Off‑the‑shelf, engineered non-living stem cell strategy for advancing cellular therapies.

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.