New Insights into Adipose-Derived Stem Cells (ADSCs)

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 10231

Special Issue Editors


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Guest Editor
Department of Reconstructive Surgery and Hand Surgery, AOU delle Marche, Ancona, Italy
Interests: plastic surgery; aesthetic surgery; reconstructive surgery; breast reconstruction; regenerative surgery; hand surgery
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
School of Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
Interests: stem cells; tissue engineering; extracellular vesicles; biomaterials; cryopreservation; clinical translation

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Guest Editor
School of Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
Interests: stem cells; tissue engineering; extracellular vesicles; biomaterials; immunology; ageing; extracellular matrix
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Adipose-derived stem cells (ASCs) hold promise for a myriad of regenerative medicine applications. Isolated from ubiquitous and clinically accessible adipose tissue reservoirs, ASCs exhibit the capacity for multipotent differentiation into adipocyte, chondrocyte, and osteocyte lineages. Notably, ASCs possess distinctive immunomodulatory properties, underscoring their potential for use in treating autoimmune disorders as well as coordinating the immune response to foster tissue repair. Recent investigations have unveiled their intricate paracrine signaling mechanisms and their role in angiogenesis, implicating ASCs to be key orchestrators of regenerative processes.

This Special Issue aims to unravel the latest discoveries and advancements in the field of adipose-derived stem cells, including original research articles and comprehensive reviews that explore the molecular mechanisms governing adipogenic differentiation, immunomodulatory properties, paracrine signaling, and their clinical implications. With a focus on bridging the gap between fundamental research and clinical translation, this Special Issue also offers a platform with which to showcase emerging therapeutics utilizing ASCs, including ASC-based cell therapies, ASC-derived exosomes, and ASC-based tissue-engineered constructs, as well as efforts focused on streamlining the manufacturing and implementation of these therapeutics.

Dr. Francesco De Francesco
Dr. Arthi Shridhar
Dr. William D’Angelo
Guest Editors

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Keywords

  • adipose-derived stem cells
  • immunomodulation
  • exosomes
  • cell therapy
  • clinical translation

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Published Papers (4 papers)

