Adult Human Adipose Tissue Research Articles

Wnt signaling preserves progenitor cell multipotency during adipose tissue development

Mesenchymal stem/progenitor cells are essential for tissue development and repair throughout life, but how they are maintained under chronic differentiation pressure is not known. Using single-cell transcriptomics of human progenitor cells we find that adipose differentiation stimuli elicit two cellular trajectories: one toward mature adipocytes and another toward a pool of non-differentiated cells that maintain progenitor characteristics. These cells are induced by transient Wnt pathway activation and express numerous extracellular matrix genes and are therefore named structural Wnt-regulated adipose tissue cells. We find that the genetic signature of structural Wnt-regulated adipose tissue cells is present in adult human adipose tissue and adipose tissue developed from human progenitor cells in mice. Our results suggest a mechanism whereby adipose differentiation occurs concurrently with the maintenance of a mesenchymal progenitor cell pool, ensuring tissue development, repair and appropriate metabolic control over the lifetime.

Brown adipose tissue human biomarkers: Which one fits best? A narrative review

Adipose tissue (AT) is an endocrine metabolically dynamic active tissue that plays a central role in the systemic energy balance and metabolic regulation. Brown AT represents approximately 1% of adult human AT, with an energy-burning function that uses fat to create heat. Brown AT activity was measured using 18F-fluorodeoxyglucose positron emission tomography/computed tomography. It has been shown that cold exposure could promote brown AT activation. However, many factors, such as aging and body mass index, may interfere with this activity. Many authors have discussed the role of factors specifically secreted by the AT in response to cold exposure. The aim of this review is to properly understand the effects of cold on AT and biomarkers and their possible application in rehabilitation medicine. A comprehensive literature review was performed to identify published studies regarding biomarkers of cold effects on Brown AT searching the following databases: PubMed, Science Direct, and Web of Science, from 2012 to 2022. After evaluation of the inclusion and exclusion criteria, 9 studies were included in this review. We reported the overall influence of cold exposure on brown AT activity, its related biomarkers, and metabolism, demonstrating that the therapeutic role of cold exposure needs to be better standardized. From our data, it is important to design proper clinical trials because most cold applied protocols lack a common and homogeneous methodology.

Human white adipose tissue: A highly dynamic metabolic organ.

Recent technological developments have allowed determination of the age of fat cells and their lipids in adult humans. In contrast to prior views, this has demonstrated a high turnover rate of the fat cells (10%/year) and their unilocular lipid droplets (six times/10 years). Fat cell turnover is increased in obesity and when adipose tissue is composed of many but small adipocytes (hyperplasia, a benign adipose phenotype). While fat mass gain increases adipocyte number and size, only the latter is altered (decreased) after weight loss, which may facilitate weight regain. Fat cell lipid turnover is attenuated in subjects with excess body fat. In the subcutaneous region, this dysregulation occurs already in the overweight state while in the visceral depot, it is only observed in severe obesity. This may explain why the latter depot is particularly pernicious in the overweight/obese state as it allows for more rapid lipid fluxes between visceral fat and the liver. Adipose lipid turnover decreases during ageing due to impaired breakdown (lipolysis) of stored triglycerides. If this decline is not compensated by reduced adipocyte lipid uptake, bodyweight will increase over time. In concordance with this, low lipolysis rates are a risk factor for future weight gain and glucose intolerance. Adipose lipid turnover is also decreased in insulin resistance and certain forms of dyslipidemia. Altogether, adult human adipose tissue is in a highly dynamic state. Alterations in the turnover of fat cells and their lipids are therefore novel factors to consider in the pathophysiology of common metabolic disorders.

Transcriptional Profile of Cytokines, Regulatory Mediators and TLR in Mesenchymal Stromal Cells after Inflammatory Signaling and Cell-Passaging.

Adult human subcutaneous adipose tissue (AT) harbors a rich population of mesenchymal stromal cells (MSCs) that are of interest for tissue repair. For this purpose, it is of utmost importance to determine the response of AT-MSCs to proliferative and inflammatory signals within the damaged tissue. We have characterized the transcriptional profile of cytokines, regulatory mediators and Toll-like receptors (TLR) relevant to the response of MSCs. AT-MSCs constitutively present a distinct profile for each gene and differentially responded to inflammation and cell-passaging. Inflammation leads to an upregulation of IL-6, IL-8, IL-1β, TNFα and CCL5 cytokine expression. Inflammation and cell-passaging increased the expression of HGF, IDO1, PTGS1, PTGS2 and TGFβ. The expression of the TLR pattern was differentially modulated with TLR 1, 2, 3, 4, 9 and 10 being increased, whereas TLR 5 and 6 downregulated. Functional enrichment analysis demonstrated a complex interplay between cytokines, TLR and regulatory mediators central for tissue repair. This profiling highlights that following a combination of inflammatory and proliferative signals, the sensitivity and responsive capacity of AT-MSCs may be significantly modified. Understanding these transcriptional changes may help the development of novel therapeutic approaches.

