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Adipose Stem Cells 3.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 27428

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Prof. Dr. Hirofumi Noguchi

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Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Okinawa, Japan
Interests: pancreatic islet transplantation; islet regeneration; stem cell biology
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Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our 2019 Special Issue, “Adipose Stem Cells 2019”.

Adipose tissue is a complex organ and, in this last years, it has received considerable attention due to its high stem cell content of adipose stem cells (ASC).

By definition, a stem cell is characterized by its ability to undergo self-renewal and differentiation, and form terminally differentiated cells. Ideally, a stem cell for regenerative medicinal applications should meet the following set of criteria: (i) found in abundant quantities (millions to billions of cells), (ii) able to be collected and harvested by a minimally invasive procedure, (iii) can be differentiated along multiple cell lineage pathways in a reproducible manner, and (iv) can be safely and effectively transplanted to either an autologous or allogeneic host. Adipose tissue serves as an abundant, accessible, and rich source of adult stem cells with multipotent properties suitable for tissue engineering and regenerative medical applications.

The plasticity of ASC most often refers to the inherent ability of stem cells to cross lineage barriers and adopt the phenotypic, biochemical, and functional properties of cells unique to other tissues.

Interest has increased in adipose-derived stem cells (ASCs) for tissue engineering, regenerative medicine, biomaterial development, and application. As such, the aim of the present Special Issue is the:

1) Characterization of the physiology of ASCs,

2) Characterization of the secretoma activity of ASCs,

3) Definition of transcriptional and non-transcriptional events related to their commitment, and

4) Application of ASCs as tools to test novel biomaterials for regenerative medicine.

Prof. Dr. Hirofumi Noguchi
Guest Editor

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Keywords

adult stem cells
mesenchymal stem cell
biomaterial
tissue regeneration
tissue engineering
regenerative medicine
implant surfaces
bone regeneration
osseointegration
wound healing

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Published Papers (7 papers)

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Research

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28 pages, 11311 KiB

Open AccessArticle

Activation of Cx43 Hemichannels Induces the Generation of Ca²⁺ Oscillations in White Adipocytes and Stimulates Lipolysis

by Egor A. Turovsky, Elena G. Varlamova and Maria V. Turovskaya

Int. J. Mol. Sci. 2021, 22(15), 8095; https://doi.org/10.3390/ijms22158095 - 28 Jul 2021

Cited by 18 | Viewed by 2883

Abstract

The aim of the study was to investigate the mechanisms of Ca²⁺ oscillation generation upon activation of connexin-43 and regulation of the lipolysis/lipogenesis balance in white adipocytes through vesicular ATP release. With fluorescence microscopy it was revealed that a decrease in the concentration of extracellular calcium ([Ca²⁺]_ex) results in two types of Ca²⁺ responses in white adipocytes: Ca²⁺ oscillations and transient Ca²⁺ signals. It was found that activation of the connexin half-channels is involved in the generation of Ca²⁺ oscillations, since the blockers of the connexin hemichannels—carbenoxolone, octanol, proadifen and Gap26—as well as Cx43 gene knockdown led to complete suppression of these signals. The activation of Cx43 in response to the reduction of [Ca²⁺]_ex was confirmed by TIRF microscopy. It was shown that in response to the activation of Cx43, ATP-containing vesicles were released from the adipocytes. This process was suppressed by knockdown of the Cx43 gene and by bafilomycin A1, an inhibitor of vacuolar ATPase. At the level of intracellular signaling, the generation of Ca²⁺ oscillations in white adipocytes in response to a decrease in [Ca²⁺]_ex occurred due to the mobilization of the Ca²⁺ ions from the thapsigargin-sensitive Ca²⁺ pool of IP₃R as a result of activation of the purinergic P2Y1 receptors and phosphoinositide signaling pathway. After activation of Cx43 and generation of the Ca²⁺ oscillations, changes in the expression levels of key genes and their encoding proteins involved in the regulation of lipolysis were observed in white adipocytes. This effect was accompanied by a decrease in the number of adipocytes containing lipid droplets, while inhibition or knockdown of Cx43 led to inhibition of lipolysis and accumulation of lipid droplets. In this study, we investigated the mechanism of Ca²⁺ oscillation generation in white adipocytes in response to a decrease in the concentration of Ca²⁺ ions in the external environment and established an interplay between periodic Ca²⁺ modes and the regulation of the lipolysis/lipogenesis balance. Full article

