|
1
|
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.
Collapse
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.
| |
Collapse
|
|
2
|
Kamidaki Y, Hosokawa T, Abe N, Fujita E, Yamaoka B, Ono K, Goto S, Kazama T, Matsumoto T, Uehara S. Muscle regeneration therapy using dedifferentiated fat cell (DFAT) for anal sphincter dysfunction. Pediatr Surg Int 2024; 40:238. [PMID: 39167102 DOI: 10.1007/s00383-024-05812-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/07/2024] [Indexed: 08/23/2024]
Abstract
PURPOSE We investigated the effects of mouse-derived DFAT on the myogenic differentiation of a mouse-derived myoblast cell line (C2C12) and examined the therapeutic effects of rat-derived DFAT on anal sphincter injury using a rat model. METHODS C2C12 cells were cultured using DMEM and DFAT-conditioned medium (DFAT-CM), evaluating MyoD and Myogenin gene expression via RT-PCR. DFAT was locally administered to model rats with anorectal sphincter dysfunction 3 days post-CTX injection. Therapeutic effects were assessed through functional assessment, including anal pressure measurement using solid-state manometry pre/post-CTX, and on days 1, 3, 7, 10, 14, 17, and 21 post-DFAT administration. Histological evaluation involved anal canal excision on days 1, 3, 7, 14, and 21 after CTX administration, followed by hematoxylin-eosin staining. RESULTS C2C12 cells cultured with DFAT-CM exhibited increased MyoD and Myogenin gene expression compared to control. Anal pressure measurements revealed early recovery of resting pressure in the DFAT-treated group. Histologically, DFAT-treated rats demonstrated an increase in mature muscle cells within newly formed muscle fibers on days 14 and 21 after CTX administration, indicating enhanced muscle tissue repair. CONCLUSION DFAT demonstrated the potential to enhance histological and functional muscle tissue repair. These findings propose DFAT as a novel therapeutic approach for anorectal sphincter dysfunction treatment.
Collapse
Affiliation(s)
- Yusuke Kamidaki
- Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Takashi Hosokawa
- Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Naoko Abe
- Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Eri Fujita
- Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Bin Yamaoka
- Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Kako Ono
- Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Shumpei Goto
- Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Tomohiko Kazama
- Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan
| | - Taro Matsumoto
- Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan
| | - Shuichiro Uehara
- Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan.
| |
Collapse
|
|
3
|
Karanfil AS, Louis F, Sowa Y, Matsusaki M. Cationic polymer effect on brown adipogenic induction of dedifferentiated fat cells. Mater Today Bio 2024; 27:101157. [PMID: 39113911 PMCID: PMC11304885 DOI: 10.1016/j.mtbio.2024.101157] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 07/12/2024] [Accepted: 07/12/2024] [Indexed: 08/10/2024] Open
Abstract
Obesity and its associated comorbidities place a substantial burden on public health. Given the considerable potential of brown adipose tissue in addressing metabolic disorders that contribute to dysregulation of the body's energy balance, this area is an intriguing avenue for research. This study aimed to assess the impact of various polymers, including collagen type I, fibronectin, laminin, gelatin, gellan gum, and poly-l-lysine (PLL), on the in vitro brown adipogenic differentiation of dedifferentiated fat cells within a fibrin gel matrix. The findings, obtained through RT-qPCR, immunofluorescent imaging, ELISA assay, and mitochondria assessment, revealed that PLL exhibited a significant browning-inducing effect. Compared to fibrin-only brown-like drops after two weeks of incubation in brown adipogenic medium, PLL showed 6 (±3) times higher UCP1 gene expression, 5 (±2) times higher UCP1 concentration by ELISA assay, and 2 (±1) times higher mitochondrial content. This effect can be attributed to PLL's electrostatic properties, which potentially facilitate the cellular uptake of crucial brown adipogenic inducers such as the thyroid hormone, triiodothyronine (T3), and insulin from the induction medium.
