Tissue engineering and future directions in regenerative medicine for knee cartilage repair: a comprehensive review.

This review evaluates the current landscape and future directions of regenerative medicine for knee cartilage repair, with a particular focus on tissue engineering strategies. In this context, scaffold-based approaches have emerged as promising solutions for cartilage regeneration. Synthetic scaffolds, while offering superior mechanical properties, often lack the biological cues necessary for effective tissue integration.

Mesenchymal Stem Cell Mechanisms of Action and Clinical Effects in Osteoarthritis: A Narrative Review.

With the insufficient satisfaction rates and high cost of operative treatment for osteoarthritis (OA), alternatives have been sought. Furthermore, the inability of current medications to arrest disease progression has led to rapidly growing clinical research relating to mesenchymal stem cells (MSCs). The availability and function of MSCs vary according to tissue source.

CD146 Pericytes Subset Isolated from Human Micro-Fragmented Fat Tissue Display a Strong Interaction with Endothelial Cells: A Potential Cell Target for Therapeutic Angiogenesis.

Pericytes (PCs) are mesenchymal stromal cells (MSCs) that function as support cells and play a role in tissue regeneration and, in particular, vascular homeostasis. PCs promote endothelial cells (ECs) survival which is critical for vessel stabilization, maturation, and remodeling. In this study, PCs were isolated from human micro-fragmented adipose tissue (MFAT) obtained from fat lipoaspirate and were characterized as NG2/PDGFRβ/CD105 cells.

Characterization of Microfragmented Adipose Tissue Architecture, Mesenchymal Stromal Cell Content and Release of Paracrine Mediators.

The use of microfragmented adipose tissue (µFAT) for the treatment of musculoskeletal disorders, especially osteoarthritis (OA), is gaining popularity, following positive results reported in recent case series and clinical trials. Although these outcomes were postulated to rely on paracrine signals, to date, a thorough fingerprint of released molecules is largely missing. The purpose of this study was to first characterize both structure and cell content of unprocessed lipoaspirate (LA) and µFAT, and further identify and frame the array of signaling factors in the context of OA disease, by means of high throughput qRT-PCR for extracellular-vesicle (EV) embedded miRNAs and proteomics for tissue and secreted factors.

Lipoaspirate Shows In Vitro Potential for Wound Healing.

Mesenchymal stem cells (MSCs) are a promising therapy in wound healing, although extensive time and manipulation are necessary for their use. In our previous study on cartilage regeneration, we demonstrated that lipoaspirate acts as a natural scaffold for MSCs and gives rise to their spontaneous outgrowth, together with a paracrine effect on resident cells that overcome the limitations connected to MSC use. In this study, we aimed to investigate in vitro whether the microfragmented adipose tissue (lipoaspirate), obtained with Lipogems technology, could promote and accelerate wound healing.

Single-Shot Local Injection of Microfragmented Fat Tissue Loaded with Paclitaxel Induces Potent Growth Inhibition of Hepatocellular Carcinoma in Nude Mice.

Hepatocellular carcinoma (HCC) is poorly beneficiated by intravenous chemotherapy due to inadequate availability of drugs at the tumor site. We previously demonstrated that human micro-fragmented adipose tissue (MFAT) and its devitalized counterpart (DMFAT) could be effective natural scaffolds to deliver Paclitaxel (PTX) to tumors in both in vitro and in vivo tests, affecting cancer growth relapse. Here we tested the efficacy of DMFAT-PTX in a well-established HCC in nude mice.

Temporomandibular Joint Arthrocentesis and Microfragmented Adipose Tissue Injection for the Treatment of Internal Derangement and Osteoarthritis: A Randomized Clinical Trial.

Purpose: Internal derangement and osteoarthritis are the most common degenerative temporomandibular joint diseases and initial treatment for such conditions relies on arthrocentesis. Microfragmentation of adipose tissue has been proven in orthopedic literature to represent a more effective method to preserve stem cells, but no application has ever been reported in the temporomandibular joint. The purpose of this randomized clinical trial is to compare standard treatment conducted by injecting hyaluronic acid after the procedure to the new treatment relying upon microfragmented adipose tissue injection using the Lipogems technology.

Case Report: Microfragmented Adipose Tissue Drug Delivery in Canine Mesothelioma: A Case Report on Safety, Feasibility, and Clinical Findings.

Mesothelioma is a rare lethal tumor of dogs and humans involving cavities of the body. Dogs are considered a model for new drugs and therapeutic methods since they present spontaneous diseases similar to humans. Microfragmented adipose tissue (MFAT) uploaded by paclitaxel (PTX) is a drug delivery medium providing slow release of chemotherapic drugs.

