Adipose-Derived Stem Cells in Ophthalmic Regenerative Medicine: From Cell Replacement to Precision Engineering.

Abstract

Adipose‑derived stem cells (ASCs) have emerged as a promising cell source in ophthalmic regenerative medicine, attributed to their accessibility, differentiation potential, and paracrine functions. Despite compelling preclinical evidence, clinical outcomes remain unsatisfactory. Departing from the conventional disease‑oriented categorization, this review adopts the cognitive evolution of ASC therapeutic mechanisms as its organizational thread, synthesizing evidence from 158 studies across six ophthalmic subspecialties. Four sequential paradigms are identified: (1) multilineage differentiation and cell replacement; (2) paracrine signaling and microenvironmental modulation; (3) extracellular vesicles and cell‑free therapy; and (4) engineering modifications and precision delivery. Cross‑disciplinary synthesis reveals a fundamental contradiction: the inherent capacity of living ASCs to sense and respond to local microenvironments directly conflicts with the pharmacological requirements for standardization and predictability. Five major translational bottlenecks are distilled, namely, the absence of functional potency standards, the rodent‑to‑human translational gap, insufficient therapeutic window studies, low‑level clinical evidence outside oculoplastics, and regulatory ambiguity. A corresponding roadmap is proposed, centered on functional potency evaluation, engineered cell‑free products, and an ophthalmic‑specific long‑term safety framework. This review provides a unified theoretical framework for contextualizing the prospects of ASC‑based therapies and offers strategic guidance to facilitate their clinical translation.