(This article belongs to the Special Issue Adipose Stem Cells 3.0)

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18 pages, 4489 KiB

Open AccessArticle

Inflammatory Regulation by TNF-α-Activated Adipose-Derived Stem Cells in the Human Bladder Cancer Microenvironment

by Hui-Kung Ting, Chin-Li Chen, En Meng, Juin-Hong Cherng, Shu-Jen Chang, Chien-Chang Kao, Ming-Hsin Yang, Fang-Shiuan Leung and Sheng-Tang Wu

Int. J. Mol. Sci. 2021, 22(8), 3987; https://doi.org/10.3390/ijms22083987 - 13 Apr 2021

Cited by 16 | Viewed by 3615

Abstract

Mesenchymal stem cells (MSCs), such as adipose-derived stem cells (ADSCs), have the most impressive ability to reduce inflammation through paracrine growth factors and cytokines that participate in inflammation. Tumor necrosis factor (TNF)-α bioactivity is a prerequisite in several inflammatory and autoimmune disease models. This study investigated the effects of TNF-α stimulate on ADSCs in the tumor microenvironment. The RNAseq analysis and cytokines assay demonstrated that TNF-α stimulated ADSCs proliferation and pro-inflammatory genes that correlated to leukocytes differentiation were upregulated. We found that upregulation of TLR2 or PTGS2 toward to IRF7 gene-associated with immunomodulatory and antitumor pathway under TNF-α treatment. In TNF-α-treated ADSCs cultured with the bladder cancer (BC) cell medium, the results showed that apoptosis ratio and OCT-4 and TLR2 genes which maintained the self-renewal ability of stem cells were decreased. Furthermore, the cell survival regulation genes including TRAF1, NF-kB, and IRF7 were upregulated in TNF-α-treated ADSCs. Additionally, these genes have not been upregulated in BC cell medium. A parallel study showed that tumor progressing genes were downregulated in TNF-α-treated ADSCs. Hence, the study suggests that TNF-α enhances the immunomodulatory potential of ADSCs during tumorigenesis and provides insight into highly efficacious MSC-based therapeutic options for BC. Full article

(This article belongs to the Special Issue Adipose Stem Cells 3.0)

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14 pages, 2327 KiB

Open AccessArticle

Characterisation of Novel Angiogenic and Potent Anti-Inflammatory Effects of Micro-Fragmented Adipose Tissue

by Baoqiang Guo, Xenia Sawkulycz, Nima Heidari, Ralph Rogers, Donghui Liu and Mark Slevin

Int. J. Mol. Sci. 2021, 22(6), 3271; https://doi.org/10.3390/ijms22063271 - 23 Mar 2021

Cited by 12 | Viewed by 3315

Abstract

Adipose tissue and more specifically micro-fragmented adipose tissue (MFAT) obtained from liposuction has recently been shown to possess interesting medicinal properties whereby its application supports pain reduction and may enhance tissue regeneration particularly in osteoarthritis. Here we have characterised samples of MFAT produced using the Lipogems^® International Spa system from eight volunteer individuals in order to understand the critical biological mechanisms through which they act. A variation was found in the MFAT cluster size between individual samples and this translated into a similar variation in the ability of purified mesenchymal stem cells (MSCs) to form colony-forming units. Almost all of the isolated cells were CD105/CD90/CD45+ indicating stemness. An analysis of the secretions of cytokines from MFAT samples in a culture using targeted arrays and an enzyme-linked immunosorbent assay (ELISA) showed a long-term specific and significant expression of proteins associated with anti-inflammation (e.g., interleukin-1 receptor alpha (Il-1Rα) antagonist), pro-regeneration (e.g., hepatocyte growth factor), anti-scarring and pro-angiogenesis (e.g., transforming growth factor beta 1 and 2 (TGFβ1/2) and anti-bacterial (e.g., chemokine C-X-C motif ligand-9 (CXCL-9). Angiogenesis and angiogenic signalling were notably increased in primary bovine aortic endothelial cells (BAEC) to a different extent in each individual sample of the conditioned medium whilst a direct capacity of the conditioned medium to block inflammation induced by lipopolysaccharides was shown. This work characterises the biological mechanisms through which a strong, long-lasting, and potentially beneficial effect can be observed regarding pain reduction, protection and regeneration in osteoarthritic joints treated with MFAT. Full article