Collapse
Affiliation(s)
- Aslı Sena Karanfil
- Department of Applied Chemistry, Graduate School of Osaka University, Japan
| | - Fiona Louis
- Joint Research Laboratory (TOPPAN) for Advanced Cell Regulatory Chemistry, Graduate School of Osaka University, Japan
| | - Yoshihiro Sowa
- Department of Plastic Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
- Department of Plastic and Reconstructive Surgery, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Japan
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Japan
| | - Michiya Matsusaki
- Department of Applied Chemistry, Graduate School of Osaka University, Japan
- Joint Research Laboratory (TOPPAN) for Advanced Cell Regulatory Chemistry, Graduate School of Osaka University, Japan
| |
Collapse
|
|
4
|
Ishizawa M, Takano M, Kittaka A, Matsumoto T, Makishima M. 2α-Substituted Vitamin D Derivatives Effectively Enhance the Osteoblast Differentiation of Dedifferentiated Fat Cells. Biomolecules 2024; 14:706. [PMID: 38927109 PMCID: PMC11202298 DOI: 10.3390/biom14060706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 06/08/2024] [Accepted: 06/13/2024] [Indexed: 06/28/2024] Open
Abstract
The active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], is a principal regulator of calcium homeostasis through activation of the vitamin D receptor (VDR). Previous studies have shown that 2α-(3-hydroxypropyl)-1,25D3 (O1C3) and 2α-(3-hydroxypropoxy)-1,25D3 (O2C3), vitamin D derivatives resistant to inactivation enzymes, can activate VDR, induce leukemic cell differentiation, and increase blood calcium levels in rats more effectively than 1,25(OH)2D3. In this study, to further investigate the usefulness of 2α-substituted vitamin D derivatives, we examined the effects of O2C3, O1C3, and their derivatives on VDR activity in cells and mouse tissues and on osteoblast differentiation of dedifferentiated fat (DFAT) cells, a cell type with potential therapeutic application in regenerative medicine. In cell culture experiments using kidney-derived HEK293 cells, intestinal mucosa-derived CaCO2 cells, and osteoblast-derived MG63 cells, and in mouse experiments, O2C2, O2C3, O1C3, and O1C4 had a weaker effect than or equivalent effect to 1,25(OH)2D3 in VDR transactivation and induction of the VDR target gene CYP24A1, but they enhanced osteoblast differentiation in DFAT cells equally to or more effectively than 1,25(OH)2D3. In long-term treatment with the compound without the medium change (7 days), the derivatives enhanced osteoblast differentiation more effectively than 1,25(OH)2D3. O2C3 and O1C3 were more stable than 1,25(OH)2D3 in DFAT cell culture. These results indicate that 2α-substituted vitamin D derivatives, such as inactivation-resistant O2C3 and O1C3, are more effective than 1,25(OH)2D3 in osteoblast differentiation of DFAT cells, suggesting potential roles in regenerative medicine with DFAT cells and other multipotent cells.
Collapse
Affiliation(s)
- Michiyasu Ishizawa
- Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Masashi Takano
- Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan; (M.T.); (A.K.)
| | - Atsushi Kittaka
- Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan; (M.T.); (A.K.)
| | - Taro Matsumoto
- Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Tokyo 173-8610, Japan;
| | - Makoto Makishima
- Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| |
Collapse
|
|
5
|
Longo B, D'Orsi G, Farcomeni A, Pistoia A, Giacalone M, Gagliano E, Vannucchi L, Vanni G, Buonomo CO, Cervelli V. The FALD-V: A predictive formula for preoperative volume assessment of adipose tissue transplantation in FALD flap. J Plast Reconstr Aesthet Surg 2024; 90:25-34. [PMID: 38340688 DOI: 10.1016/j.bjps.2024.01.014] [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: 10/11/2023] [Revised: 12/08/2023] [Accepted: 01/29/2024] [Indexed: 02/12/2024]
Abstract
BACKGROUND The fat-augmented latissimus dorsi (FALD) flap is an evolution of the traditional latissimus dorsi (LD) flap, which allows to obtain a total autologous breast reconstruction (BR) avoiding the use of breast implants. The aim of this study was to develop a predictive preoperative formula in order to estimate and optimize the amount of fat to be transferred during FALD flap BR, using only anthropometric measurements. METHODS We conducted a prospective clinical study between September 2020 and April 2023. All patients underwent back pre-operative ultrasound scan to assess the subcutaneous skin paddle thickness (SPT) and a regression analysis was performed to evaluate which anthropometric variable had a better correlation with this thickness. RESULTS Data from 66 FALD flaps were collected. The mean SPT was 11.95 mm (SD 4.56). A significant correlation between SPT and body mass index (BMI) was found (r = 0.640, p < 0.0001). Using the fat-to-capacity ratio (113%), the following formula (the FALD-V) was developed to predict the needed fat transfer into FALD flap: [-509 + 12.32 × BMI + 11.71 × skin paddle width + 17.43 × skin paddle height] × 1.13. The considered variables (BMI, skin paddle width and skin paddle height) were statistically significant (p < 0.001, p = 0.0483, p = 0.0154, respectively). The cross-validation confirmed the accuracy of the formula (r = 0.810). CONCLUSION The FALD-V can be used as an innovative complimentary device in the planning of FALD flap one-stage total autologous BR. To enhance its application, a 3.0 WebApp at www.braflap.com (and www.breast-v.com) is available free of charge for both iOS and Android devices. LEVEL OF EVIDENCE II.
