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Nishiguchi Y, Ueda M, Kubo H, Jo JI, Hashimoto Y, Takenobu T. Optimized human dedifferentiated fat cells from the buccal fat pad-derived osteoinductive extracellular vesicles promote osteoblast differentiation. J Dent Sci 2025; 20:278-285. [PMID: 39873097 PMCID: PMC11763207 DOI: 10.1016/j.jds.2024.07.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 07/25/2024] [Indexed: 01/30/2025] Open
Abstract
Background/purpose Bone reconstruction in the maxillofacial region typically relies on autologous bone grafting, which presents challenges, including donor site complications and graft limitations. Recent advances in tissue engineering have identified highly pure and proliferative dedifferentiated fat cells (DFATs) as promising alternatives. Herein, we explored the capacity for osteoblast differentiation and the osteoinductive characteristics of extracellular vesicles derived from DFATs (DFAT-EVs). Materials and methods DFATs were isolated from human buccal fat pads, cultured to confluency, and placed in either a standard or osteogenic induction medium. After culturing for 3 days, the conditioned medium was used to generate EVs using the size-exclusion chromatography and concentration filter method. Results Characterization of DFAT-EVs revealed typical EV morphology and positive markers (CD9 and CD63), with no differences between the two groups. In vitro assays demonstrated that EVs derived from the osteogenic induction medium (OI-EVs) significantly increased alkaline phosphatase activity and osteogenesis-related genes (Runx2 and collagen type I) compared to control EVs. Next-generation sequencing identified differentially expressed miRNAs, and gene ontology analysis suggested pathways involved in osteoblast differentiation. Conclusion Isolating DFATs from buccal fat pads under osteogenic induction conditions offers a procedure confined to the oral cavity, eliminating the need for harvesting from other sites. Thus, DFAT-EVs hold promise for promoting bone regeneration in maxillofacial applications.
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Affiliation(s)
- Yusuke Nishiguchi
- Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, Osaka, Japan
| | - Mamoru Ueda
- Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, Osaka, Japan
| | - Hirohito Kubo
- Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, Osaka, Japan
| | - Jun-Ichiro Jo
- Department of Biomaterials, Osaka Dental University, Osaka, Japan
| | | | - Toshihiko Takenobu
- Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, Osaka, Japan
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Xue M, Liao Y, Jiang W. Insights into the molecular changes of adipocyte dedifferentiation and its future research opportunities. J Lipid Res 2024; 65:100644. [PMID: 39303983 PMCID: PMC11550672 DOI: 10.1016/j.jlr.2024.100644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 08/23/2024] [Accepted: 09/14/2024] [Indexed: 09/22/2024] Open
Abstract
Recent studies have challenged the traditional belief that mature fat cells are irreversibly differentiated and revealed they can dedifferentiate into fibroblast-like cells known as dedifferentiated fat (DFAT) cells. Resembling pluripotent stem cells, DFAT cells hold great potential as a cell source for stem cell therapy. However, there is limited understanding of the specific changes that occur following adipocyte dedifferentiation and the detailed regulation of this process. This review explores the epigenetic, genetic, and phenotypic alterations associated with DFAT cell dedifferentiation, identifies potential targets for clinical regulation and discusses the current applications and challenges in the field of DFAT cell research.
