Mesenchymal stem/stromal cells (MSCs) have garnered attention for their potential in cancer therapy due to their ability to home to tumor sites. Engineered MSCs have been developed to deliver therapeutic proteins, microRNAs, prodrugs, chemotherapy drugs, and oncolytic viruses directly to the tumor microenvironment, with the goal of enhancing therapeutic efficacy while minimizing off-target effects. Despite promising results in preclinical studies and clinical trials, challenges such as variability in delivery efficiency and safety concerns persist. Ongoing research aims to optimize MSC-based cancer eradication and immunotherapy, enhancing their specificity and efficacy in cancer treatment. This review focuses on advancements in engineering MSCs for tumor-targeted therapy.

Nicotinamide adenine dinucleotide (NAD⁺) is a critical metabolite that acts as a cofactor in energy metabolism, and serves as a cosubstrate for non-redox NAD⁺-dependent enzymes, including sirtuins, CD38 and poly(ADP-ribose) polymerases. NAD⁺metabolism can regulate functionality attributes of innate and adaptive immune cells and contribute to inflammatory responses. Thus, the manipulation of NAD⁺bioavailability can reshape the courses of immunological diseases. Here, we review the basics of NAD⁺biochemistry and its roles in the immune response, and discuss current challenges and the future translational potential of NAD⁺research in the development of therapeutics for inflammatory diseases, such as COVID-19.

Nicotinamide adenine dinucleotide (NAD⁺) is a critical coenzyme involved in cellular metabolism, energy balance, and various physiological processes. Nicotinamide phosphoribosyltransferase (NAMPT) is a key rate-limiting enzyme in NAD⁺ synthesis, regulating the NAD⁺ regeneration pathway. This review summarizes the multiple roles of NAMPT in both physiological and pathological states, particularly in cellular stress, aging, metabolic disorders, and cancer. We first describe the central role of NAMPT in NAD⁺ synthesis and explore how NAD⁺ levels are regulated through NAMPT to control cellular functions and metabolic adaptation. Second, we analyze the pathological roles of NAMPT in aging and related diseases, highlighting how NAD⁺ depletion leads to mitochondrial dysfunction, DNA damage, and immune system dysregulation. Notably, NAMPT exacerbates cancer immune evasion mechanisms by influencing immune cell functions and the metabolic environment of tumors. We also discuss the potential of NAMPT as a therapeutic target, particularly through NAD⁺ precursor supplementation or the use of NAMPT activators and inhibitors to modulate NAD⁺ metabolism in aging, metabolic diseases, and cancer. Future research should focus on exploring the functional differences of NAMPT in various tissues and its therapeutic potential in disease treatment.

Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a crucial coactivator that regulates mitochondrial biogenesis and fu

Skeletal muscle has an extraordinary regenerative capacity reflecting the rapid activation and effective differentiation of muscle stem cells (MuSCs). In the course of muscle regeneration, MuSCs are reprogrammed by immune cells. In turn, MuSCs confer immune cells anti-inflammatory properties to resolve inflammation and facilitate tissue repair. Indeed, MuSCs can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory ability, including effects primed by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). At the molecular level, the tryptophan metabolites, kynurenine or kynurenic acid, produced by indoleamine 2,3-dioxygenase (IDO), augment the expression of TNF-stimulated gene 6 (TSG6) through the activation of the aryl hydrocarbon receptor (AHR). In addition, insulin growth factor 2 (IGF2) produced by MuSCs can endow maturing macrophages oxidative phosphorylation (OXPHOS)-dependent anti-inflammatory functions. Herein, we summarize the current understanding of the immunomodulatory characteristics of MuSCs and the issues related to their potential applications in pathological conditions, including COVID-19.