Collapse
Affiliation(s)
- Benedetto Longo
- Department of Surgical Sciences, School of Medicine and Surgery, Tor Vergata University of Rome, Rome, Italy.
| | - Gennaro D'Orsi
- PhD School of Applied Medical-Surgical Sciences,University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
| | - Alessio Farcomeni
- Department of Economics & Finance, Tor Vergata University of Rome, Rome, Italy
| | - Angelica Pistoia
- Department of Surgical Sciences, School of Medicine and Surgery, Tor Vergata University of Rome, Rome, Italy
| | - Martina Giacalone
- Department of Surgical Sciences, School of Medicine and Surgery, Tor Vergata University of Rome, Rome, Italy
| | - Elettra Gagliano
- Department of Surgical Sciences, School of Medicine and Surgery, Tor Vergata University of Rome, Rome, Italy
| | - Lisa Vannucchi
- Department of Surgical Sciences, School of Medicine and Surgery, Tor Vergata University of Rome, Rome, Italy
| | - Gianluca Vanni
- Division of Breast Unit, Department of Surgical Sciences, School of Medicine and Surgery, Tor Vergata University of Rome, Rome, Italy
| | - Claudio Oreste Buonomo
- Division of Breast Unit, Department of Surgical Sciences, School of Medicine and Surgery, Tor Vergata University of Rome, Rome, Italy
| | - Valerio Cervelli
- Department of Surgical Sciences, School of Medicine and Surgery, Tor Vergata University of Rome, Rome, Italy
| |
Collapse
|
|
6
|
Karanfil AS, Louis F, Sowa Y, Matsusaki M. ECM proteins and cationic polymers coating promote dedifferentiation of patient-derived mature adipocytes to stem cells. Biomater Sci 2023; 11:7623-7638. [PMID: 37830400 DOI: 10.1039/d3bm00934c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2023]
Abstract
Reprogramming of mature adipocytes is an attractive research area due to the plasticity of these cells. Mature adipocytes can be reprogrammed in vitro, transforming them into dedifferentiated fat cells (DFATs), which are considered a new type of stem cell, and thereby have a high potential for use in tissue engineering and regenerative medicine. However, there are still no reports or findings on in vitro controlling the dedifferentiation. Although ceiling culture performed in related studies is a relatively simple method, its yield is low and does not allow manipulation of mature adipocytes to increase or decrease the dedifferentiation. In this study, to understand the role of physicochemical surface effects on the dedifferentiation of patient-derived mature adipocytes, the surfaces of cell culture flasks were coated with extracellular matrix, basement membrane proteins, and cationic/anionic polymers. Extracellular matrix such as fibronectin and collagen type I, and basement membrane proteins such as collagen type IV and laminin strongly promoted dedifferentiation of mature adipocytes, with laminin showing the highest effect with a DFAT ratio of 2.98 (±0.84). Interestingly, cationic polymers also showed a high dedifferentiation effect, but anionic polymers did not, and poly(diallyl dimethylammonium chloride) showed the highest DFAT ratio of 2.27 (±2.8) among the cationic polymers. Protein assay results revealed that serum proteins were strongly adsorbed on the surfaces of the cationic polymer coating, including inducing high mature adipocyte adhesion. This study demonstrates for the first time the possibility of regulating the transformation of mature adipocytes to DFAT stem cells by controlling the physicochemical properties of the surface of conventional cell culture flasks.