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Affiliation(s)
- Mingheng Xue
- Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yunjun Liao
- Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
| | - Wenqing Jiang
- Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
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Caruso JA, Wang X, Murrow LM, Rodriguez CI, Chen-Tanyolac C, Vu L, Chen YY, Gascard P, Gartner ZJ, Kerlikowske K, Tlsty TD. Loss of PPARγ activity characterizes early protumorigenic stromal reprogramming and dictates the therapeutic window of opportunity. Proc Natl Acad Sci U S A 2023; 120:e2303774120. [PMID: 37816052 PMCID: PMC10589683 DOI: 10.1073/pnas.2303774120] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 08/31/2023] [Indexed: 10/12/2023] Open
Abstract
Although robustly expressed in the disease-free (DF) breast stroma, CD36 is consistently absent from the stroma surrounding invasive breast cancers (IBCs). In this study, we primarily observed CD36 expression in adipocytes and intralobular capillaries within the DF breast. Larger vessels concentrated in interlobular regions lacked CD36 and were instead marked by the expression of CD31. When evaluated in perilesional capillaries surrounding ductal carcinoma in situ, a nonobligate IBC precursor, CD36 loss was more commonly observed in lesions associated with subsequent IBC. Peroxisome proliferator-activated receptor γ (PPARγ) governs the expression of CD36 and genes involved in differentiation, metabolism, angiogenesis, and inflammation. Coincident with CD36 loss, we observed a dramatic suppression of PPARγ and its target genes in capillary endothelial cells (ECs) and pericytes, which typically surround and support the stability of the capillary endothelium. Factors present in conditioned media from malignant cells repressed PPARγ and its target genes not only in cultured ECs and pericytes but also in adipocytes, which require PPARγ for proper differentiation. In addition, we identified a role for PPARγ in opposing the transition of pericytes toward a tumor-supportive myofibroblast phenotype. In mouse xenograft models, early intervention with rosiglitazone, a PPARγ agonist, demonstrated significant antitumor effects; however, following the development of a palpable tumor, the antitumor effects of rosiglitazone were negated by the repression of PPARγ in the mouse stroma. In summary, PPARγ activity in healthy tissues places several stromal cell types in an antitumorigenic state, directly inhibiting EC proliferation, maintaining adipocyte differentiation, and suppressing the transition of pericytes into tumor-supportive myofibroblasts.
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Affiliation(s)
- Joseph A Caruso
- Department of Pathology, University of California, San Francisco, CA 94143
| | - Xianhong Wang
- Department of Pathology, University of California, San Francisco, CA 94143
| | - Lyndsay M Murrow
- Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143
| | | | | | - Lisa Vu
- Department of Medicine and Epidemiology and Biostatistics, University of California, San Francisco, CA 94143
| | - Yunn-Yi Chen
- Department of Pathology, University of California, San Francisco, CA 94143
| | - Philippe Gascard
- Department of Pathology, University of California, San Francisco, CA 94143
| | - Zev J Gartner
- Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143
| | - Karla Kerlikowske
- Department of Medicine and Epidemiology and Biostatistics, University of California, San Francisco, CA 94143
| | - Thea D Tlsty
- Department of Pathology, University of California, San Francisco, CA 94143
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Liang Z, He Y, Tang H, Li J, Cai J, Liao Y. Dedifferentiated fat cells: current applications and future directions in regenerative medicine. Stem Cell Res Ther 2023; 14:207. [PMID: 37605289 PMCID: PMC10441730 DOI: 10.1186/s13287-023-03399-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 06/13/2023] [Indexed: 08/23/2023] Open
Abstract
Stem cell therapy is the most promising treatment option for regenerative medicine. Therapeutic effect of different stem cells has been verified in various disease model. Dedifferentiated fat (DFAT) cells, derived from mature adipocytes, are induced pluripotent stem cells. Compared with ASCs and other stem cells, the DFAT cells have unique advantageous characteristics in their abundant sources, high homogeneity, easily harvest and low immunogenicity. The DFAT cells have shown great potential in tissue engineering and regenerative medicine for the treatment of clinical problems such as cardiac and kidney diseases, autoimmune disease, soft and hard tissue defect. In this review, we summarize the current understanding of DFAT cell properties and focus on the relevant practical applications of DFAT cells in cell therapy in recent years.
