# Toward Personalized ACS Therapy: How Disease Status and Patient Lifestyle Shape the Molecular Signature of Autologous Conditioned Serum

## TL;DR

This study shows that the molecular makeup of autologous conditioned serum varies between osteoarthritis patients and healthy individuals, suggesting the need for personalized treatment approaches.

## Contribution

The study identifies disease-specific and lifestyle-related molecular differences in autologous conditioned serum, supporting the case for stratified therapy.

## Key findings

- OA-derived ACS showed higher levels of MMP-2 and MMP-3 compared to healthy controls.
- TGF-β1 and TGF-β3 were lower in OA-derived ACS, while TGF-β2 showed no significant difference.
- ACS from OA patients had minimal pro-inflammatory mediators and a consistent presence of IL-1RA.

## Abstract

Background/Objectives: Autologous conditioned serum (ACS) is an intra-articular orthobiologic for osteoarthritis (OA) intended to shift the joint cytokine milieu toward an anti-inflammatory, pro-regenerative profile. In the present study, we compared the molecular composition of ACS (specifically IMPACT® ACS) from OA patients with that of healthy controls and assessed demographic and lifestyle influences on mediator levels. Methods: ACS was prepared from the whole blood of 50 OA patients and 20 healthy controls using the IMPACT® centrifugation system (Plasmaconcept, Cologne, Germany) with glass-bead incubation and standardized handling. Cytokines, growth factors, and matrix metalloproteinases (MMPs) were quantified using multiplex immunoassays and ELISA. To account for demographic imbalances across cohorts, the primary findings were verified using age- and sex-adjusted multiple linear regression models. Results: Pro-inflammatory mediators were minimal in both cohorts, with IL-1β undetectable and IL-6 and TNF-α at very low levels. IL-1 receptor antagonist (IL-1RA) was consistently present. Notably, OA-derived ACS exhibited a catabolic shift compared to controls, characterized by significantly higher MMP-2 and MMP-3 levels. Growth factor profiling showed lower TGF-β1 and TGF-β3 in OA-derived ACS, with TGF-β2 showing no significant difference after adjustment. Exploratory stratified analyses indicated potential differences across sex, BMI, smoking status, and diet for select mediators, though subgroup sizes were limited. Conclusions: ACS prepared with a standardized IMPACT® protocol displays a broad anti-inflammatory profile. However, increased MMPs and isoform-specific differences in TGF-β reflect a disease-associated molecular imprint. Consequently, patient-related heterogeneity supports the need for standardized reporting and motivates further research into stratified ACS therapy.