rapid freezing procedures and constant subzero temperatures (optimally − 80 °C) resulted in appropriate EV quantity and cargo preservation. Subjecting EVs to multiple freeze-thaw cycles decreased particle concentrations, RNA content, impaired bioactivity, and increased EV size and aggregation. Electron microscopy revealed vesicle enlargement, and fusion, along with membrane deformation after being exposed to substandard storage protocols. The addition of stabilizers like trehalose helped EVs to maintain integrity. Of note, storage in native biofluids offered improved stability over purified EVs in buffers. Conclusion Data emphasize the critical need for precise storage protocols for EVs to ensure reproducible research outcomes and clinical applications. Further studies using reliable methods are necessary to create specific guidelines for improving the stability of EVs in various applications.