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Affiliation(s)
- Zhuokai Liang
- Department of Plastic and Reconstructive Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yufei He
- Department of Plastic and Reconstructive Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Haojing Tang
- Department of Plastic and Reconstructive Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jian Li
- Department of Plastic and Reconstructive Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Junrong Cai
- Department of Plastic and Reconstructive Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
| | - Yunjun Liao
- Department of Plastic and Reconstructive Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
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Wang J, Cai J, Zhang Q, Wen J, Liao Y, Lu F. Fat transplantation induces dermal adipose regeneration and reverses skin fibrosis through dedifferentiation and redifferentiation of adipocytes. Stem Cell Res Ther 2022; 13:499. [PMID: 36210466 PMCID: PMC9549649 DOI: 10.1186/s13287-022-03127-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 08/07/2022] [Indexed: 11/18/2022] Open
Abstract
Background Localized scleroderma causes cosmetic disfigurement, joint contractures, and other functional impairment, but no currently available medications can reverse the resulting skin lesions. Fat grafting is beneficial for reversing skin fibrosis; however, the mechanism by which adipose tissue transplantation contributes to lesion improvement has not been fully clarified. The purpose of our study was to verify the therapeutic effect of fat grafts in reversing skin fibrosis. Methods Inguinal fat pads from AdipoqCreER+;mT/mG mice, which were treated with tamoxifen, were transplanted to the skin lesion in bleomycin-treated wild-type C57 mice. Tdtomato transgenic mice-derived adipocytes, adipose-derived stem cells (ASCs), dedifferentiated adipocytes (DAs) were embedded in matrigel and transplanted beneath the skin lesion of bleomycin-treated wild-type C57 mice. A transwell co‐culture system was used to verify the effect of ASCs, adipocytes or DAs on scleroderma fibroblasts or monocytes. Results Adipocytes from the fat grafts could undergo dedifferentiation and redifferentiation for dermal adipose tissue re-accumulation within the skin lesion. Moreover, compared with ASCs and adipocytes, DAs show greater potency of inducing adipogenesis. ASCs and DAs showed comparable effect on inducing angiogenesis and suppressing macrophage infiltration in fibrotic skin. Co-culture assay showed that DAs and ASCs were able to reduce fibrosis-related genes in human scleroderma fibroblasts and drive M2 macrophage polarization. Conclusion Our results indicated that adipocytes would transform into a more functional and dedifferentiated state and reverse dermal fibrosis, by promoting dermal adipose tissue regeneration, improving angiogenesis, suppressing macrophage-mediated inflammation and myofibroblast accumulation.
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Côté JA, Ostinelli G, Gauthier MF, Lacasse A, Tchernof A. Focus on dedifferentiated adipocytes: characteristics, mechanisms, and possible applications. Cell Tissue Res 2019; 378:385-398. [PMID: 31289929 DOI: 10.1007/s00441-019-03061-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Accepted: 06/06/2019] [Indexed: 02/06/2023]
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Kishimoto N, Honda Y, Momota Y, Tran SD. Dedifferentiated Fat (DFAT) cells: A cell source for oral and maxillofacial tissue engineering. Oral Dis 2018; 24:1161-1167. [PMID: 29356251 DOI: 10.1111/odi.12832] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2017] [Revised: 01/14/2018] [Accepted: 01/16/2018] [Indexed: 12/26/2022]
Abstract
Tissue engineering is a promising method for the regeneration of oral and maxillofacial tissues. Proper selection of a cell source is important for the desired application. This review describes the discovery and usefulness of dedifferentiated fat (DFAT) cells as a cell source for tissue engineering. Dedifferentiated Fat cells are a highly homogeneous cell population (high purity), highly proliferative, and possess a multilineage potential for differentiation into various cell types under proper in vitro inducing conditions and in vivo. Moreover, DFAT cells have a higher differentiation capability of becoming osteoblasts, chondrocytes, and adipocytes than do bone marrow-derived mesenchymal stem cells and/or adipose tissue-derived stem cells. The usefulness of DFAT cells in vivo for periodontal tissue, bone, peripheral nerve, muscle, cartilage, and fat tissue regeneration was reported. Dedifferentiated Fat cells obtained from the human buccal fat pad (BFP) are a minimally invasive procedure with limited esthetic complications for patients. The BFP is a convenient and accessible anatomical site to harvest DFAT cells for dentists and oral surgeons, and thus is a promising cell source for oral and maxillofacial tissue engineering.
