Adipose-Derived Stem Cells for Facial Rejuvenation

The interest in regenerative medicine is increasing, and it is a dynamically developing branch of aesthetic surgery. Biocompatible and autologous-derived products such as platelet-rich plasma or adult mesenchymal stem cells are often used for aesthetic purposes. Their application originates from wound healing and orthopaedics. Adipose-derived stem cells are a powerful agent in skin rejuvenation. They secrete growth factors and anti-inflammatory cytokines, stimulate tissue regeneration by promoting the secretion of extracellular proteins and secrete antioxidants that neutralize free radicals. In an office procedure, without cell incubation and counting, the obtained product is stromal vascular fraction, which consists of not only stem cells but also other numerous active cells such as pericytes, preadipocytes, immune cells, and extra-cellular matrix. Adipose-derived stem cells, when injected into dermis, improved skin density and overall skin appearance, and increased skin hydration and number of capillary vessels. The main limitation of mesenchymal stem cell transfers is the survival of the graft. The final outcomes are dependent on many factors, including the age of the patient, technique of fat tissue harvesting, technique of lipoaspirate preparation, and technique of fat graft injection. It is very difficult to compare available studies because of the differences and multitude of techniques used. Fat harvesting is associated with potentially life-threatening complications, such as massive bleeding, embolism, or clots. However, most of the side effects are mild and transient: primarily hematomas, oedema, and mild pain. Mesenchymal stem cells that do not proliferate when injected into dermis promote neoangiogenesis, that is why respectful caution should be taken in the case of oncologic patients. A longer clinical observation on a higher number of participants should be performed to develop reliable indications and guidelines for transferring ADSCs.

New strategies in regenerative medicine and surgery and their application to orthopedic surgery field: The bio-active composite therapies (BACTs)

Regenerative Medicine and Surgery is a rapidly expanding branch of translational research in tissue engineering, cellular and molecular biology. To date, the methods to improve cell intake, survival and isolation need to comply with a complex and still unclear regulatory frame, becoming everyday more restrictive and often limiting effectiveness and outcome of the therapeutic choices. Thus, the author developed a novel regenerative strategy, based on the synergic action of several bio-active components, called the Bio-Active Composite Therapies (BACTs) to improve grafted cells intake and survival in total compliance with the legal and ethical limits of the current regulatory frame. The rationale at the origin of this new technology is based on the evidence that cells need supportive substrate to survive in vitro and this observation, applying the concept of translational medicine, is true also in vivo. Many different sources have been used in the past for MSCs, molecules and growth factors (GF) isolation and extraction, but the Adipose Tissue and its Stromal Vascular Fraction (SVF) definitely remains the most valuable, abundant, safe and reliable. Bio-Active Composite Mixtures (BACMs) are tailor-made injectable “cocktails” containing several bio-active components to support cells survival and induce a strong regenerative response in vivo by stimulating the recipient site to act as an in-situ real Bioreactor. In this article, the author analyze the main causes of cell’s death and the strategies for preventing it, and outline all the technical steps for preparing the main components of BACMs and the different mixing modalities to obtain the most efficient regenerative action on different clinical and pathological conditions in several surgical specialties. Orthopedic Surgery is definitely the one that most can benefit of these new therapeutic strategies. The final part of this work is anticipating the logical and sequential evolution toward other fundamental technical steps for further supporting and enhancing the most efficient regenerative activity.

Autologous Fat Grafting – A Step Forward in Wound Management

Autologous fat grafting (AFG) is an emerging therapeutic option for wounds that are not ready for grafting. The regenerative potential of autologous fat lies in the adipose derived stem cells (ADSCs) contained within the stromal vascular fraction (SVF), which are capable of differentiating into multiple cell lineages. However to date, there has been no comprehensive evaluation of its efficacy in acute complicated wounds. This study aims to critically evaluate the efficacy and safety of AFG in cutaneous wound healing. Materials and Methods: This prospective, quasi experimental study was conducted in the Department Of Plastic Surgery, SIMS, Lahore, between June 2020 and June 2021. Thirty patients with pale granulation, not ready for grafting with no vital structure exposed were included in the study after detailed history, examination and were photographed pre and postoperatively. The procedure was performed under local anaesthesia. 40 to 80 ml fat was harvested from lower abdomen and after emulsification, placed over the wound wrapped in sufra tulle dressing. The dressing was changed on third postoperative day and outcome was assessed on clinical grounds. Results: Thirty patients (M:F Ratio 1.75:1) with mean age 30 years (Range 13-45 years) were included in this study with post traumatic (n = 23) and post infective (n = 7). Of 27 patients who completed their follow up, all had healthy granulation tissue which was later on grafted. Mean number of fat dressing sessions were 2 (Range 1-3). Conclusion: Autologous fat grafting has shown promising results for cutaneous wounds without any unacceptably high complication rates reported so far. Randomised controlled trials should be done on a larger scale to prove its efficacy in the management of complicated wounds.

