The effect of exogenous mitochondria in enhancing the survival and volume retention of transplanted fat tissue in a nude mice model

Abstract

Background: Despite the pivotal role of fat grafting in plastic, reconstructive, and aesthetic surgery, inconsistent survival rates of transplanted adipose tissue, primarily due to early ischemic and hypoxic insults, remain a significant challenge. The infusion of healthy mitochondria has emerged as a promising intervention to support tissue recovery from ischemic, hypoxic, and other types of damages across various organ systems. Objectives: This study aims to evaluate the impact of supplementing human adipose tissue grafts with healthy exogenous mitochondria on their volume and mass retention rates when transplanted into the subcutaneous layers of nude mice. This approach seeks to improve and optimize fat grafting techniques. Methods: Human adipose tissues were preconditioned with exogenous mitochondria (10 µg/mL), a combination of exogenous mitochondria and the inhibitor Dyngo-4a, Dyngo-4a alone, or PBS, and then transplanted into the subcutaneous tissue of 24 nude mice. Samples were harvested at 1 and 3 months post-transplantation for analysis of mass and volume retention. The structural morphology and integrity of the adipose tissues were assessed using Hematoxylin and Eosin (H&E) staining. Results: Mitochondrial preconditioning significantly enhanced the retention of mass and volume in fat grafts, demonstrating superior structural morphology and integrity compared to the control group. Conclusions: This study highlights the potential of exogenous mitochondrial augmentation in fat transplantation to significantly improve fat graft survival, thereby optimizing the success of fat grafting procedures.

1. Introduction

Autologous fat grafting has become an essential technique in plastic and reconstructive surgery, offering numerous advantages such as excellent tissue compatibility, the potential for long-term results, simplicity of procedure, low cost, minimal invasiveness, and a low rate of complications. Additionally, the harvesting of subcutaneous adipose tissue for repair and reconstruction can simultaneously improve body contour [1–3]. Initially, autologous fat grafting was primarily utilized to fill soft tissue deficits [4]. However, its applications have expanded to include breast augmentation, facial rejuvenation, scar treatment, wound healing enhancement, and body contouring [5–9].

Despite its wide adoption, the process of fat graft absorption remains inevitable, with retention rates varying significantly from 25-70% [10]. This unpredictable volume retention rate has limited its broader application. The low oxygen and nutrient environment during ex vivo purification and the early ischemic and hypoxic conditions post-transplantation contribute to significant adipocyte death and fat tissue necrosis. Studies have shown that mature adipocytes are particularly sensitive to ischemic and hypoxic damage, with cell death occurring as early as the first day of ischemia [11]. Therefore, improving the survival rate of mature adipocytes post-transplantation is crucial for enhancing the efficacy of this technique.

As the most complex and crucial organelles in eukaryotic cells, mitochondria provide the essential energy required for cellular activities [12]. The essence of ischemic, hypoxic injury, and energy depletion in organ tissues is fundamentally due to mitochondrial dysfunction, leading to cellular energy deficit [13]. Therefore, a sufficient number of high-quality, healthy mitochondria are necessary to maintain tissue homeostasis and cell survival. Recent studies have confirmed the role of intercellular mitochondrial transfer in sustaining homeostasis and cell function. The phenomenon of organelle transfer between mammalian cells through tunneling nanotubes (TNTs) was first documented in 2004 [14]. Following this, the process of mitochondrial transfer from mesenchymal stem cells (MSCs) to mammalian cells was elucidated in 2006 [15]. The transfer of healthy mitochondria has shown significant potential in rescuing tissues from ischemic and hypoxic injuries across various organ systems.