Off-the-shelf, engineered non-living stem cell strategy for advancing cellular therapies
Tiep Tien Nguyen # 1, Nhu-Nam Nguyen # 1, Linh Nguyen # 1, Kim-Phuong Phan 1, Junhyeung Park 1, Jong-Hyuk Sung 2, Simmyung Yook 3 4, Hu-Lin Jiang 5, Jee-Heon Jeong 6
Nature Biomedical Engineering
Non-living cell therapeutics have become crucial for treating diverse disease conditions. However, ineffective manufacturing processes, significant cellular content loss and structural damage reduce therapeutic efficacy. Here we present a translational approach for designing ‘off-the-shelf’ highly efficient active lyophilized tannic-acid-engineered non-living cells (HealTEC) with distinct features. Our strategy is customizable and integrates cellular function enhancement, high-dose tannic acid-induced cell inactivation, low-temperature cellular matter condensation and advanced lyophilization. By leveraging it, we engineer mesenchymal stem cell-derived HealTEC as a bio-reservoir platform, enabling formulations enriched in immunomodulatory factors for ulcerative colitis, enriched in angiogenic factors for hindlimb ischaemia or loaded with drug nanoparticles for asthma. Importantly, the HealTEC formulations exhibit high therapeutic stability after long-term storage at mild conditions. Furthermore, HealTEC injections induce much lower immunogenicity than living cell injections, both in the short term and long term. HealTEC technology presents the potential for upscaling cell manufacture, commercialization and reshaping worldwide clinical demands. This paper was published in Nature Biomedical Engineering (IF: 26.3 (2025), and 32.6 (5-year)) in June 2026 (Tiep Tien Nguyen et al., https://doi.org/10.1038/s41551-026-01697-5) and was highlighted in News & Views (Nature Biomedical Engineering) (https://doi.org/10.1038/s41551-026-01729-0).