Exploring the potential of human adipocytes in periodontal regeneration: A review

Stem cells, initially identified in embryonic tissues and later in numerous adult tissues, tend to possess the potentiality to differentiate into various cell types. Though most flexible of all stem cell lines, ethical issues restrict the use of embryonic cells. Furthermore, induced pluripotent stem cells (iPS) and adult stem cells (e.g: bone marrow stroma) can also be used. However, procurement of autologous bone marrow has its potential limitations. An alternate source of autologous adult stem cells which can be procured in large quantities, under local anesthesia, with minimal discomfort would be of keen interest. In the present context, human adult adipose tissue may be the best appropriate alternative source of mesenchymal stem cells. Studies have shown that adipose stem cells (ASCs) extracted from subcutaneous human adult adipose tissue tend to contain heterogeneous cell population called stromal vascular fraction (SVF). It may be used directly or cultured in for selection and expansion of an adherent population, and hence, they are called ASCs. The adipose tissue, obtained by suction-assisted lipectomy (i.e., liposuction), are processed to obtain a fibroblast-like population of cells, also called processed lipoaspirate (PLA). PLA cells has the potentiality to differentiate in vitro into adipogenic, chondrogenic, myogenic, and osteogenic cells in the presence of lineage-specific induction factors. This attributable feature of ASCs may be of significant importance in future clinical cell-based therapy for periodontal disease as well. This review describes current knowledge & recent advances in ASCs & their application. This review describes current knowledge and recent advances in ASCs and their application in periodontal regeneration.

Molecular Mechanisms of P311 on White Adipogenesis

BackgroundThe obesity epidemic is a constant and chronic detriment to US as well as global health outcomes. Two‐thirds of the US population is either overweight or obese, and obesity can be linked to many chronic diseases, including diabetes mellitus, cardiovascular diseases, stroke and cancer. Diet and exercise remains the primary therapeutic approaches, but still obesity (40% of US adult population) incidence and prevalence continues to rise, prompting the development of new interventions. P311 is an 8 kDa protein shown to induce adipogenesis in an in vitro 3T3‐L1 cell culture model (Nunez et al. 2019). In the current study, we investigated the molecular mechanisms of P311 in white adipocyte biology.MethodsBoth male and female C57BL/6 control mice and P311 knockout (KO) mice were used for this study. Adipocytes were isolated from individual white adipose tissue depots and adipocyte number and size were quantified using LipidTox staining followed by Guava EasyCyte analysis. Additionally adipocyte cellular functions of P311 like apoptosis, lipophagy and adipose tissue macrophage numbers were verified in P311 KOs and compared with wild type control mice. Real‐time PCR, western blot and immunohistology studies were conducted as described by Badri et al. (2013) and Nunez et al. (2019)ResultsP311 was expressed in murine gonadal and subcutaneous white adipose tissue. White adipocytes isolated from 4‐month‐old mice had significantly higher levels of P311 compared to adipocytes isolated from the white subcutaneous adipose tissue of 1‐month‐old mice. However, progenitor cells (stromal vascular fraction) showed no (basal) expression of P311. P311 KO mice showed decreased PPARγ2 expression. P311 KO mice did not differ from wild type mice in subcutaneous or gonadal white adipose tissue weights, but they had fewer and enlarged adipocytes. Further, P311 KOs also showed decreased apoptosis and lipophagy along with decreased adipocyte macrophage numbers and browning of white adipose tissue. In addition, adult human visceral adipose tissue also showed the expression of P311 in adipocytes implicating a translational role for P311 in adipogenesis and obesity.ConclusionsP311 plays a key role in white adipogenesis and browning of WAT partly through modulating PPARγ2 and also by regulating adipocyte cellular processes including adipocyte apoptosis, lipophagy, browning and macrophage numbers.Support or Funding Information• 2019 Medical Student Summer Research and Public Health Experience (Morehouse School of Medicine)• NIMHD/NIH grant funding through S21MD000101 (to Morehouse School of Medicine)• U54MD008621 (Hampton University, Hampton, VA)

Sexual Dimorphisms in Adult Human Brown Adipose Tissue.