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Affiliation(s)
- N Kishimoto
- Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, Montreal, Quebec, Canada
| | - Y Honda
- Institute of Dental Research, Osaka Dental University, Osaka, Japan
| | - Y Momota
- Department of Anesthesiology, Osaka Dental University, Osaka, Japan
| | - S D Tran
- Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, Montreal, Quebec, Canada
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Tsurumachi N, Akita D, Kano K, Matsumoto T, Toriumi T, Kazama T, Oki Y, Saito-Tamura Y, Tonogi M, Shimizu N, Honda M. Effect of collagenase concentration on the isolation of small adipocytes from human buccal fat pad. J Oral Sci 2018; 60:14-23. [PMID: 29479028 DOI: 10.2334/josnusd.16-0786] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
Dedifferentiated fat (DFAT) cells were isolated from mature adipocytes using the ceiling culture method. Recently, we successfully isolated DFAT cells from adipocytes with a relatively small size (<40 μm). DFAT cells have a higher osteogenic potential than that of medium adipocytes. Therefore, the objective of this study was to determine the optimal concentration of collagenase solution for isolating small adipocytes from human buccal fat pads (BFPs). Four concentrations of collagenase solution (0.01%, 0.02%, 0.1%, and 0.5%) were used, and their effectiveness was assessed by the number of small adipocytes and DFAT cells isolated. The total number of floating adipocytes that dissociated with 0.02% collagenase was 2.5 times of that dissociated with 0.1% collagenase. The number of floating adipocytes with a diameter of ≤29 μm that dissociated with 0.02% collagenase was thrice of those dissociated with 0.1% and 0.5% collagenase. The number of DFAT cells that dissociated with 0.02% collagenase was 1.5 times of that dissociated with 0.1% collagenase. In addition, DFAT cells that dissociated with 0.02% collagenase had a higher osteogenic differentiation potential than those that dissociated with 0.1% collagenase. These results suggest that 0.02% is the optimal collagenase concentration for isolating small adipocytes from BFPs.
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Affiliation(s)
- Niina Tsurumachi
- Department of Orthodontics, Nihon University School of Dentistry
| | - Daisuke Akita
- Department of Partial Denture Prosthodontics, Nihon University School of Dentistry
| | - Koichiro Kano
- Laboratory of Cell and Tissue Biology, College of Bioresource Sciences, Nihon University
| | - Taro Matsumoto
- Department of Functional Morphology Division of Cell Regeneration and Transplantation, Nihon University School of Medicine
| | - Taku Toriumi
- Department of Anatomy, Nihon University School of Dentistry
| | - Tomohiko Kazama
- Department of Functional Morphology Division of Cell Regeneration and Transplantation, Nihon University School of Medicine
| | - Yoshinao Oki
- Laboratory of Cell and Tissue Biology, College of Bioresource Sciences, Nihon University
| | | | - Morio Tonogi
- Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry
| | | | - Masaki Honda
- Department of Oral Anatomy, Aichi Gakuin University School of Dentistry
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9
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hASC and DFAT, Multipotent Stem Cells for Regenerative Medicine: A Comparison of Their Potential Differentiation In Vitro. Int J Mol Sci 2017; 18:ijms18122699. [PMID: 29236047 PMCID: PMC5751300 DOI: 10.3390/ijms18122699] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Revised: 11/23/2017] [Accepted: 12/09/2017] [Indexed: 01/01/2023] Open
Abstract
Adipose tissue comprises both adipose and non-adipose cells such as mesenchymal stem cells. These cells show a surface antigenic profile similar to that of bone-marrow-derived MSC. The cells derived from the dedifferentiation of mature adipocytes (DFAT) are another cell population with characteristics of stemness. The aim of this study is to provide evidence of the stemness, proliferation, and differentiation of human adipose stem cells (hASC) and DFAT obtained from human subcutaneous AT and evaluate their potential use in regenerative medicine. Cell populations were studied by histochemical and molecular biology techniques. Both hASC and DFAT were positive for MSC markers. Their proliferative capacity was similar and both populations were able to differentiate into osteogenic, chondrogenic, and adipogenic lineages. DFAT were able to accumulate lipids and their lipoprotein lipase and adiponectin gene expression were high. Alkaline phosphatase and RUNX2 gene expression were greater in hASC than in DFAT at 14 days but became similar after three weeks. Both cell populations were able to differentiate into chondrocytes, showing positive staining with Alcian Blue and gene expression of SOX9 and ACAN. In conclusion, both hASC and DFAT populations derived from AT have a high differentiation capacity and thus may have applications in regenerative medicine.