Endoscopic repair of a vesicouterine fistula with the injection of microfragmented autologous adipose tissue (Lipogems).

Vesicouterine fistula (VUF) is a rare extra-anatomical communication developing between the uterus or cervix and the urinary bladder, most commonly after an iatrogenic injury during a cesarean section. Patients with VUF may have various clinical presentations, ranging from Youssef's syndrome (vaginal urine leakage, amenorrhea, and menouria) to urinary tract infection and infertility. Quality of life for patients having this pathology is strongly affected owing to the psychological burden.

A new treatment of genito-urinary post-menopausal atrophy with autologous micro-fragmented fat tissue: a thirty-six months follow up case series.

Objective: Genitourinary atrophy is a menopausal pathological change determined by the definitive drop of ovarian hormones' production that can impact heavily on the health status of women, with important direct and indirect social costs. Unfortunately, available treatments are only symptomatic, and they are not able to reverse the atrophy and other related symptoms. Regenerative medicine, with single local injection of autologous micro-fractured fat tissue, could represent a viable new solution for these patients as it not only helps to relieve symptoms, but it also counteracts the mechanisms that lead to the menopausal genitourinary atrophy.

Animal-Based Measures for the On-Farm Welfare Assessment of Geese.

Currently, no specific animal-based measures (ABMs) protocols are available for geese in commercial meat production systems. Following a critical review of the literature and consultation of experts, seven ABMs, potentially valid and feasible for the on-farm welfare assessment of geese, were identified and then tested in 12 farms in Poland to assess their inter-observer reliability. Two observers conducted the assessment, which was divided into two phases.

Is the Piglet Grimace Scale (PGS) a Useful Welfare Indicator to Assess Pain after Cryptorchidectomy in Growing Pigs?

Pig cryptorchidism is a congenital anomaly, which requires surgical intervention. Pain assessment in pig farming has some limitations and consumers are increasingly concerned about suffering linked to on-farm procedures. The PGS seems to be a promising tool for pain assessment in piglets, although it has not been investigated whether this tool is applicable to growing pigs.

Human Adipose Tissue Micro-fragmentation for Cell Phenotyping and Secretome Characterization.

In the past decade, adipose tissue transplants have been widely used in plastic surgery and orthopaedics to enhance tissue repletion and/or regeneration. Accordingly, techniques for harvesting and processing human adipose tissue have evolved in order to quickly and efficiently obtain large amounts of tissue. Among these, the closed system technology represents an innovative and easy-to-use system to harvest, process, and re-inject refined fat tissue in a short time and in the same intervention (intra-operatively).

Evolution of Full Facial Feminization Surgery: Creating the Gendered Face With an All-in-one Procedure.

Facial feminization surgery (FFS) has recently gained popularity to enhance the female facial profile and promote a real transformation of the male to female face in transgender patients. The term involves overlapping of the surgical procedures devoted to feminization and represents a dual and reversible procedure unique in plastic and reconstructive surgery. Indeed, FFS envisages modifications of the hard and soft tissues and is both reductive and augmentative.

Beneficial role of adipose-derived mesenchymal stem cells from microfragmented fat in a murine model of duchenne muscular dystrophy.

Introduction: No etiologic therapy is available for Duchenne muscular dystrophy (DMD), but mesenchymal stem cells were shown to be effective in preclinical models of DMD. The objective of this study is to investigate the effect of microfragmented fat extracted on a murine model of DMD.

Methods: Fat tissue was extracted from healthy human participants and injected IM into DMD mice.

Long-Lasting Anti-Inflammatory Activity of Human Microfragmented Adipose Tissue.

Over the last few years, human microfragmented adipose tissue (MFAT), containing significant levels of mesenchymal stromal cells (MSCs) and obtained from fat lipoaspirate (LP) through a minimal manipulation in a closed system device, has been successfully used in aesthetic medicine as well as in orthopedic and general surgery. Interestingly, in orthopedic diseases, this ready-to-use adipose tissue cell derivative seems to have a prolonged time efficacy even upon a single shot injection into osteoarthritic tissues. Here, we investigated the long-term survival and content of MSCs as well the anti-inflammatory activity of LP and its derived MFAT in vitro, with the aim to better understand a possible in vivo mechanism of action.

Microfragmented human fat tissue is a natural scaffold for drug delivery: Potential application in cancer chemotherapy.