This study aimed to quantify and compare the amount, activity, and anatomical distribution of cold-activated brown adipose tissue (BAT) in healthy, young, lean women and men. BAT volume and 18 F-fluorodeoxyglucose uptake were measured by positron emission tomography and computerized tomography in 12 women and 12 men (BMI 18.5-25 kg/m2 , aged 18-35 years) after 5 hours of exposure to their coldest temperature before overt shivering. Women had a lower detectable BAT volume than men (P = 0.03), but there was no difference after normalizing to body size. The mean BAT glucose uptake and relative distribution of BAT did not differ by sex. 18 F-fluorodeoxyglucose uptake consistent with BAT was observed in superficial dorsocervical adipose tissue of 6 of 12 women but only 1 of 12 men (P = 0.02). This potential BAT depot would pose fewer biopsy risks than other depots. Despite differences in adiposity and total BAT volume, we found that healthy, lean, young women and men do not differ in the relative amount, glucose uptake, and distribution of BAT. Dorsocervical 18 F-fluorodeoxyglucose uptake was more prevalent in women and may be a remnant of interscapular BAT seen in human newborns. Future studies are needed to discern how BAT contributes to whole-body thermal physiology and body weight regulation in women and men.

Estimation of non-shivering thermogenesis and cold-induced nutrient oxidation rates: Impact of method for data selection and analysis

Since the discovery of active brown adipose tissue in human adults, non-shivering cold-induced thermogenesis (CIT) has been regarded as a promising tool to combat obesity. However, there is a lack of consensus regarding the method of choice to analyze indirect calorimetry data from a CIT study. We analyzed the impact of methods for data selection and methods for data analysis on measures of cold-induced energy expenditure (EE) and nutrient oxidation rates. Forty-four young healthy adults (22.1±2.1 years old, 25.6±5.2kg/m2, 29 women) participated in the study. Resting metabolic rate (RMR), cold-induced thermogenesis (CIT), and cold-induced nutrient oxidation rates were estimated by indirect calorimetry under fasting conditions during 1h of cold exposure combining air conditioning (19.5-20°C) and a water perfused cooling vest set at a temperature of 4°C above the individual shivering threshold. We applied three methods for data selection: (i) time intervals every 5min (5min-TI), (ii) the most stable 5-min period of every forth part of the cold exposure (5min-SS-4P), and (iii) the most stable 5-min period of every half part of the cold exposure (5min-SS-2P). Lately we applied two methods for data analysis: (i) area under the curve as a percentage of the baseline RMR (AUC) and; (ii) the difference between EE at the end of the cold exposure and baseline RMR (Last-RMR). Mean overall CIT estimation ranged from 11.6±10.0 to 20.1±17.2 %RMR depending on the methods for data selection and analysis used. Regarding methods for data selection, 5min-SS-2P did not allow to observe physiologically relevant phenomena (e.g. metabolic shift in fuel oxidation; P=0.547) due to a lack of resolution. The 5min-TI and 5min-SS-4P methods for data selection seemed to be accurate enough to observe physiologically relevant phenomena (all P<0.014), but not comparable for estimating over-all CIT and cold-induced nutrient oxidation rates (P<0.01). Regarding methods for data analysis, the AUC seemed to be less affected for data artefacts and to be more representative in participants with a non-stable energy expenditure during cold exposure. The methods for data selection and analysis can have a profound impact on CIT and cold-induced nutrient oxidation rates estimations, and therefore, it is mandatory to unify it across scientific community to allow inter-study comparisons. Based on our findings, 5min-TI should be considered the method of choice to study dynamics (i.e. changes across time) of CIT and cold-induced nutrient oxidation rates, while 5min-SS-4P and AUC should be the method of choice when computing CIT and cold-induced nutrient oxidation rates as a single value.

