Clinical manufacturing of adipose-derived stem cells for therapeutic use: current technologies, quality systems and production challenges.

Abstract

Introduction: This systematic review evaluated manufacturing technologies for adipose-derived stem cells (ADSCs), focusing on automation, quality control, potency, scalability, cost, and regulatory compliance.

Methods: Following PRISMA guidelines, PubMed, Embase, and Web of Science were searched for English-language studies published January 2020-September 2025. Studies addressing clinical-grade ADSC manufacturing, quality control, regulatory compliance, or production economics were included; non-ADSC studies, reviews, case reports, and conference abstracts were excluded. Two reviewers qualitatively assessed methodological quality and bias. Heterogeneity precluded meta-analysis, so findings were synthesized narratively.

Results: Forty-six studies were included; participant numbers were inconsistently reported, as the review focused on manufacturing processes. Automated bioreactors achieved 2- to 10-fold higher yields than flask-based approaches, with improved reproducibility and reduced contamination risk. Five validated platforms were identified. GMP production costs ranged from $15,000 to $50,000 per dose; automation offered potential reductions of 20%-40%. Key limitations included 3- to 5-fold inter-donor variability, 15%-25% batch-to-batch variation, and 5%-10% manufacturing failure rates.

Conclusions: ADSC manufacturing is progressing toward scalable production, but clinical translation remains constrained by biological variability, limited potency-assay validation, high costs, and regulatory complexity. Standardization and clinically relevant potency assays are needed to improve consistency and access.