Raheel Arshad Zubair, MD, Department of Research, Cosmetic Laser Dermatology, 9339 Genesee Avenue, Suite 300, San Diego, CA 92121, United States. raheel.zubair@platinumderm.com
Research Domain of This Article
Cell & Tissue Engineering
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Raheel Arshad Zubair, Xi-Han Zhou, Sabrina Guillen Fabi, Department of Research, Cosmetic Laser Dermatology, San Diego, CA 92121, United States
Sabrina Guillen Fabi, Department of Dermatology, University of California San Diego, La Jolla, CA 92093, United States
Author contributions: Zubair RA and Fabi SG designed and coordinated the study, and interpreted the data; Zubair RA, Zhou XH, and Fabi SG acquired and analyzed the data; Zubair RA wrote the final manuscript draft; all authors approved the final version of the article.
Supported by an unrestricted educational grant from Galderma Laboratories; Fort Worth, TX, United States.
Institutional review board statement: The study was approved by Advarra IRB (protocol number #00082861). This study used archived subcutaneous adipose tissue samples obtained from participants enrolled in a previous randomized controlled trial. No new human interventions were performed. Both studies complied with the Helsinki Declaration.
Conflict-of-interest statement: Fabi SG is an investigator, consultant and speaker for AbbVie, Inc., Galderma Laboratories, and Revance Therapeutics. Zubair RA and Zhou XH report there are no competing interests to declare.
Data sharing statement: The data reported in this paper will be shared by the communicating author upon reasonable request.
Corresponding author: Raheel Arshad Zubair, MD, Department of Research, Cosmetic Laser Dermatology, 9339 Genesee Avenue, Suite 300, San Diego, CA 92121, United States. raheel.zubair@platinumderm.com
Received: November 5, 2025 Revised: December 9, 2025 Accepted: February 11, 2026 Published online: April 26, 2026 Processing time: 166 Days and 12.5 Hours
Abstract
BACKGROUND
Poly-L-lactic acid (PLLA) has been demonstrated to grow both subcutaneous adipose tissue and the dermis which may occur through stimulation of adipose-derived stem cells (ADSC). These cells maintain the integumentary system by regulating fibroblasts and immune cells, sustaining the extracellular matrix, and combating oxidative stress.
AIM
To use multiplex immunofluorescence to characterize macrophage subtypes involved in the PLLA-macrophage-fibroblast encapsulations on previously obtained biopsy tissue and quantify changes in the subcutaneous adipose tissue of hip dells (lateral gluteal cleft) treated with PLLA. The secondary objective was to use immunofluorescence to characterize macrophage polarization in the immune response to PLLA treatment.
METHODS
Multiplex immunofluorescence was used to characterize the macrophage subtypes involved in the PLLA-macrophage-fibroblast encapsulations on previously obtained biopsies from a previous randomized, placebo-controlled clinical trial.
RESULTS
Absolute counts of ADSC and fibroblasts increased markedly in PLLA-treated tissues compared to baseline and controls. PLLA-macrophage-fibroblast encapsulations were high in ADSC with intense CD105, CD90, preadipocyte factor 1, proliferating cell nuclear antigen, β-catenin levels. This contrasts sharply with distant tissue, which was near absent in those signals and instead dominated by perilipin 1 consistent with mature adipocytes. Additionally, M2 macrophages predominated over M1 in these encapsulations, consistent with late-stage wound remodeling rather than infection-associated inflammation.
CONCLUSION
The study represents the first time native ADSC phenotype cells have been expanded in humans in vivo. PLLA has a well-established three-decade safety record as a minimally invasive skin-rejuvenation and volumization agent. This study suggests PLLA promotes a regenerative environment and may expand progenitor populations in vivo.
Core Tip: This study provides the first in vivo evidence that poly-L-lactic acid stimulates proliferation of cells expressing adipose-derived stem cell phenotype in human subcutaneous tissue. Using multiplex immunofluorescence on archived biopsy samples from a previous randomized clinical trial, poly-L-lactic acid-treated sites demonstrated marked expansion of cells exhibiting adipose-derived stem cell phenotype and fibroblasts in addition to a predominance of M2 macrophages consistent with a remodeling response. Most importantly, this may represent a novel regenerative paradigm using a minimally invasive technique.