Localization of chemotherapy at the tumor site can improve therapeutic efficacy and reduce systemic toxicity. In previous studies we have shown that mesenchymal stromal cells (MSCs) isolated from bone marrow or adipose tissue can be loaded with the anti-cancer drug Paclitaxel (PTX) and kill cancer cells when localized nearby. We here investigated the capacity of human micro-fragmented adipose tissue (MFAT), used as a natural scaffold of MSCs, to deliver PTX with the idea to improve local drug concentration and to prolong the therapeutic activity.

Differences in prevalence of welfare indicators in male and female turkey flocks (Meleagris gallopavo).

Previous research has shown that the transect walks (TW) method provide a practical and effective approach to welfare assessment in broiler and turkey farms. This method for turkey welfare assessment is reasonable in terms of time demands within minimal costs. Furthermore, TW approach resembles the routine checks used by farmers.

Micro-fragmented fat injection reduces sepsis-induced acute inflammatory response in a mouse model.

Background: Severe sepsis has a high mortality rate. There is increasing evidence that human mesenchymal stem cells possess immunomodulatory properties in sepsis, particularly those from adipose tissue. We hypothesised that micro-fragmented human fat, obtained with minimal alteration of the stromal vascular niche, attenuates the inflammatory response and improves outcome in a murine model of sepsis.

Higher Pericyte Content and Secretory Activity of Microfragmented Human Adipose Tissue Compared to Enzymatically Derived Stromal Vascular Fraction.

Autologous adipose tissue is used for tissue repletion and/or regeneration as an intact lipoaspirate or as enzymatically derived stromal vascular fraction (SVF), which may be first cultured into mesenchymal stem cells (MSCs). Alternatively, transplant of autologous adipose tissue mechanically fragmented into submillimeter clusters has recently showed remarkable efficacy in diverse therapeutic indications. To document the biologic basis of the regenerative potential of microfragmented adipose tissue, we first analyzed the distribution of perivascular presumptive MSCs in adipose tissue processed with the Lipogems technology, observing a significant enrichment in pericytes, at the expense of adventitial cells, as compared to isogenic enzymatically processed lipoaspirates.

A Nonenzymatic and Automated Closed-Cycle Process for the Isolation of Mesenchymal Stromal Cells in Drug Delivery Applications.

The adipose tissue is a good source of mesenchymal stromal cells that requires minimally invasive isolation procedures. To ensure reproducibility, efficacy, and safety for clinical uses, these procedures have to be in compliant with good manufacturing practices. Techniques for harvesting and processing human adipose tissue have rapidly evolved in the last years, and Lipogems® represents an innovative approach to obtain microfragmented adipose tissue in a short time, without expansion and/or enzymatic treatment.

Menopause: new frontiers in the treatment of urogenital atrophy.

Objective: Urogenital atrophy is a degenerative process that may occur during menopause causing debilitating disorders and painful symptomatology. Estrogen therapy slows the onset of atrophy, but it requires ongoing therapy to maintain its effectiveness. To mitigate the degenerative evolutions associated with menopause, patients may benefit from new therapeutic approaches, such as the use of mesenchymal stem cells.

Adipose Tissue and Mesenchymal Stem Cells: State of the Art and Lipogems® Technology Development.

In the past few years, interest in adipose tissue as an ideal source of mesenchymal stem cells (MSCs) has increased. These cells are multipotent and may differentiate in vitro into several cellular lineages, such as adipocytes, chondrocytes, osteoblasts, and myoblasts. In addition, they secrete many bioactive molecules and thus are considered "mini-drugstores.

Angiogenic and anti-inflammatory properties of micro-fragmented fat tissue and its derived mesenchymal stromal cells.

Background: Adipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for advanced cell-based therapies. They are routinely obtained enzymatically from fat lipoaspirate (LP) as SVF, and may undergo prolonged ex vivo expansion, with significant senescence and decline in multipotency. Besides, these techniques have complex regulatory issues, thus incurring in the compelling requirements of GMP guidelines.

Mesenchymal Stem Cells in Lipogems, a Reverse Story: from Clinical Practice to Basic Science.

The idea that basic science should be the starting point for modern clinical approaches has been consolidated over the years, and emerged as the cornerstone of Molecular Medicine. Nevertheless, there is increasing concern over the low efficiency and inherent costs related to the translation of achievements from the bench to the bedside. These burdens are also perceived with respect to the effectiveness of translating basic discoveries in stem cell biology to the newly developing field of advanced cell therapy or Regenerative Medicine.