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Wang Z, Jia Y, Du F, Chen M, Dong X, Chen Y, Huang W. IL-17A Inhibits Osteogenic Differentiation of Bone Mesenchymal Stem Cells via Wnt Signaling Pathway. Med Sci Monit 2017; 23:4095-4101. [PMID: 28837545 PMCID: PMC5580517 DOI: 10.12659/msm.903027] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Interleukin-17A (IL-17A) is not only an important modulator of inflammatory reactions, but also affects bone metabolism, which is involved in osteogenic differentiation of stem cells. However, the role and mechanism of IL-17A in osteogenic differentiation of bone mesenchymal stem cells (BMSCs) are not fully understood. In this study, we investigated the role and mechanism of IL-17A in osteogenic differentiation of BMSCs. Material/Methods The osteogenic differentiation of BMSCs was induced by osteoblast-induction medium with IL-17A or without IL-17A. The osteogenic differentiation of BMSCs was confirmed by the alkaline phosphatase and alizarin red staining. The lentiviral plasmid was used to construct the sFRP1-shRNA expression vector. The associated osteogenic differentiation marks (RUNX2, ALP, OPN), Wnt signaling pathway inhibitor (sFRP1), and modulators of Wnt signaling pathway (Wnt3, Wnt6) were detected by qRT-PCR and Western blot method. Results The results showed that the addition of IL-17A inhibited osteogenic differentiation of BMSCs. IL-17A induced up-regulated expression of sFRP1 and down-regulated expression of Wnt3 and Wnt6 in BMSCs. In addition, sFRP1-shRNA abolished the inhibition effect of IL-17A in osteogenic differentiation of BMSCs and induced up-regulated expression of Wnt3 and Wnt6 in the Wnt signaling pathway in BMSCs. Conclusions Our findings show that IL-17A inhibits osteogenic differentiation of bone mesenchymal stem cells via the Wnt signaling pathway.
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Affiliation(s)
- Zhenguo Wang
- Department of Stomatology, The 1st Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China (mainland)
| | - Ying Jia
- Department of Stomatology, The 1st Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China (mainland)
| | - Fu Du
- Jindian Dendure Chain Group, Chengdu, Sichuan, China (mainland)
| | - Min Chen
- Department of Stomatology, The 1st Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China (mainland)
| | - Xiuhua Dong
- Department of Stomatology, The 1st Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China (mainland)
| | - Yan Chen
- Department of Stomatology, The 1st Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China (mainland)
| | - Wen Huang
- Department of Anesthesiology, The 1st Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China (mainland)
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Buccal Fat Pad as a Potential Source of Stem Cells for Bone Regeneration: A Literature Review. Stem Cells Int 2017; 2017:8354640. [PMID: 28757880 PMCID: PMC5516750 DOI: 10.1155/2017/8354640] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2016] [Revised: 04/17/2017] [Accepted: 05/16/2017] [Indexed: 12/21/2022] Open
Abstract
Adipose tissues hold great promise in bone tissue engineering since they are available in large quantities as a waste material. The buccal fat pad (BFP) is a specialized adipose tissue that is easy to harvest and contains a rich blood supply, and its harvesting causes low complications for patients. This review focuses on the characteristics and osteogenic capability of stem cells derived from BFP as a valuable cell source for bone tissue engineering. An electronic search was performed on all in vitro and in vivo studies that used stem cells from BFP for the purpose of bone tissue engineering from 2010 until 2016. This review was organized according to the PRISMA statement. Adipose-derived stem cells derived from BFP (BFPSCs) were compared with adipose tissues from other parts of the body (AdSCs). Moreover, the osteogenic capability of dedifferentiated fat cells (DFAT) derived from BFP (BFP-DFAT) has been reported in comparison with BFPSCs. BFP is an easily accessible source of stem cells that can be obtained via the oral cavity without injury to the external body surface. Comparing BFPSCs with AdSCs indicated similar cell yield, morphology, and multilineage differentiation. However, BFPSCs proliferate faster and are more prone to producing colonies than AdSCs.
