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Adipose Tissue and Adipose Tissue-Derived Stem Cells in Regenerative Medicine
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Adipose Tissue and Adipose Tissue-Derived Stem Cells in Regenerative Medicine

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

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 8166

Special Issue Editor

Dr. Oliver Heinrich Felthaus

E-Mail Website
Guest Editor
Department of Plastic, Hand and Reconstructive Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany
Interests: mesenchymal stem cells; autologous fat grafting; regeneration; adipose tissue
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The utilization of adipose tissue for the regeneration of soft tissue defects has a long history. Additionally, adipose tissue has been used as a plentiful and easily accessible source of adult mesenchymal stem cells for more than two decades. In recent years, it has been shown that adipose tissue could serve as an optimal biomaterial for regenerative medicine beyond its homologous use in autologous fat grafting. The stem cells derived from adipose tissue can be differentiated into various lineages, have immunomodulatory properties, and secrete various growth factors and cytokines. In addition to soft tissue, bone, and cartilage regeneration and wound healing, adipose tissue-derived stem cells have shown promising results for the treatment of autoimmune and neurodegenerative diseases. Due to their pluripotent differentiation potential, immunosuppressive properties, low immunogenicity, and paracrine activity, there are many possibilities for the clinical application of adipose tissue-derived stem cells in the future.

This Special Issue focuses on recent studies that involve adipose tissue or adipose tissue-derived stem cells in regenerative medicine. Studies that investigate the unique biomaterial properties of adipose tissue for regenerative purposes, as well as those that examine the properties of adipose tissue-derived stem cells and their clinical applications, are within the scope of this Special Issue.

Dr. Oliver Heinrich Felthaus
Guest Editor

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Keywords

  • adipose tissue
  • adipose tissue-derived mesenchymal stem cells
  • adipose-derived stromal cells
  • regenerative medicine
  • cell- and tissue-based therapy
  • tissue engineering

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Published Papers (6 papers)