Adipocyte-specific deletion of PIP5K1c reduces diet-induced obesity and insulin resistance by increasing energy expenditure

Background Phosphatidylinositol 4-phosphate 5-kinase type I c (PIP5K1c) catalyses the synthesis of phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphorylating phosphatidylinositol 4 phosphate, which plays multiple roles in regulating focal adhesion formation, invasion, and cell migration signal transduction cascades. Here, a new physiological mechanism of PIP5K1c in adipocytes and systemic metabolism is reported. Methods Adipose-specific conditional knockout mice were generated to delete the PIP5K1c gene in adipocytes. In addition, in vitro research investigated the effect of PIP5K1c deletion on adipogenesis. Results Deletion of PIP5K1c in adipocytes significantly alleviated high fat diet (HFD)-induced obesity, hyperlipidaemia, hepatic steatosis, and insulin resistance. PIP5K1c deficiency in adipocytes also decreased adipocyte volume in HFD-induced obese mice, whereas no significant differences were observed in body weight and adipose tissue weight under normal chow diet conditions. PIP5K1c knockout in adipocytes significantly enhanced energy expenditure, which protected mice from HFD-induced weight gain. In addition, adipogenesis was markedly impaired in mouse stromal vascular fraction (SVF) from PIP5K1c-deleted mice. Conclusion Under HFD conditions, PIP5K1c regulates adipogenesis and adipose tissue homeostasis. Together, these data indicate that PIP5K1c could be a novel potential target for regulating fat accumulation, which could provide novel insight into the treatment of obesity.

Research progress on preparation, mechanism, and clinical application of nanofat

Autologous adipose tissue is an ideal soft tissue filling material in theory, which has the advantages of easy access, comprehensive source, and high biocompatibility and is now widely used in clinical practice. Based on the above benefits of autologous fat, autologous fat grafting is an essential technique in plastic surgery. Conventional macrofat is used to improve structural changes after soft tissue damage or loss caused by various causes such as disease, trauma, or aging. Due to the large diameter of particles and to avoid serious complications such as fat embolism, blunt needles with larger diameters (2mm) are required, making the macrofat grafting difficult to the deep dermis and sub-dermis. Nanofat grafting is a relatively new technology that has gained popularity in cosmetic surgery in recent years. Nanofat is produced by mechanical shuffling and filtration of microfat, which is harvested by liposuction. The harvesting and processing of nanofat are cost-effective as it does not require additional equipment or culture time. Unlike microfat, nanofat particles are too small to provide a notable volumizing effect. Studies have shown that nanofat contains abundant stromal vascular fraction (SVF) cells and adipose-derived stem cells (ADSCs), which help reconstruct dermal support structures, such as collagen, and regenerate healthier, younger-looking skin. Moreover, the fluid consistency of nanofat allows application in tissue regeneration, such as scars, chronic wounds, and facial rejuvenation. This article reviews the current research progress on the preparation, mechanism, and clinical application of nanofat.

Tissue Stromal Vascular Fraction Improves Early Scar Healing: A Prospective Randomized Multicenter Clinical Trial

Background Wound healing and scar formation depends on a plethora of factors. Given the impact of abnormal scar formation, interventions aimed to improve scar formation would be most advantageous. Tissue stromal vascular fraction (tSVF) of adipose tissue is composed of a heterogenous mixture of cells embedded in extracellular matrix. It contains growth factors and cytokines involved in wound healing processes, eg, parenchymal proliferation, inflammation, angiogenesis, and matrix remodeling. Objectives In this study, we hypothesized that tSVF reduces post-surgical scar formation. Methods This prospective, double-blind, placebo-controlled, randomized trial was conducted between 2016 and 2020. Forty mammoplasty patients were enrolled and followed for 1 year. At the end of the mammoplasty procedure, all patients received tSVF in the lateral 5 cm of the horizontal scar of one breast and a placebo injection in the contralateral breast to serve as an intra-patient control. Primary outcome was scar quality using the patient and observer scar assessment scale (POSAS). Secondary outcomes were obtained with photograph evaluation and histological analysis of scar tissue samples. Results Thirty-four of 40 patients completed follow-up. Six months postoperatively, injection of tSVF had significantly improved postoperative scar appearance as assessed by POSAS questionnaire (observer and patient questionnaire). No difference was observed at 12 months postoperatively. No improvement was seen based on the evaluation of photographs and histological analysis of postoperative scars between both groups. Conclusions Injection of tSVF resulted in improved wound healing and reduced scar formation at 6 months postoperative, without any noticeable advantageous effects seen at 12 months.