Collapse
Affiliation(s)
- Aslı Sena Karanfil
- Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Japan.
| | - Fiona Louis
- Joint Research Laboratory (TOPPAN) for Advanced Cell Regulatory Chemistry, Graduate School of Engineering, Osaka University, Japan
| | - Yoshihiro Sowa
- Department of Plastic and Reconstructive Surgery, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Japan
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Japan
| | - Michiya Matsusaki
- Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Japan.
- Joint Research Laboratory (TOPPAN) for Advanced Cell Regulatory Chemistry, Graduate School of Engineering, Osaka University, Japan
| |
Collapse
|
|
7
|
Kulus M, Jankowski M, Kranc W, Golkar Narenji A, Farzaneh M, Dzięgiel P, Zabel M, Antosik P, Bukowska D, Mozdziak P, Kempisty B. Bioreactors, scaffolds and microcarriers and in vitro meat production-current obstacles and potential solutions. Front Nutr 2023; 10:1225233. [PMID: 37743926 PMCID: PMC10513094 DOI: 10.3389/fnut.2023.1225233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 08/21/2023] [Indexed: 09/26/2023] Open
Abstract
In vitro meat production presents a potential viable alternative for meat consumption, which could provide the consumer with a product indistinguishable from the original, with very similar nutritional and culinary values. Indeed, the alternative products currently accessible often lack comparable nutritional value or culinary attributes to their animal-derived counterparts. This creates challenges for their global acceptance, particularly in countries where meat consumption holds cultural significance. However, while cultured meat research has been progressing rapidly in recent years, some significant obstacles still need to be overcome before its possible commercialization. Hence, this review summarizes the most current knowledge regarding the history of cultured meat, the currently used cell sources and methods used for the purpose of in vitro meat production, with particular focus on the role of bioreactors, scaffolds and microcarriers in overcoming the current obstacles. The authors put the potential microcarrier and scaffold-based solutions in a context, discussing the ways in which they can impact the way forward for the technology, including the use of considering the potential practical and societal barriers to implementing it as a viable food source worldwide.
Collapse
Affiliation(s)
- Magdalena Kulus
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Toruń, Toruń, Poland
| | - Maurycy Jankowski
- Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznan, Poland
- Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan, Poland
| | - Wiesława Kranc
- Department of Anatomy, Poznan University of Medical Sciences, Poznań, Poland
| | - Afsaneh Golkar Narenji
- Prestage Department of Poultry Science, North Carolina State University, Raleigh, NC, United States
| | - Maryam Farzaneh
- Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Piotr Dzięgiel
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, Wroclaw, Poland
| | - Maciej Zabel
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, Wroclaw, Poland
- Division of Anatomy and Histology, University of Zielona Góra, Zielona Góra, Poland
| | - Paweł Antosik
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Toruń, Toruń, Poland
| | - Dorota Bukowska
- Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Toruń, Toruń, Poland
| | - Paul Mozdziak
- Prestage Department of Poultry Science, North Carolina State University, Raleigh, NC, United States
- Physiology Graduate Faculty, North Carolina State University, Raleigh, NC, United States
| | - Bartosz Kempisty
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Toruń, Toruń, Poland
- Physiology Graduate Faculty, North Carolina State University, Raleigh, NC, United States
- Division of Anatomy, Department of Human Morphology and Embryology, Wroclaw Medical University, Wroclaw, Poland
- Department of Obstetrics and Gynecology, University Hospital and Masaryk University, Brno, Czechia
| |
Collapse
|
|
8
|
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.
Collapse
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.
| |
Collapse
|
|
9
|
Mimatsu H, Onoda A, Kazama T, Nishijima K, Shimoyama Y, Go S, Ueda K, Takahashi Y, Matsumoto T, Hayakawa M, Sato Y. Dedifferentiated fat cells administration ameliorates abnormal expressions of fatty acids metabolism-related protein expressions and intestinal tissue damage in experimental necrotizing enterocolitis. Sci Rep 2023; 13:8266. [PMID: 37217485 DOI: 10.1038/s41598-023-34156-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 04/25/2023] [Indexed: 05/24/2023] Open
Abstract
Neonatal necrotizing enterocolitis (NEC) is a serious disease of premature infants that necessitates intensive care and frequently results in life-threatening complications and high mortality. Dedifferentiated fat cells (DFATs) are mesenchymal stem cell-like cells derived from mature adipocytes. DFATs were intraperitoneally administrated to a rat NEC model, and the treatment effect and its mechanism were evaluated. The NEC model was created using rat pups hand fed with artificial milk, exposed to asphyxia and cold stress, and given oral lipopolysaccharides after cesarean section. The pups were sacrificed 96 h after birth for macroscopic histological examination and proteomics analysis. DFATs administration significantly improved the survival rate from 25.0 (vehicle group) to 60.6% (DFAT group) and revealed a significant reduction in macroscopical, histological, and apoptosis evaluation compared with the vehicle group. Additionally, the expression of C-C motif ligand 2 was significantly decreased, and that of interleukin-6 decreased in the DFAT group. DFAT administration ameliorated 93 proteins mainly related to proteins of fatty acid metabolism of the 436 proteins up-/down-regulated by NEC. DFATs improved mortality and restored damaged intestinal tissues in NEC, possibly by improving the abnormal expression of fatty acid-related proteins and reducing inflammation.