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Research

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26 pages, 11072 KiB  
Article
Exploring the Potential Effects of Cryopreservation on the Biological Characteristics and Cardiomyogenic Differentiation of Rat Adipose-Derived Mesenchymal Stem Cells
by Ahmed Farag, Sai Koung Ngeun, Masahiro Kaneda, Mohamed Aboubakr, Asmaa Elhaieg, Hanan Hendawy and Ryou Tanaka
Int. J. Mol. Sci. 2024, 25(18), 9908; https://doi.org/10.3390/ijms25189908 - 13 Sep 2024
Viewed by 1078
Abstract
Cryopreservation is essential for the broad clinical application of mesenchymal stem cells (MSCs), yet its impact on their cellular characteristics and cardiomyogenic differentiation potential remains a critical concern in translational medicine. This study aimed to evaluate the effects of cryopreservation on the biological [...] Read more.
Cryopreservation is essential for the broad clinical application of mesenchymal stem cells (MSCs), yet its impact on their cellular characteristics and cardiomyogenic differentiation potential remains a critical concern in translational medicine. This study aimed to evaluate the effects of cryopreservation on the biological properties and cardiomyogenic capacity of rat adipose-derived MSCs (AD-MSCs). We examined their cellular morphology, surface marker expression (CD29, CD90, CD45), trilineage differentiation potential (adipogenic, osteogenic, chondrogenic), and gene expression profiles for the pluripotency marker REX1 and immunomodulatory markers TGFβ1 and IL-6. After inducing cardiomyocyte differentiation, we assessed cardiac-specific gene expressions (Troponin I, MEF2c, GSK-3β) using quantitative RT-qPCR, along with live/dead cell staining and immunofluorescence for cardiac-specific proteins (Troponin T, α-actinin, Myosin Heavy Chain). Cryopreserved AD-MSCs preserved their morphology, surface markers, and differentiation potential, but exhibited a reduced expression of REX1, TGFβ1, and IL-6. Additionally, cryopreservation diminished cardiomyogenic differentiation, as indicated by the lower levels of Troponin I, MEF2c, and GSK-3β seen compared to non-cryopreserved cells. Despite this, high cell viability (>90%) and maintained cardiac protein expression were observed post-cryopreservation. These findings highlight the necessity of optimizing cryopreservation protocols to ensure the full therapeutic potential of AD-MSCs, particularly in applications related to cardiac regenerative medicine. Full article
(This article belongs to the Special Issue Adipose Tissue and Adipose Tissue-Derived Stem Cells in Regenerative Medicine)
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14 pages, 3212 KiB  
Article
A Single Injection of ADRCs Does Not Prevent AAA Formation in Rats in a Randomized Blinded Design
by Egle Kavaliunaite, Pratibha Dhumale, Charlotte Harken Jensen, Søren P. Sheikh, Jes S. Lindholt and Jane Stubbe
Int. J. Mol. Sci. 2024, 25(14), 7591; https://doi.org/10.3390/ijms25147591 - 10 Jul 2024
Viewed by 878
Abstract
There is a pressing need for alternative medical treatments for abdominal aortic aneurysms (AAAs). Mesenchymal regenerative cells derived from adipose tissue (ADRCs) have shown potential in modulating the inflammation and immune responses that drive AAA progression. We hypothesized that ADRCs could reduce inflammation [...] Read more.
There is a pressing need for alternative medical treatments for abdominal aortic aneurysms (AAAs). Mesenchymal regenerative cells derived from adipose tissue (ADRCs) have shown potential in modulating the inflammation and immune responses that drive AAA progression. We hypothesized that ADRCs could reduce inflammation and preserve vascular integrity, potentially slowing the progression of AAA. In our study, subcutaneous adipose tissue was harvested from male Sprague Dawley rats, from which ADRCs were isolated. AAA was induced in these rats using intraluminal porcine pancreatic elastase, followed by intravenous administration of either ADRCs (106 cells) or saline (0.1 mL). We monitored the progression of AAA through weekly ultrasound, and the rats were sacrificed on day 28 for histological analysis. Our results showed no significant difference in the inner abdominal aortic diameter at day 28 between the control group (172% ± 73%, n = 17) and the ADRC-treated group (181% ± 75%, n = 15). Histological analyses of AAA cross-sections also revealed no significant difference in the infiltration of neutrophils or macrophages between the two groups. Furthermore, the integrity and content of elastin in the tunica media were similar between groups. These findings indicate that a single injection of ADRCs does not inhibit the development of AAA in rats in a randomized blinded study. Full article
(This article belongs to the Special Issue Adipose Tissue and Adipose Tissue-Derived Stem Cells in Regenerative Medicine)
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11 pages, 1545 KiB  
Communication
Exosomes from Adipose-Tissue-Derived Stem Cells Induce Proapoptotic Gene Expression in Breast Tumor Cell Line
by Oliver Felthaus, Simon Vedlin, Andreas Eigenberger, Silvan M. Klein and Lukas Prantl
Int. J. Mol. Sci. 2024, 25(4), 2190; https://doi.org/10.3390/ijms25042190 - 12 Feb 2024
Cited by 2 | Viewed by 1493
Abstract
Lipofilling is an option for breast reconstruction after tumor resection to avoid the complications of an implant-based reconstruction. Although some concerns exist regarding the oncological safety of tissue rich in mesenchymal stem cells with their proangiogenic and proliferation-supportive properties, there are also reports [...] Read more.
Lipofilling is an option for breast reconstruction after tumor resection to avoid the complications of an implant-based reconstruction. Although some concerns exist regarding the oncological safety of tissue rich in mesenchymal stem cells with their proangiogenic and proliferation-supportive properties, there are also reports that adipose-tissue-derived stem cells can exhibit antitumoral properties. We isolated primary adipose-tissue-derived stem cells. Both conditioned medium and exosomes were harvested from the cell culture and used to treat the breast cancer cell line MCF-7. Cell viability, cytotoxicity, and gene expression of MCF-7 cells in response to the indirect co-culture were evaluated. MCF-7 cells incubated with exosomes from adipose-tissue-derived stem cells show reduced cell viability in comparison to MCF-7 cells incubated with adipose-tissue-derived stem-cell-conditioned medium. Expression of proapoptotic genes was upregulated, and expression of antiapoptotic genes was downregulated. The debate about the oncological safety of autologous fat grafting after tumor resection continues. Here, we show that exosomes from adipose-tissue-derived stem cells exhibit some antitumoral properties on breast cancer cell line MCF-7. Full article
(This article belongs to the Special Issue Adipose Tissue and Adipose Tissue-Derived Stem Cells in Regenerative Medicine)
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16 pages, 3477 KiB  
Article
Therapeutic Potential of Adipose-Derived Stem Cell-Conditioned Medium and Extracellular Vesicles in an In Vitro Radiation-Induced Skin Injury Model
by Zhixiang Lin, Yoichiro Shibuya, Yukiko Imai, Junya Oshima, Masahiro Sasaki, Kaoru Sasaki, Yukiko Aihara, Vuong Cat Khanh and Mitsuru Sekido
Int. J. Mol. Sci. 2023, 24(24), 17214; https://doi.org/10.3390/ijms242417214 - 7 Dec 2023
Cited by 2 | Viewed by 1842
Abstract
Radiotherapy (RT) is one of three major treatments for malignant tumors, and one of its most common side effects is skin and soft tissue injury. However, the treatment of these remains challenging. Several studies have shown that mesenchymal stem cell (MSC) treatment enhances [...] Read more.
Radiotherapy (RT) is one of three major treatments for malignant tumors, and one of its most common side effects is skin and soft tissue injury. However, the treatment of these remains challenging. Several studies have shown that mesenchymal stem cell (MSC) treatment enhances skin wound healing. In this study, we extracted human dermal fibroblasts (HDFs) and adipose-derived stem cells (ADSCs) from patients and generated an in vitro radiation-induced skin injury model with HDFs to verify the effect of conditioned medium derived from adipose-derived stem cells (ADSC-CM) and extracellular vesicles derived from adipose-derived stem cells (ADSC-EVs) on the healing of radiation-induced skin injury. The results showed that collagen synthesis was significantly increased in wounds treated with ADSC-CM or ADSC-EVs compared with the control group, which promoted the expression of collagen-related genes and suppressed the expression of inflammation-related genes. These findings indicated that treatment with ADSC-CM or ADSC-EVs suppressed inflammation and promoted extracellular matrix deposition; treatment with ADSC-EVs also promoted fibroblast proliferation. In conclusion, these results demonstrate the effectiveness of ADSC-CM and ADSC-EVs in the healing of radiation-induced skin injury. Full article
(This article belongs to the Special Issue Adipose Tissue and Adipose Tissue-Derived Stem Cells in Regenerative Medicine)
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13 pages, 2184 KiB  
Article
Cadaveric Adipose-Derived Stem Cells for Regenerative Medicine and Research
by Lara Milián, Pilar Molina, María Oliver-Ferrándiz, Carlos Fernández-Sellers, Ana Monzó, Rafael Sánchez-Sánchez, Aitana Braza-Boils, Manuel Mata and Esther Zorio
Int. J. Mol. Sci. 2023, 24(21), 15696; https://doi.org/10.3390/ijms242115696 - 28 Oct 2023
Cited by 2 | Viewed by 1487
Abstract
Advances in regenerative medicine have enabled the search for new solutions to current health problems in so far unexplored fields. Thus, we focused on cadaveric subcutaneous fat as a promising source of adipose-derived stem cells (ADSCs) that have potential to differentiate into different [...] Read more.
Advances in regenerative medicine have enabled the search for new solutions to current health problems in so far unexplored fields. Thus, we focused on cadaveric subcutaneous fat as a promising source of adipose-derived stem cells (ADSCs) that have potential to differentiate into different cell lines. With this aim, we isolated and characterized ADSCs from cadaveric samples with a postmortem interval ranging from 30 to 55 h and evaluated their ability to differentiate into chondrocytes or osteocytes. A commercial ADSC line was used as reference. Morphological and protein expression analyses were used to confirm the final stage of differentiation. Eight out of fourteen samples from patients were suitable to complete the whole protocol. Cadaveric ADSCs exhibited features of stem cells based upon several markers: CD29 (84.49 ± 14.07%), CD105 (94.38 ± 2.09%), and CD44 (99.77 ± 0.32%). The multiparametric assessment of differentiation confirmed the generation of stable lines of chondrocytes and osteocytes. In conclusion, we provide evidence supporting the feasibility of obtaining viable postmortem human subcutaneous fat ADSCs with potential application in tissue engineering and research fields. Full article
(This article belongs to the Special Issue Adipose Tissue and Adipose Tissue-Derived Stem Cells in Regenerative Medicine)
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Review