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27 pages, 6880 KiB  
Article
Deciphering the Transcriptional Metabolic Profile of Adipose-Derived Stem Cells During Osteogenic Differentiation and Epigenetic Drug Treatment
by Giulia Gerini, Alice Traversa, Fabrizio Cece, Matteo Cassandri, Paola Pontecorvi, Simona Camero, Giulia Nannini, Enrico Romano, Francesco Marampon, Mary Anna Venneri, Simona Ceccarelli, Antonio Angeloni, Amedeo Amedei, Cinzia Marchese and Francesca Megiorni
Cells 2025, 14(2), 135; https://doi.org/10.3390/cells14020135 - 17 Jan 2025
Cited by 1 | Viewed by 1147
Abstract
Adipose-derived mesenchymal stem cells (ASCs) are commonly employed in clinical treatment for various diseases due to their ability to differentiate into multi-lineage and anti-inflammatory/immunomodulatory properties. Preclinical studies support their use for bone regeneration, healing, and the improvement of functional outcomes. However, a deeper [...] Read more.
Adipose-derived mesenchymal stem cells (ASCs) are commonly employed in clinical treatment for various diseases due to their ability to differentiate into multi-lineage and anti-inflammatory/immunomodulatory properties. Preclinical studies support their use for bone regeneration, healing, and the improvement of functional outcomes. However, a deeper understanding of the molecular mechanisms underlying ASC biology is crucial to identifying key regulatory pathways that influence differentiation and enhance regenerative potential. In this study, we employed the NanoString nCounter technology, an advanced multiplexed digital counting method of RNA molecules, to comprehensively characterize differentially expressed transcripts involved in metabolic pathways at distinct time points in osteogenically differentiating ASCs treated with or without the pan-DNMT inhibitor RG108. In silico annotation and gene ontology analysis highlighted the activation of ethanol oxidation, ROS regulation, retinoic acid metabolism, and steroid hormone metabolism, as well as in the metabolism of lipids, amino acids, and nucleotides, and pinpointed potential new osteogenic drivers like AOX1 and ADH1A. RG108-treated cells, in addition to the upregulation of the osteogenesis-related markers RUNX2 and ALPL, showed statistically significant alterations in genes implicated in transcriptional control (MYCN, MYB, TP63, and IRF1), ethanol oxidation (ADH1C, ADH4, ADH6, and ADH7), and glucose metabolism (SLC2A3). These findings highlight the complex interplay of the metabolic, structural, and signaling pathways that orchestrate osteogenic differentiation. Furthermore, this study underscores the potential of epigenetic drugs like RG108 to enhance ASC properties, paving the way for more effective and personalized cell-based therapies for bone regeneration. Full article
(This article belongs to the Special Issue New Insights into Adipose-Derived Stem Cells (ADSCs))
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14 pages, 3244 KiB  
Article
Adipose-Derived Mesenchymal Stem Cells (ADSCs) Have Anti-Fibrotic Effects on Lung Fibroblasts from Idiopathic Pulmonary Fibrosis (IPF) Patients
by Noriko Ouji-Sageshima, Aiko Hiyama, Makiko Kumamoto, Masahiro Kitabatake, Atsushi Hara, Ryutaro Furukawa, Shigeto Hontsu, Takeshi Kawaguchi, Noriyoshi Sawabata, Shigeo Muro and Toshihiro Ito
Cells 2024, 13(24), 2050; https://doi.org/10.3390/cells13242050 - 12 Dec 2024
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Abstract
Idiopathic pulmonary fibrosis (IPF) is the most common type of fibrosis in lungs, characterized as a chronic and progressive interstitial lung disease involving pathological findings of fibrosis with a median survival of 3 years. Despite the knowledge accumulated regarding IPF from basic and [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is the most common type of fibrosis in lungs, characterized as a chronic and progressive interstitial lung disease involving pathological findings of fibrosis with a median survival of 3 years. Despite the knowledge accumulated regarding IPF from basic and clinical research, an effective medical therapy for the condition remains to be established. Thus, it is necessary for further research, including stem cell therapy, which will provide new insights into and expectations for IPF treatment. Recently, it has been reported that one of the new therapeutic candidates for IPF is adipose-derived mesenchymal stem cells (ADSCs), which have several benefits, such as easy accessibility and minimal morbidity compared to bone marrow-derived mesenchymal stem cells. Therefore, we investigated the possibility of ADSCs as a therapeutic candidate for IPF. Using human lung fibroblasts (LFs) from IPF patients, we demonstrated that human IPF LFs cocultured with ADSCs led to reduced fibrosis-related genes. Further analysis revealed that ADSCs prevented the activation of the ERK signaling pathway in IPF LFs via the upregulation of protein tyrosine phosphatase receptor-type R (PTPRR), which negatively regulates the ERK signaling pathway. Moreover, we demonstrated that intravascular administration of ADSCs improved the pathogenesis of bleomycin-induced pulmonary fibrosis with reduced collagen deposition in histology and hydroxyproline quantification and collagen markers such as the gene expression of types I and III collagen and α-smooth muscle actin (α-SMA) in a murine model. ADSC transfer was also investigated in a humanized mouse model of lung fibrosis induced via the infusion of human IPF LFs, because the bleomycin installation model does not fully recapitulate the pathogenesis of IPF. Using the humanized mouse model, we found that intravascular administration of ADSCs also improved fibrotic changes in the lungs. These findings suggest that ADSCs are a promising therapeutic candidate for IPF. Full article