Collapse
Affiliation(s)
- Haruka Mimatsu
- Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, 65 Tsurumai-Cho Showa-Ku, Nagoya, 466-8550, Japan
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Atsuto Onoda
- Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, 65 Tsurumai-Cho Showa-Ku, Nagoya, 466-8550, Japan
- Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo-Onoda, Yamaguchi, Japan
| | - Tomohiko Kazama
- Department of Functional Morphology, Division of Cell Regeneration and Transplantation, Nihon University School of Medicine, Tokyo, Japan
| | - Koji Nishijima
- Center for Perinatal, Maternal and Neonatal Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - Yoshie Shimoyama
- Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shoji Go
- Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, 65 Tsurumai-Cho Showa-Ku, Nagoya, 466-8550, Japan
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kazuto Ueda
- Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, 65 Tsurumai-Cho Showa-Ku, Nagoya, 466-8550, Japan
| | - Yoshiyuki Takahashi
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Taro Matsumoto
- Department of Functional Morphology, Division of Cell Regeneration and Transplantation, Nihon University School of Medicine, Tokyo, Japan
| | - Masahiro Hayakawa
- Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, 65 Tsurumai-Cho Showa-Ku, Nagoya, 466-8550, Japan
| | - Yoshiaki Sato
- Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, 65 Tsurumai-Cho Showa-Ku, Nagoya, 466-8550, Japan.
| |
Collapse
|
|
10
|
Santanelli di Pompeo F, D'Orsi G, Firmani G, Paolini G, Renzi LF, Sorotos M. Total breast reconstruction with the fat-augmented latissimus dorsi (FALD) flap: High safety in a single-center uncontrolled case series. J Plast Reconstr Aesthet Surg 2022; 75:3004-3013. [PMID: 35907690 DOI: 10.1016/j.bjps.2022.06.052] [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: 03/06/2021] [Revised: 04/25/2022] [Accepted: 06/10/2022] [Indexed: 10/18/2022]
Abstract
According to ASPS, 107,238 breast reconstructions (BR) have been performed in the United States this year. The latissimus dorsi (LD) flap is used for breast reconstruction (BR), either with an implant or an extended flap harvest. Implant-enhanced LD is associated with 50% reoperation rates. To avoid implant-related complications, we introduced the Fat-Augmented LD (FALD) flap. Several authors report 92% patient satisfaction and 36% complication rates (CR). The aim of our study is to present a single-center uncontrolled case series with long follow-up assessing CR and esthetic results. Women with small-to-moderate breasts requiring immediate or delayed BR were included, whereas athletic and paraplegic women or patients with contraindication for free flap BR were excluded. Clinical and surgical data were analyzed. Esthetic analysis was performed using a panel of independent observers. Between December 2010 and November 2019, 100 patients underwent 148 FALD-based BR. Average operative time was 193.5 min for unilateral procedure and 290.6 min for bilateral procedure. Mean immediate AFT volume was 105.3 cc (range 60-170) per breast. Major complication (total or partial flap necrosis > 30%) rate was 0%, and minor complication (partial flap necrosis < 30%, fat necrosis hematoma, seroma, donor site dehiscence, and chronic pain) rate was 6.76%. Esthetic analysis garnered satisfactory results for all types of mastectomies. For variables regarding skin texture (p = 0.001), scar location (p = 0.005), and total score (p = 0.001), patients undergoing Modified Radical Mastectomy scored lower than Skin-Sparing Mastectomy and Nipple-Sparing Mastectomy. We were able to confirm that the FALD flap is a safe with a low complication rate and high patient satisfaction. Level of Evidence IV.