(This article belongs to the Special Issue Adipose Stem Cells 3.0)

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19 pages, 4158 KiB

Open AccessArticle

CD90 Is Dispensable for White and Beige/Brown Adipocyte Differentiation

by Meike Dahlhaus, Julian Roos, Daniel Engel, Daniel Tews, Daniel Halbgebauer, Jan-Bernd Funcke, Sophie Kiener, Patrick J. Schuler, Johannes Döscher, Thomas K. Hoffmann, Julia Zinngrebe, Markus Rojewski, Hubert Schrezenmeier, Klaus-Michael Debatin, Martin Wabitsch and Pamela Fischer-Posovszky

Int. J. Mol. Sci. 2020, 21(21), 7907; https://doi.org/10.3390/ijms21217907 - 24 Oct 2020

Cited by 3 | Viewed by 2966

Abstract

Brown adipose tissue (BAT) is a thermogenic organ in rodents and humans. In mice, the transplantation of BAT has been successfully used to combat obesity and its comorbidities. While such beneficial properties of BAT are now evident, the developmental and cellular origins of brown, beige, and white adipocytes have remained only poorly understood, especially in humans. We recently discovered that CD90 is highly expressed in stromal cells isolated from human white adipose tissue (WAT) compared to BAT. Here, we studied whether CD90 interferes with brown or white adipogenesis or white adipocyte beiging. We applied flow cytometric sorting of human adipose tissue stromal cells (ASCs), a CRISPR/Cas9 knockout strategy in the human Simpson-Golabi-Behmel syndrome (SGBS) adipocyte model system, as well as a siRNA approach in human approaches supports the hypothesis that CD90 affects brown or white adipogenesis or white adipocyte beiging in humans. Taken together, our findings call the conclusions drawn from previous studies, which claimed a central role of CD90 in adipocyte differentiation, into question. Full article

(This article belongs to the Special Issue Adipose Stem Cells 3.0)

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19 pages, 3462 KiB

Open AccessArticle

IL-4 and SDF-1 Increase Adipose Tissue-Derived Stromal Cell Ability to Improve Rat Skeletal Muscle Regeneration

by Małgorzata Zimowska, Karolina Archacka, Edyta Brzoska, Joanna Bem, Areta M. Czerwinska, Iwona Grabowska, Paulina Kasprzycka, Emilia Michalczewska, Igor Stepaniec, Marta Soszynska, Katarzyna Ilach, Wladyslawa Streminska and Maria A. Ciemerych

Int. J. Mol. Sci. 2020, 21(9), 3302; https://doi.org/10.3390/ijms21093302 - 7 May 2020

Cited by 12 | Viewed by 3421

Abstract

Skeletal muscle regeneration depends on the satellite cells, which, in response to injury, activate, proliferate, and reconstruct damaged tissue. However, under certain conditions, such as large injuries or myopathies, these cells might not sufficiently support repair. Thus, other cell populations, among them adipose tissue-derived stromal cells (ADSCs), are tested as a tool to improve regeneration. Importantly, the pro-regenerative action of such cells could be improved by various factors. In the current study, we tested whether IL-4 and SDF-1 could improve the ability of ADSCs to support the regeneration of rat skeletal muscles. We compared their effect at properly regenerating fast-twitch EDL and poorly regenerating slow-twitch soleus. To this end, ADSCs subjected to IL-4 and SDF-1 were analyzed in vitro and also in vivo after their transplantation into injured muscles. We tested their proliferation rate, migration, expression of stem cell markers and myogenic factors, their ability to fuse with myoblasts, as well as their impact on the mass, structure and function of regenerating muscles. As a result, we showed that cytokine-pretreated ADSCs had a beneficial effect in the regeneration process. Their presence resulted in improved muscle structure and function, as well as decreased fibrosis development and a modulated immune response. Full article

