n regulating neutrophil infiltration while increasing levels of anti-inflammatory M2 macrophages and reduces the number of apoptotic cells. Therefore, the multifunctional properties of the developed AgNP thermo-responsive hydrogel offers great clinical potential to control bacterial infections and promote wound healing.Injectable thermosensitive hydrogels are free-flowing polymer solutions at low or room temperature, making them easy to encapsulate the therapeutic payload or cells via simply mixing. Upon injection into the body, in situ forming hydrogels triggered by body temperature can act as drug-releasing reservoirs or cell-growing scaffolds. Finally, the hydrogels are eliminated from the administration sites after they accomplish their missions as depots or scaffolds. This review outlines the recent progress of poly(ethylene glycol) (PEG)-based biodegradable thermosensitive hydrogels, especially those composed of PEG-polyester copolymers, PEG-polypeptide copolymers and poly(organophosphazene)s. The material design, performance regulation, thermogelation and degradation mechanisms, and corresponding applications in the biomedical field are summarized and discussed. A perspective on the future thermosensitive hydrogels is also highlighted. STATEMENT OF SIGNIFICANCE Thermosensitive hydrogels undergoing reversible sol-to-gel phase transitions in response to temperature variations are a class of promising biomaterials that can serve as minimally invasive injectable systems for various biomedical applications. Hydrophilic PEG is a main component in the design and fabrication of thermoresponsive hydrogels due to its excellent biocompatibility. By incorporating hydrophobic segments, such as polyesters and polypeptides, into PEG-based systems, biodegradable and thermosensitive hydrogels with adjustable properties in vitro and in vivo have been developed and have recently become a research hotspot of biomaterials. The summary and discussion on molecular design, performance regulation, thermogelation and degradation mechanisms, and biomedical applications of PEG-based thermosensitive hydrogels may offer a demonstration of blueprint for designing new thermogelling systems and expanding their application scope.Mesenchymal stromal cells (MSCs) have gained immense attention over the past two decades due to their multipotent differentiation potential and pro-regenerative and immunomodulatory cytokine secretory profiles. Their ability to modulate the host immune system and promote tolerance has prompted several allogeneic and autologous hMSC-based clinical trials for the treatment of graft-versus-host disease and several other immune-induced disorders. However, clinical success beyond safety is still controversial and highly variable, with inconclusive therapeutic benefits and little mechanistic explanation. This clinical variability has been broadly attributed to inconsistent MSC sourcing, phenotypic characterization, variable potency, and non-standard isolation protocols, leading to functional heterogeneity among administered MSCs. Homogeneous MSC populations are proposed to yield more predictable, reliable biological responses and clinically meaningful properties relevant to cell-based therapies. Limited comparisons of heterogeneous MSCs with homogenous MSCs are reported. This review addresses this gap in the literature with a critical analysis of strategies aimed at decreasing MSC heterogeneity concerning their reported immunomodulatory profiles. STATEMENT OF SIGNIFICANCE This review collates, summarizes, and critically analyzes published strategies that seek to improve homogeneity in immunomodulatory functioning MSC populations intended as cell therapies to treat immune-based disorders, such as graft-vs-host-disease. No such review for MSC therapies, immunomodulatory profiles and cell heterogeneity analysis is published. Since MSCs represent the most clinically studied experimental cell therapy platform globally for which there remains no US domestic marketing approval, insights into MSC challenges in therapeutic product development are imperative to providing solutions for immunomodulatory variabilities.Tumor immunotherapy is rapidly evolving as one of the major pillars of cancer treatment. Cell-based immunotherapies, which utilize patient’s own immune cells to eliminate cancer cells, have shown great promise in treating a range of malignancies, especially those of hematopoietic origins. However, their performance on a broader spectrum of solid tumor types still fall short of expectations in the clinical stage despite promising preclinical assessments. In this review, we briefly introduce cell-based immunotherapies and the inhibitory mechanisms in tumor microenvironments that may have contributed to this discrepancy. Specifically, a major obstacle to the clinical translation of cell-based immunotherapies is in the lack of preclinical models that can accurately assess the efficacies and mechanisms of these therapies in a (patho-)physiologically relevant manner. Lately, tissue engineering and organ-on-a-chip tools and microphysiological models have allowed for more faithful recapitulation of the tumor microenvithful recapitulation of TME for cell-based immunotherapies, and some key considerations for the future development of engineered tumor models. This overview will provide a better understanding on the role of engineered models in accelerating immunotherapeutic discoveries and clinical translations.Parkinson’s disease (PD) is a common neurodegenerative disease characterized by a progressive loss of fine motor function that impacts 1-2 out of 1,000 people. PD occurs predominately late in life and lacks a definitive biomarker for early detection. Recent cross-disciplinary progress has implicated the gut as a potential origin of PD pathogenesis. The gut-origin hypothesis has motivated research on gut PD pathology and transmission to the brain, especially during the prodromal stage (10-20 years before motor symptom onset). this website Early findings have revealed several possible triggers for Lewy pathology – the pathological hallmark of PD – in the gut, suggesting that microbiome and epithelial interactions may play a greater than appreciated role. But the mechanisms driving Lewy pathology and gut-brain transmission in PD remain unknown. Development of artificial α-Synuclein aggregates (α-Syn preformed fibrils) and animal disease models have recapitulated features of PD progression, enabling for the first time, controlled investigation of the gut-origin hypothesis.