Collapse
Affiliation(s)
- Fabio Santanelli di Pompeo
- Chair of Plastic Surgery, Faculty of Medicine and Psychology, Sapienza University of Rome - Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy.
| | - Gennaro D'Orsi
- Faculty of Medicine and Psychology, Sapienza University of Rome - Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy
| | - Guido Firmani
- Faculty of Medicine and Psychology, Sapienza University of Rome - Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy
| | - Guido Paolini
- Faculty of Medicine and Psychology, Sapienza University of Rome - Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy
| | - Luca Francesco Renzi
- Plastic Surgery Department, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy
| | - Michail Sorotos
- Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", PhD School of Translational Medicine of Development and Active Ageing, Università degli Studi di Salerno, Salerno, Italy
| |
Collapse
|
|
11
|
Abstract
In vitro meat (IVM) is a recent development in the production of sustainable food. The consumer perception of IVM has a strong impact on the commercial success of IVM. Hence this review examines existing studies related to consumer concerns, acceptance and uncertainty of IVM. This will help create better marketing strategies for IVM-producing companies in the future. In addition, IVM production is described in terms of the types of cells and culture conditions employed. The applications of self-organising, scaffolding, and 3D printing techniques to produce IVM are also discussed. As the conditions for IVM production are controlled and can be manipulated, it will be feasible to produce a chemically safe and disease-free meat with improved consumer acceptance on a sustainable basis.
Collapse
|
|
12
|
Transplantation of Mature Adipocyte-Derived Dedifferentiated Fat Cells Facilitates Periodontal Tissue Regeneration of Class II Furcation Defects in Miniature Pigs. MATERIALS 2022; 15:ma15041311. [PMID: 35207844 PMCID: PMC8875781 DOI: 10.3390/ma15041311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/27/2022] [Accepted: 02/06/2022] [Indexed: 12/10/2022]
Abstract
Adipose tissue is composed mostly of adipocytes that are in contact with capillaries. By using a ceiling culture method based on buoyancy, lipid-free fibroblast-like cells, also known as dedifferentiated fat (DFAT) cells, can be separated from mature adipocytes with a large single lipid droplet. DFAT cells can re-establish their active proliferation ability and transdifferentiate into various cell types under appropriate culture conditions. Herein, we sought to compare the regenerative potential of collagen matrix alone (control) with autologous DFAT cell-loaded collagen matrix transplantation in adult miniature pigs (microminipigs; MMPs). We established and transplanted DFAT cells into inflammation-inducing periodontal class II furcation defects. At 12 weeks after cell transplantation, a marked attachment gain was observed based on the clinical parameters of probing depth (PD) and clinical attachment level (CAL). Additionally, micro computed tomography (CT) revealed hard tissue formation in furcation defects of the second premolar. The cemento-enamel junction and alveolar bone crest distance was significantly shorter following transplantation. Moreover, newly formed cellular cementum, well-oriented periodontal ligament-like fibers, and alveolar bone formation were observed via histological analysis. No teratomas were found in the internal organs of recipient MMPs. Taken together, these findings suggest that DFAT cells can safely enhance periodontal tissue regeneration.
Collapse
|
|
13
|
Yuen JSK, Stout AJ, Kawecki NS, Letcher SM, Theodossiou SK, Cohen JM, Barrick BM, Saad MK, Rubio NR, Pietropinto JA, DiCindio H, Zhang SW, Rowat AC, Kaplan DL. Perspectives on scaling production of adipose tissue for food applications. Biomaterials 2022; 280:121273. [PMID: 34933254 PMCID: PMC8725203 DOI: 10.1016/j.biomaterials.2021.121273] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 11/22/2021] [Accepted: 11/23/2021] [Indexed: 01/03/2023]
Abstract
With rising global demand for food proteins and significant environmental impact associated with conventional animal agriculture, it is important to develop sustainable alternatives to supplement existing meat production. Since fat is an important contributor to meat flavor, recapitulating this component in meat alternatives such as plant based and cell cultured meats is important. Here, we discuss the topic of cell cultured or tissue engineered fat, growing adipocytes in vitro that could imbue meat alternatives with the complex flavor and aromas of animal meat. We outline potential paths for the large scale production of in vitro cultured fat, including adipogenic precursors during cell proliferation, methods to adipogenically differentiate cells at scale, as well as strategies for converting differentiated adipocytes into 3D cultured fat tissues. We showcase the maturation of knowledge and technology behind cell sourcing and scaled proliferation, while also highlighting that adipogenic differentiation and 3D adipose tissue formation at scale need further research. We also provide some potential solutions for achieving adipose cell differentiation and tissue formation at scale based on contemporary research and the state of the field.
