A Phase I Open-Label Study Evaluating the Safety of Acellular Adipose Tissue (AAT), a Novel Soft Tissue Reconstruction Solution, in Healthy Volunteers
Rachael M. Payne, BS, Amy Anderson, BS, Alexis Parrillo, BS, Kaitlyn Sadtler, PhD, Iwen Wu, PhD, Jeffrey Aston, BS, Allison Steiner, PA-C, Carisa M. Cooney, MPH, Damon S. Cooney, MD, PhD, Patrick Byrne, MD, Drew Pardoll, MD, PhD, Jennifer Elisseeff, PhD.
Johns Hopkins University, Baltimore, MD, USA.
PURPOSE: Adipose tissue is used by surgeons for a variety of applications, including soft tissue reconstruction and wound healing. However, harvesting adipose tissue from patients presents challenges such as donor-site morbidity, outcome variability, and difficulty in obtaining adequate volumes to correct large defects. To address this clinical challenge, we aimed to create an "off-the-shelf" adipose material using mechanical and chemical processing techniques which remove lipids and living cells while processing the tissue into an injectable form preferred by patients and physicians. Preclinical testing of this Acellular Adipose Tissue (AAT) conducted in mouse, rat, and swine models demonstrated the biocompatibility of the AAT implants and their ability to provide soft tissue volume replacement while promoting the migration of adipose stem cells (ASCs) into the tissue matrix. The aim of our present study is to assess the safety of AAT in healthy human volunteers.
METHODS: A 12-week, prospective, Phase I study in healthy volunteers assessing the safety and tolerability of AAT intended for the repair of soft tissue defects in humans was initiated. The trial evaluated subcutaneous injections of AAT administered in redundant tissues previously scheduled for surgical removal in an elective surgical procedure (i.e., panniculectomy). Participants enrolled in excision time points ranging from 1 to 12 weeks post-injection. Excised implants were assessed using histopathological analyses including hematoxylin and eosin staining (H&E) and by flow cytometry (FACS). The primary outcome of safety was determined by the incidence and rate of adverse and unanticipated events. The secondary outcome of tolerability was determined by patient- and physician-reported satisfaction with the intervention. Histological analysis evaluated cell migration into the matrix and tissue development, two key components of long-term efficacy.
RESULTS: Eight healthy volunteers participated in this Phase I study assessing the safety of AAT. No patients experienced an adverse or unanticipated event related to their participation in this study. AAT implants were well-tolerated and demonstrated satisfactory participant comfort and physician ease-of-use ratings. Additionally, we evaluated immune profiles of AAT using flow cytometry to quantify the presence of T cells, B cells, dendritic cells, macrophages, M1-polarized (inflammatory) macrophages, and M2-polarized (wound-healing) macrophages. Our preliminary results indicate that AAT is associated with pro-regenerative immune responses, including M2 macrophage polarization and increased IL-4 expression.
CONCLUSION: AAT is a new soft tissue reconstruction material showing promising results in this Phase I study for safe use in humans. Further studies, including a Phase II trial, are necessary to determine efficacy in humans.
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