Fractionated human adipose tissue as a native biomaterial for the generation of a bone organ by endochondral ossification

Many steps are required to generate bone through endochondral ossification with adipose mesenchymal stromal cells (ASC), from cell isolation to in vitro monolayer expansion, seeding into scaffolds, cartilaginous differentiation and in vivo remodeling. Moreover, monolayer expansion and passaging of ASC strongly decreases their differentiation potential. Here, we propose that adipose tissue itself can be used as scaffold for ASC expansion and endochondral ossification. Human liposuctions were fractionated and cultured for 3 weeks with proliferative medium in suspension. The resulting constructs, named Adiscaf, were compared to constructs generated with a previously developed, control approach, i.e. collagen sponges seeded with monolayer-expanded ASC. After 4 weeks of chondrogenic differentiation, Adiscaf contained cartilage tissue, characterized by glycosaminoglycans and collagen type II. After 2 additional weeks of hypertrophic differentiation, Adiscaf showed upregulation of hypertrophic markers at the gene expression and protein levels. After 8 weeks of in vivo implantation, Adiscaf resulted in ectopic bone tissue formation, including bone marrow elements. Adiscaf showed superior in vitro differentiation and in vivo performance as compared to the control paradigm involving isolation and monolayer expansion of ASC. This new paradigm exploits the physiological niche of adipose tissue and strongly suggests a higher functionality of cells inside adipose tissue after in vitro expansion. This study demonstrates that adult human adipose tissue used as a native construct can generate a bone organ by endochondral ossification. The concept could be exploited for the generation of osteogenic grafts for bone repair. Statement of SignificanceIn this study we used adult human adipose tissue as scaffolding materials (called Adiscaf) to generate a bone organ by endochondral ossification. Adiscaf concept is based on the culture of adipose tissue cells inside their native microenvironment for the generation of osteogenic grafts for bone repair. This simplified approach overcomes several limitations linked to the current techniques in bone tissue engineering, such as isolation of cells and inadequate properties of the biomaterials used as scaffolds. In addition, the present paradigm proposes to exploit physiological niches in order to better maintain the functionality of cells during their in vitro expansion. This project not only has a scientific impact by evaluating the impact of native physiological niches on the functionality and chondrogenic differentiation of mesenchymal progenitors but also a clinical impact to generate osteogenic grafts and/or osteoinductive materials for bone regeneration and repair.

An exploratory study on the preparation and evaluation of a “same-day” adipose stem cell–based tissue-engineered vascular graft

ObjectiveTissue-engineered vascular grafts containing adipose-derived mesenchymal stem cells offer an alternative to small-diameter vascular grafts currently used in cardiac and lower-extremity revascularization procedures. Adipose-derived, mesenchymal stem cell–infused, tissue-engineered vascular grafts have been shown to promote remodeling and vascular homeostasis in vivo and offer a possible treatment solution for those with cardiovascular disease. Unfortunately, the time needed to cultivate adipose-derived mesenchymal stem cells remains a large hurdle for tissue-engineered vascular grafts as a treatment option. The purpose of this study was to determine if stromal vascular fraction (known to contain progenitor cells) seeded tissue-engineered vascular grafts would remain patent in vivo and remodel, allowing for a “same-day” process for tissue-engineered vascular graft fabrication and implantation. MethodsStromal vascular fraction, obtained from adult human adipose tissue, was seeded within 4 hours after acquisition from the patient onto poly(ester urethane)urea bilayered scaffolds using a customized rotational vacuum seeding device. Constructs were then surgically implanted as abdominal aortic interposition grafts in Lewis rats. ResultsFindings revealed patency in 5 of 7 implanted scaffolds at 8 weeks, along with neotissue formation and remodeling occurring in patent tissue-engineered vascular grafts. Patency was documented using angiography and gross inspection, and remodeling and vascular components were detected using immunofluorescent chemistry. ConclusionsA “same-day” cell-seeded, tissue-engineered vascular graft can remain patent after implantation in vivo, with neotissue formation and remodeling occurring by 8 weeks.

Lessons from Cre-Mice and Indicator Mice.

The adult human adipose tissue is predominantly composed of white adipocytes. However, within certain depots, adipose tissue contains thermogenically active brown-like adipocytes, which have been evolutionarily conserved in mammals. This chapter will give a brief overview on the methods used to genetically target and trace both white and brown adipocytes using techniques such as bacterial artificial chromosome (BAC) cloning to create transgenic mouse models and the tools with which genetic recombination is mediated in vivo (e.g., Cre-loxP, CreERT, and Tet-On). The chapter furthermore critically discusses the strength and limitation of the various systems used to target mature white and brown adipocytes (ap2-Cre, Adipoq-Cre, and Ucp1-Cre). Based on these systems, it is evident that our knowledge of mature adipocyte categorization into brown, white, brite, or beige adipocytes is strongly influenced by the use of the various genetic mouse models described in this chapter. Our evaluation of different studies using the aforementioned systems focuses on key genes, which have been reported to maintain adipocyte's function (insulin receptor, Raptor, or Atgl).

