Where Are We Now and Where Is Cell Therapy Headed? (2nd Edition)

Dear Colleagues,

The field of cell therapy is at a critical inflection point. While the early promise of using living cells to repair and regenerate tissues has led to remarkable clinical achievements, the scientific community is now embracing a more refined and powerful paradigm. A fundamental shift is taking place: moving from viewing the cell as the sole therapeutic agent to harnessing its biological outputs—such as the secretome and extracellular vesicles (EVs)—as next-generation tools for therapy. This transition from cell transplantation to cell-free and bio-inspired therapeutics offers new opportunities to overcome key challenges in manufacturing, safety, and efficacy.

This Special Issue aims to reflect this exciting evolution by gathering contributions that bridge fundamental biology with innovative clinical translation. We seek to highlight the strategies that are reshaping regenerative medicine and immunotherapy, from the complexity of stem-cell niches to the precision engineering of cellular and cell-derived products.

We welcome original research articles and comprehensive review papers that explore bold and forward-looking concepts in this rapidly advancing field. Our goal is to create a landmark volume that will serve as a valuable resource for scientists and clinicians alike.

Areas of particular interest include, but are not limited to:

• Investigations into the therapeutic efficacy of mesenchymal stromal cells (MSCs), pluripotent stem cells, and their bioactive derivatives (e.g., secretomes, purified EVs) across diverse disease models.
• Studies exploring how altered stem-cell niches contribute to pathology, and how advanced therapies can restore tissue homeostasis and function.
• Innovative platforms for cell and gene therapy in monogenic, degenerative, and malignant diseases, with emphasis on improving safety, control, and therapeutic potency.
• Design, application, and mechanistic insights into next-generation CAR-T, CAR-NK, and other engineered immune cells for the treatment of hematological and solid tumors.
• Novel uses of engineered MSCs or other cell types as "smart" delivery vehicles for targeted therapeutic payloads, including drugs, genes, or nanoparticles.

Dr. Andrea Papait
Dr. Paola Chiodelli
Guest Editors

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