(This article belongs to the Special Issue New Insights into Adipose-Derived Stem Cells (ADSCs))
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18 pages, 3943 KiB  
Article
Transcriptional Control of Subcutaneous Adipose Tissue by the Transcription Factor CTCF Modulates Heterogeneity in Fat Distribution in Women
by Edina Erdos, Katalin Sandor, Crystal L. Young-Erdos, Laszlo Halasz, Steven R. Smith, Timothy F. Osborne and Adeline Divoux
Cells 2024, 13(1), 86; https://doi.org/10.3390/cells13010086 - 30 Dec 2023
Cited by 3 | Viewed by 2518
Abstract
Determining the mechanism driving body fat distribution will provide insights into obesity-related health risks. We used functional genomics tools to profile the epigenomic landscape to help infer the differential transcriptional potential of apple- and pear-shaped women’s subcutaneous adipose-derived stem cells (ADSCs). We found [...] Read more.
Determining the mechanism driving body fat distribution will provide insights into obesity-related health risks. We used functional genomics tools to profile the epigenomic landscape to help infer the differential transcriptional potential of apple- and pear-shaped women’s subcutaneous adipose-derived stem cells (ADSCs). We found that CCCTC-binding factor (CTCF) expression and its chromatin binding were increased in ADSCs from pear donors compared to those from apple donors. Interestingly, the pear enriched CTCF binding sites were located predominantly at the active transcription start sites (TSSs) of genes with active histone marks and YY1 motifs and were also associated with pear enriched RNAPII binding. In contrast, apple enriched CTCF binding sites were mainly found at intergenic regions and when identified at TSS, they were enriched with the bivalent chromatin signatures. Altogether, we provide evidence that CTCF plays an important role in differential regulation of subcutaneous ADSCs gene expression and may influence the development of apple vs. pear body shape. Full article
(This article belongs to the Special Issue New Insights into Adipose-Derived Stem Cells (ADSCs))
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13 pages, 2199 KiB  
Commentary
The Evolution of Current Concept of the Reconstructive Ladder in Plastic Surgery: The Emerging Role of Translational Medicine
by Francesco De Francesco, Nicola Zingaretti, Pier Camillo Parodi and Michele Riccio
Cells 2023, 12(21), 2567; https://doi.org/10.3390/cells12212567 - 3 Nov 2023
Cited by 7 | Viewed by 4189
Abstract
Plastic surgeons have used the reconstructive ladder for many decades as a standard directory for complex trauma reconstruction with the goal of repairing body structures and restoring functionality. This consists of different surgical maneuvers, such as secondary intention and direct tissue closure, as [...] Read more.
Plastic surgeons have used the reconstructive ladder for many decades as a standard directory for complex trauma reconstruction with the goal of repairing body structures and restoring functionality. This consists of different surgical maneuvers, such as secondary intention and direct tissue closure, as well as more complex methods such as local tissue transfer and free flap. The reconstructive ladder represents widely known options achievable for tissue reconstruction and wound closure that puts at the bottom rung the simplest methods of reconstruction and strengthens the complexity by moving upward. Regenerative medicine and surgery constitute a quickly spreading area of translational research that can be employed by minimally invasive surgical strategies, with the aim of regenerating cells and tissues in vivo in order to reestablish normal function through the intrinsic potential of cells, in combination with biomaterials and appropriate biochemical stimuli. These translational procedures have the aim of creating an appropriate microenvironment capable of supporting the physiological cellular function to generate the desired cells or tissues and to generate parenchymal, stromal, and vascular components on demand, and above all to produce intelligent materials capable of determining the fate of cells. Smart technologies have been grown that give extra “rungs” on the classic reconstructive ladder to integrate a more holistic, patient-based approach with improved outcomes. This commentary presents the evolution of the traditional concept of the reconstructive ladder in the field of plastic surgery into a new course with the aim of achieving excellent results for soft tissue reconstruction by applying innovative technologies and biologically active molecules for a wide range of surgical diseases. Full article
(This article belongs to the Special Issue New Insights into Adipose-Derived Stem Cells (ADSCs))
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