Factors involved in white‐to‐brown adipose tissue conversion and in thermogenesis: a review

Obesity is the result of energy intake chronically exceeding energy expenditure. Classical treatments against obesity do not provide a satisfactory long-term outcome for the majority of patients. After the demonstration of functional brown adipose tissue in human adults, great effort is being devoted to develop therapies based on the adipose tissue itself, through the conversion of fat-accumulating white adipose tissue into energy-dissipating brown adipose tissue. Anti-obesity treatments that exploit endogenous, pharmacological and nutritional factors to drive such conversion are especially in demand. In the present review, we summarize the current knowledge about the various molecules that can be applied in promoting white-to-brown adipose tissue conversion and energy expenditure and the cellular mechanisms involved.

Isolation and Primary Culture of Adult Human Adipose-derived Stromal/Stem Cells.

Adipose-derived stromal/stem cells (ASCs) are multipotent cells that can be isolated from adipose tissue. Studies have shown that cells have the capacity to self-renew and differentiate into adipocyte, chondrocyte, myocyte, and osteoblast lineages. Thus, significant interest regarding their use for regenerative purposes to restore aging or damaged tissue has grown in recent decades. These cells have also been shown to immunomodulate the microenvironment and secrete abundant growth factors, which minimize inflammation and aid repair and regeneration. ASCs can be readily isolated from the stromal vascular fraction (SVF) of lipoaspirates. Given their ease of accessibility, bountiful source, and potential application in regenerative medicine and tissue engineering, there is growing interest in the characterization and utilization of ASCs. This protocol describes the isolation of ASCs from adult human adipose tissue as well as methods for culture maintenance including expansion and cryopreservation.

Brown Adipose Tissue- What is Known and What to Be Known?

1. Abstract Adult human brown adipose tissue has been known for a long time as a vestigial organ with limited or no function that found with opulencein newborn and infants, helping them controlling their body thermogenesis without shivering, followed by its gradual disappearance with age (disparate form animals like rodents which keep BAT in adult life). Recently BAT existence, distribution and activity has been unraveled accidentally. There by researches on BAT demonstrated undeniable links to human metabolism and body composition. The fixed facts regarding body metabolism and energy homeostasis that have been granted for centuries are about to exhibit different perspectives. BAT discovery ignited a new line of research focusing on modulating energy expenditure and hence controlling many metabolic phenomena. Here we offer a brief review of what have been reported regarding BAT and it activity with pointing to novel challenges that need to be unveiled.

Human Adipose Stem Cells: From Bench to Bedside.

Stem cell-based therapies for repair and regeneration of different tissues are becoming more important in the treatment of several diseases. Adult stem cells currently symbolize the most available source of cell progenitors for tissue engineering and repair and can be harvested using minimally invasive procedures. Moreover, mesenchymal stem cells (MSCs), the most widely used stem cells in stem cell-based therapies, are multipotent progenitors, with capability to differentiate into cartilage, bone, connective, muscle, and adipose tissue. So far, bone marrow has been regarded as the main source of MSCs. To date, human adult adipose tissue may be the best suitable alternative source of MSCs. Adipose stem cells (ASCs) can be largely extracted from subcutaneous human adult adipose tissue. A large number of studies show that adipose tissue contains a biologically and clinically interesting heterogeneous cell population called stromal vascular fraction (SVF). The SVF may be employed directly or cultured for selection and expansion of an adherent population, so called adipose-derived stem cells (ASCs). In recent years, literature based on data related to SVF cells and ASCs has augmented considerably: These studies have demonstrated the efficacy and safety of SVF cells and ASCs in vivo in animal models. On the basis of these observations, in several countries, various clinical trials involving SVF cells and ASCs have been permitted. This review aims at summarizing data regarding either ASCs cellular biology or ASCs-based clinical trials and at discussing the possible future clinical translation of ASCs and their potentiality in cell-based tissue engineering.

Neural crest stem cells are also present is adult human bone marrow and adipose tissue

Neural crest stem cells are also present is adult human bone marrow and adipose tissue

The human retinal stem niches could overlap a vascular anatomical pattern.

The human retinal stem niches could overlap a vascular anatomical pattern.

Cold-activated brown adipose tissue in human adults: methodological issues.