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Chirumbolo S, Bjørklund G. The sesquiterpene α-bisabolol in the adipocyte-cancer desmoplastic crosstalk: does it have an action on epithelial-mesenchymal transition mechanisms? Int J Clin Oncol 2017; 22:222-228. [PMID: 27942879 DOI: 10.1007/s10147-016-1072-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2016] [Accepted: 12/02/2016] [Indexed: 12/12/2022]
Abstract
Alpha-bisabolol is a plant-derived sesquiterpene alcohol recently associated with a supposed anti-cancer action due to its ability to induce BID-related apoptosis. The molecule, which enters the cell through lipid rafts, may also interact with kisspeptin receptor 1, which has recently been associated with tumor mobility and invasiveness. This evidence suggests the possibility that α-bisabolol might act on the epithelial-mesenchymal transition mechanism, closely associated with the desmoplastic reaction of adipose tissue surrounding a pancreatic ductal adenocarcinoma. This review addresses the issue on the basis of the most recent reported literature in the field.
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Affiliation(s)
- Salvatore Chirumbolo
- Department of Neurological and Movement Sciences, University of Verona, Strada Le Grazie 9, Verona, Italy.
- CONEM Scientific Secretary, Mo i Rana, Norway.
| | - Geir Bjørklund
- Council for Nutritional and Environmental Medicine, Mo i Rana, Norway
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Tsurumachi N, Akita D, Kano K, Matsumoto T, Toriumi T, Kazama T, Oki Y, Tamura Y, Tonogi M, Isokawa K, Shimizu N, Honda M. Small Buccal Fat Pad Cells Have High Osteogenic Differentiation Potential. Tissue Eng Part C Methods 2016; 22:250-9. [DOI: 10.1089/ten.tec.2015.0420] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Affiliation(s)
- Niina Tsurumachi
- Nihon University Graduate School of Dentistry, Chiyoda-ku, Japan
| | - Daisuke Akita
- Department of Partial Denture Prosthodontics, Nihon University School of Dentistry, Chiyoda-ku, Japan
| | - Koichiro Kano
- Laboratory of Cell and Tissue Biology, College of Bioresource Sciences, Nihon University, Fujisawa, Japan
| | - Taro Matsumoto
- Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Itabashi-ku, Japan
| | - Taku Toriumi
- Department of Anatomy, Nihon University School of Dentistry, Chiyoda-ku, Japan
| | - Tomohiko Kazama
- Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Itabashi-ku, Japan
| | - Yoshinao Oki
- Laboratory of Cell and Tissue Biology, College of Bioresource Sciences, Nihon University, Fujisawa, Japan
| | - Yoko Tamura
- Department of Orthodontics, Nihon University School of Dentistry, Chiyoda-ku, Japan
| | - Morio Tonogi
- Department of Oral Surgery, Nihon University School of Dentistry, Chiyoda-ku, Japan
| | - Keitaro Isokawa
- Department of Anatomy, Nihon University School of Dentistry, Chiyoda-ku, Japan
| | - Noriyoshi Shimizu
- Department of Orthodontics, Nihon University School of Dentistry, Chiyoda-ku, Japan
| | - Masaki Honda
- Department of Oral Anatomy, Aichi-Gakuin University School of Dentistry, Nagoya, Japan
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Jumabay M, Boström KI. Dedifferentiated fat cells: A cell source for regenerative medicine. World J Stem Cells 2015; 7:1202-1214. [PMID: 26640620 PMCID: PMC4663373 DOI: 10.4252/wjsc.v7.i10.1202] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Revised: 04/02/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
The identification of an ideal cell source for tissue regeneration remains a challenge in the stem cell field. The ability of progeny cells to differentiate into other cell types is important for the processes of tissue reconstruction and tissue engineering and has clinical, biochemical or molecular implications. The adaptation of stem cells from adipose tissue for use in regenerative medicine has created a new role for adipocytes. Mature adipocytes can easily be isolated from adipose cell suspensions and allowed to dedifferentiate into lipid-free multipotent cells, referred to as dedifferentiated fat (DFAT) cells. Compared to other adult stem cells, the DFAT cells have unique advantages in their abundance, ease of isolation and homogeneity. Under proper condition in vitro and in vivo, the DFAT cells have exhibited adipogenic, osteogenic, chondrogenic, cardiomyogenc, angiogenic, myogenic, and neurogenic potentials. In this review, we first discuss the phenomena of dedifferentiation and transdifferentiation of cells, and then dedifferentiation of adipocytes in particular. Understanding the dedifferentiation process itself may contribute to our knowledge of normal growth processes, as well as mechanisms of disease. Second, we highlight new developments in DFAT cell culture and summarize the current understanding of DFAT cell properties. The unique features of DFAT cells are promising for clinical applications such as tissue regeneration.