(This article belongs to the Special Issue Adipose Stem Cells 3.0)

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Review

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14 pages, 686 KiB

Open AccessReview

Systematic Review: Allogenic Use of Stromal Vascular Fraction (SVF) and Decellularized Extracellular Matrices (ECM) as Advanced Therapy Medicinal Products (ATMP) in Tissue Regeneration

by Pietro Gentile, Aris Sterodimas, Jacopo Pizzicannella, Laura Dionisi, Domenico De Fazio, Claudio Calabrese and Simone Garcovich

Int. J. Mol. Sci. 2020, 21(14), 4982; https://doi.org/10.3390/ijms21144982 - 15 Jul 2020

Cited by 80 | Viewed by 5139

Abstract

Stromal vascular fraction (SVF) containing adipose stem cells (ASCs) has been used for many years in regenerative plastic surgery for autologous applications, without any focus on their potential allogenic role. Allogenic SVF transplants could be based on the possibility to use decellularized extracellular matrix (ECM) as a scaffold from a donor then re-cellularized by ASCs of the recipient, in order to develop the advanced therapy medicinal products (ATMP) in fully personalized clinical approaches. A systematic review of this field has been realized in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. Multistep research of the PubMed, Embase, MEDLINE, Pre-MEDLINE, PsycINFO, CINAHL, Clinicaltrials.gov, Scopus database, and Cochrane databases has been conducted to identify articles and investigations on human allogenic ASCs transplant for clinical use. Of the 341 articles identified, 313 were initially assessed for eligibility on the basis of the abstract. Of these, only 29 met all the predetermined criteria for inclusion according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach, and 19 have been included in quantitative synthesis (meta-analysis). Ninety-one percent of the studies previously screened (284 papers) were focused on the in vitro results and pre-clinical experiments. The allogenic use regarded the treatment of perianal fistulas, diabetic foot ulcers, knee osteoarthritis, acute respiratory distress syndrome, refractory rheumatoid arthritis, pediatrics disease, fecal incontinence, ischemic heart disease, autoimmune encephalomyelitis, lateral epicondylitis, and soft tissue defects. The information analyzed suggested the safety and efficacy of allogenic ASCs and ECM transplants without major side effects. Full article

(This article belongs to the Special Issue Adipose Stem Cells 3.0)

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23 pages, 1150 KiB

Open AccessReview

Osteochondral Regeneration Using Adipose Tissue-Derived Mesenchymal Stem Cells

by Daiki Murata, Ryota Fujimoto and Koichi Nakayama

Int. J. Mol. Sci. 2020, 21(10), 3589; https://doi.org/10.3390/ijms21103589 - 19 May 2020

Cited by 29 | Viewed by 4511

Abstract

Osteoarthritis (OA) is a major joint disease that promotes locomotor deficiency during the middle- to old-age, with the associated disability potentially decreasing quality of life. Recently, surgical strategies to reconstruct both articular cartilage and subchondral bone for OA have been diligently investigated for restoring joint structure and function. Adipose tissue-derived mesenchymal stem cells (AT-MSCs), which maintain pluripotency and self-proliferation ability, have recently received attention as a useful tool to regenerate osteocartilage for OA. In this review, several studies were described related to AT-MSC spheroids, with scaffold and scaffold-free three-dimensional (3D) constructs produced using “mold” or “Kenzan” methods for osteochondral regeneration. First, several examples of articular cartilage regeneration using AT-MSCs were introduced. Second, studies of osteochondral regeneration (not only cartilage but also subchondral bone) using AT-MSCs were described. Third, examples were presented wherein spheroids were produced using AT-MSCs for cartilage regeneration. Fourth, osteochondral regeneration following autologous implantation of AT-MSC scaffold-free 3D constructs, fabricated using the “mold” or “Kenzan” method, was considered. Finally, prospects of osteochondral regeneration by scaffold-free 3D constructs using AT-MSC spheroids were discussed. Full article

(This article belongs to the Special Issue Adipose Stem Cells 3.0)

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