The relevance of functional brown adipose tissue (BAT) depots in human adults was undisputedly proven approximately seven years ago. Here we give an overview of all dedicated studies that were published on cold-induced BAT activity in adult humans that appeared since then. Different cooling protocols and imaging techniques to determine BAT activity are reviewed. BAT activation can be achieved by means of air- or water-cooling protocols. The most promising approach is individualized cooling, during which subjects are studied at the lowest temperature for nonshivering condition, probably revealing maximal nonshivering thermogenesis. The highest BAT prevalence (i.e., close to 100%) is observed using the individualized cooling protocol. Currently, the most widely used technique to study the metabolic activity of BAT is deoxy-2-[18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) imaging. Dynamic imaging provides quantitative information about glucose uptake rates, whereas static imaging reflects overall BAT glucose uptake, localization, and distribution. In general, standardized uptake values (SUV) are used to quantify BAT activity. An accurate determination of total BAT volume is hampered by the limited spatial resolution of the PET image, leading to spillover. Different research groups use different SUV threshold values, which make it difficult to directly compare BAT activity levels between studies. Another issue is the comparison of [18F]FDG uptake in BAT with respect to other tissues or upon with baseline values. This comparison can be performed by using the “fixed volume” methodology. Finally, the potential use of other relatively noninvasive methods to quantify BAT, like magnetic resonance imaging or thermography, is discussed.

Direct Differentiation of Homogeneous Human Adipose Stem Cells Into Functional Hepatocytes by Mimicking Liver Embryogenesis

The potential of adult human adipose tissue stem cells (hASCs) to differentiate into hepatocytes has generated much excitement over the possible use of hASCs in therapeutic applications. An understanding of the molecular mechanisms that underlie the plasticity of hASCs toward hepatocytes will help to make this possibility a reality. Herein, we show that a homogenous population of hASCs characterized by a high level of CD73, CD90, and CD105 express the pluripotent transcription factors OCT4, SOX2, NANOG, and SALL4 under proliferation conditions. A high level of activin A allows for hASCs acquiring the fate of definitive endoderm (DE) cells and expressing the specific transcription factors HEX, FOXA2, SOX17, and GATA4 synchronously. Using a reproducible three-stage method by mimicking liver embryogenesis, hASCs were directed to differentiate into functional hepatocytes. In the first stage, hASCs were induced to become DE cells by 2 days cultured in serum-free medium and 3 days of activin A treatment. Next, the presence of fibroblast growth factor (FGF) 4 and bone morphogenetic protein (BMP) 2 in the medium for 5 days induced efficient hepatic differentiation from DE cells. After 10 days of further maturated by the sequential exposure to hepatocyte growth factor (HGF), oncostatin M (OSM), and dexamethasone (DEX), the hASC-derived hepatocytes expressed mature hepatocytes marker and exhibited functional characterization, including albumin secretion, glycogen storage, urea production, activity of drug transporters, and cytochrome P450 activity. These findings will be useful for the implementation of hASC-derived hepatocytes in therapeutic purposes, metabolic analyses, drug toxicity screening, and studies of hepatocyte function.

Human Adipose Tissue Possesses a Unique Population of Pluripotent Stem Cells with Nontumorigenic and Low Telomerase Activities: Potential Implications in Regenerative Medicine

In this study, we demonstrate that a small population of pluripotent stem cells, termed adipose multilineage-differentiating stress-enduring (adipose-Muse) cells, exist in adult human adipose tissue and adipose-derived mesenchymal stem cells (adipose-MSCs). They can be identified as cells positive for both MSC markers (CD105 and CD90) and human pluripotent stem cell marker SSEA-3. They intrinsically retain lineage plasticity and the ability to self-renew. They spontaneously generate cells representative of all three germ layers from a single cell and successfully differentiate into targeted cells by cytokine induction. Cells other than adipose-Muse cells exist in adipose-MSCs, however, do not exhibit these properties and are unable to cross the boundaries from mesodermal to ectodermal or endodermal lineages even under cytokine inductions. Importantly, adipose-Muse cells demonstrate low telomerase activity and transplants do not promote teratogenesis in vivo. When compared with bone marrow (BM)- and dermal-Muse cells, adipose-Muse cells have the tendency to exhibit higher expression in mesodermal lineage markers, while BM- and dermal-Muse cells were generally higher in those of ectodermal and endodermal lineages. Adipose-Muse cells distinguish themselves as both easily obtainable and versatile in their capacity for differentiation, while low telomerase activity and lack of teratoma formation make these cells a practical cell source for potential stem cell therapies. Further, they will promote the effectiveness of currently performed adipose-MSC transplantation, particularly for ectodermal and endodermal tissues where transplanted cells need to differentiate across the lineage from mesodermal to ectodermal or endodermal in order to replenish lost cells for tissue repair.