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15
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Guo B, Greenwood PL, Cafe LM, Zhou G, Zhang W, Dalrymple BP. Transcriptome analysis of cattle muscle identifies potential markers for skeletal muscle growth rate and major cell types. BMC Genomics 2015; 16:177. [PMID: 25887672 PMCID: PMC4364331 DOI: 10.1186/s12864-015-1403-x] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2014] [Accepted: 02/24/2015] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND This study aimed to identify markers for muscle growth rate and the different cellular contributors to cattle muscle and to link the muscle growth rate markers to specific cell types. RESULTS The expression of two groups of genes in the longissimus muscle (LM) of 48 Brahman steers of similar age, significantly enriched for "cell cycle" and "ECM (extracellular matrix) organization" Gene Ontology (GO) terms was correlated with average daily gain/kg liveweight (ADG/kg) of the animals. However, expression of the same genes was only partly related to growth rate across a time course of postnatal LM development in two cattle genotypes, Piedmontese x Hereford (high muscling) and Wagyu x Hereford (high marbling). The deposition of intramuscular fat (IMF) altered the relationship between the expression of these genes and growth rate. K-means clustering across the development time course with a large set of genes (5,596) with similar expression profiles to the ECM genes was undertaken. The locations in the clusters of published markers of different cell types in muscle were identified and used to link clusters of genes to the cell type most likely to be expressing them. Overall correspondence between published cell type expression of markers and predicted major cell types of expression in cattle LM was high. However, some exceptions were identified: expression of SOX8 previously attributed to muscle satellite cells was correlated with angiogenesis. Analysis of the clusters and cell types suggested that the "cell cycle" and "ECM" signals were from the fibro/adipogenic lineage. Significant contributions to these signals from the muscle satellite cells, angiogenic cells and adipocytes themselves were not as strongly supported. Based on the clusters and cell type markers, sets of five genes predicted to be representative of fibro/adipogenic precursors (FAPs) and endothelial cells, and/or ECM remodelling and angiogenesis were identified. CONCLUSIONS Gene sets and gene markers for the analysis of many of the major processes/cell populations contributing to muscle composition and growth have been proposed, enabling a consistent interpretation of gene expression datasets from cattle LM. The same gene sets are likely to be applicable in other cattle muscles and in other species.
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Affiliation(s)
- Bing Guo
- Key Laboratory of Meat Processing and Quality Control, Synergetic Innovation Centre of Food Safety and Nutrition, College of Food Science and Technology, Nanjing Agriculture University, Nanjing, 210095, P. R. China.
- CSIRO Agriculture Flagship, St. Lucia, QLD, 4067, Australia.
| | - Paul L Greenwood
- CSIRO Agriculture Flagship, Armidale, NSW, 2350, Australia.
- NSW Department of Primary Industries, University of New England, Armidale, NSW, 2351, Australia.
| | - Linda M Cafe
- NSW Department of Primary Industries, University of New England, Armidale, NSW, 2351, Australia.
| | - Guanghong Zhou
- Key Laboratory of Meat Processing and Quality Control, Synergetic Innovation Centre of Food Safety and Nutrition, College of Food Science and Technology, Nanjing Agriculture University, Nanjing, 210095, P. R. China.
| | - Wangang Zhang
- Key Laboratory of Meat Processing and Quality Control, Synergetic Innovation Centre of Food Safety and Nutrition, College of Food Science and Technology, Nanjing Agriculture University, Nanjing, 210095, P. R. China.