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15 pages, 1247 KiB  
Review
Adipose-Derived Stromal Cells and Cancer-Associated Fibroblasts: Interactions and Implications in Tumor Progression
by Rasha S. Abo El Alaa, Wafaa Al-Mannai, Nour Darwish and Layla Al-Mansoori
Int. J. Mol. Sci. 2024, 25(21), 11558; https://doi.org/10.3390/ijms252111558 - 28 Oct 2024
Viewed by 598
Abstract
Adipose-derived stromal cells (ASCs) and cancer-associated fibroblasts (CAFs) play pivotal roles in the tumor microenvironment (TME), significantly influencing cancer progression and metastasis. This review explores the plasticity of ASCs, which can transdifferentiate into CAFs under the influence of tumor-derived signals, thus enhancing their [...] Read more.
Adipose-derived stromal cells (ASCs) and cancer-associated fibroblasts (CAFs) play pivotal roles in the tumor microenvironment (TME), significantly influencing cancer progression and metastasis. This review explores the plasticity of ASCs, which can transdifferentiate into CAFs under the influence of tumor-derived signals, thus enhancing their secretion of extracellular matrix components and pro-inflammatory cytokines that promote tumorigenesis. We discuss the critical process of the epithelial-to-mesenchymal transition (EMT) facilitated by ASCs and CAFs, highlighting its implications for increased invasiveness and therapeutic resistance in cancer cells. Key signaling pathways, including the transforming growth factor-β (TGF-β), Wnt/β-catenin, and Notch, are examined for their roles in regulating EMT and CAF activation. Furthermore, we address the impact of epigenetic modifications on ASC and CAF functionality, emphasizing recent advances in targeting these modifications to inhibit their pro-tumorigenic effects. This review also considers the metabolic reprogramming of ASCs and CAFs, which supports their tumor-promoting activities through enhanced glycolytic activity and lactate production. Finally, we outline potential therapeutic strategies aimed at disrupting the interactions between ASCs, CAFs, and tumor cells, including targeted inhibitors of key signaling pathways and innovative immunotherapy approaches. By understanding the complex roles of ASCs and CAFs within the TME, this review aims to identify new therapeutic opportunities that could improve patient outcomes in cancer treatment. Full article
(This article belongs to the Special Issue Adipose Tissue and Adipose Tissue-Derived Stem Cells in Regenerative Medicine)
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