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16
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Lessard J, Côté JA, Lapointe M, Pelletier M, Nadeau M, Marceau S, Biertho L, Tchernof A. Generation of human adipose stem cells through dedifferentiation of mature adipocytes in ceiling cultures. J Vis Exp 2015:52485. [PMID: 25867041 PMCID: PMC4401230 DOI: 10.3791/52485] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Mature adipocytes have been shown to reverse their phenotype into fibroblast-like cells in vitro through a technique called ceiling culture. Mature adipocytes can also be isolated from fresh adipose tissue for depot-specific characterization of their function and metabolic properties. Here, we describe a well-established protocol to isolate mature adipocytes from adipose tissues using collagenase digestion, and subsequent steps to perform ceiling cultures. Briefly, adipose tissues are incubated in a Krebs-Ringer-Henseleit buffer containing collagenase to disrupt tissue matrix. Floating mature adipocytes are collected on the top surface of the buffer. Mature cells are plated in a T25-flask completely filled with media and incubated upside down for a week. An alternative 6-well plate culture approach allows the characterization of adipocytes undergoing dedifferentiation. Adipocyte morphology drastically changes over time of culture. Immunofluorescence can be easily performed on slides cultivated in 6-well plates as demonstrated by FABP4 immunofluorescence staining. FABP4 protein is present in mature adipocytes but down-regulated through dedifferentiation of fat cells. Mature adipocyte dedifferentiation may represent a new avenue for cell therapy and tissue engineering.
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Affiliation(s)
| | | | | | | | | | | | | | - André Tchernof
- IUCPQ Research Center; CHU de Québec Research Center; Laval University;
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17
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Kaku M, Akiba Y, Akiyama K, Akita D, Nishimura M. Cell-based bone regeneration for alveolar ridge augmentation--cell source, endogenous cell recruitment and immunomodulatory function. J Prosthodont Res 2015; 59:96-112. [PMID: 25749435 DOI: 10.1016/j.jpor.2015.02.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Accepted: 02/05/2015] [Indexed: 11/30/2022]
Abstract
Alveolar ridge plays a pivotal role in supporting dental prosthesis particularly in edentulous and semi-dentulous patients. However the alveolar ridge undergoes atrophic change after tooth loss. The vertical and horizontal volume of the alveolar ridge restricts the design of dental prosthesis; thus, maintaining sufficient alveolar ridge volume is vital for successful oral rehabilitation. Recent progress in regenerative approaches has conferred marked benefits in prosthetic dentistry, enabling regeneration of the atrophic alveolar ridge. In order to achieve successful alveolar ridge augmentation, sufficient numbers of osteogenic cells are necessary; therefore, autologous osteoprogenitor cells are isolated, expanded in vitro, and transplanted to the specific anatomical site where the bone is required. Recent studies have gradually elucidated that transplanted osteoprogenitor cells are not only a source of bone forming osteoblasts, they appear to play multiple roles, such as recruitment of endogenous osteoprogenitor cells and immunomodulatory function, at the forefront of bone regeneration. This review focuses on the current consensus of cell-based bone augmentation therapies with emphasis on cell sources, transplanted cell survival, endogenous stem cell recruitment and immunomodulatory function of transplanted osteoprogenitor cells. Furthermore, if we were able to control the mobilization of endogenous osteoprogenitor cells, large-scale surgery may no longer be necessary. Such treatment strategy may open a new era of safer and more effective alveolar ridge augmentation treatment options.
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Affiliation(s)
- Masaru Kaku
- Division of Bioprosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Yosuke Akiba
- Division of Bioprosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Kentaro Akiyama
- Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Daisuke Akita
- Department of Partial Denture Prosthodontics, Nihon University School of Dentistry, Tokyo, Japan
| | - Masahiro Nishimura
- Department of Oral Maxillofacial Prosthodontics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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Song N, Kou L, Lu XW, Sugawara A, Shimizu Y, Wu MK, Du L, Wang H, Sato S, Shen JF. The perivascular phenotype and behaviors of dedifferentiated cells derived from human mature adipocytes. Biochem Biophys Res Commun 2015; 457:479-84. [DOI: 10.1016/j.bbrc.2015.01.033] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2014] [Accepted: 01/10/2015] [Indexed: 01/29/2023]
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