Collapse
Affiliation(s)
- John S K Yuen
- Biomedical Engineering Department, Tissue Engineering Resource Center, Tufts University, 4 Colby St, Medford, MA, 02155, USA
| | - Andrew J Stout
- Biomedical Engineering Department, Tissue Engineering Resource Center, Tufts University, 4 Colby St, Medford, MA, 02155, USA
| | - N Stephanie Kawecki
- Department of Bioengineering, University of California Los Angeles, 410 Westwood Plaza, Los Angeles, CA, 90095, USA; Department of Integrative Biology & Physiology, University of California Los Angeles, Terasaki Life Sciences Building, 610 Charles E. Young Drive South, Los Angeles, CA, 90095, USA
| | - Sophia M Letcher
- Biomedical Engineering Department, Tissue Engineering Resource Center, Tufts University, 4 Colby St, Medford, MA, 02155, USA
| | - Sophia K Theodossiou
- Biomedical Engineering Department, Tissue Engineering Resource Center, Tufts University, 4 Colby St, Medford, MA, 02155, USA
| | - Julian M Cohen
- W. M. Keck Science Department, Pitzer College, 925 N Mills Ave, Claremont, CA, 91711, USA
| | - Brigid M Barrick
- Biomedical Engineering Department, Tissue Engineering Resource Center, Tufts University, 4 Colby St, Medford, MA, 02155, USA
| | - Michael K Saad
- Biomedical Engineering Department, Tissue Engineering Resource Center, Tufts University, 4 Colby St, Medford, MA, 02155, USA
| | - Natalie R Rubio
- Biomedical Engineering Department, Tissue Engineering Resource Center, Tufts University, 4 Colby St, Medford, MA, 02155, USA
| | - Jaymie A Pietropinto
- Biomedical Engineering Department, Tissue Engineering Resource Center, Tufts University, 4 Colby St, Medford, MA, 02155, USA
| | - Hailey DiCindio
- Biomedical Engineering Department, Tissue Engineering Resource Center, Tufts University, 4 Colby St, Medford, MA, 02155, USA
| | - Sabrina W Zhang
- Biomedical Engineering Department, Tissue Engineering Resource Center, Tufts University, 4 Colby St, Medford, MA, 02155, USA
| | - Amy C Rowat
- Department of Bioengineering, University of California Los Angeles, 410 Westwood Plaza, Los Angeles, CA, 90095, USA; Department of Integrative Biology & Physiology, University of California Los Angeles, Terasaki Life Sciences Building, 610 Charles E. Young Drive South, Los Angeles, CA, 90095, USA
| | - David L Kaplan
- Biomedical Engineering Department, Tissue Engineering Resource Center, Tufts University, 4 Colby St, Medford, MA, 02155, USA.
| |
Collapse
|
|
14
|
Takabatake K, Matsubara M, Yamachika E, Fujita Y, Arimura Y, Nakatsuji K, Nakano K, Nagatsuka H, Iida S. Comparing the Osteogenic Potential and Bone Regeneration Capacities of Dedifferentiated Fat Cells and Adipose-Derived Stem Cells In Vitro and In Vivo: Application of DFAT Cells Isolated by a Mesh Method. Int J Mol Sci 2021; 22:12392. [PMID: 34830277 PMCID: PMC8620969 DOI: 10.3390/ijms222212392] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/14/2021] [Accepted: 11/16/2021] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND We investigated and compared the osteogenic potential and bone regeneration capacities of dedifferentiated fat cells (DFAT cells) and adipose-derived stem cells (ASCs). METHOD We isolated DFAT cells and ASCs from GFP mice. DFAT cells were established by a new culture method using a mesh culture instead of a ceiling culture. The isolated DFAT cells and ASCs were incubated in osteogenic medium, then alizarin red staining, alkaline phosphatase (ALP) assays, and RT-PCR (for RUNX2, osteopontin, DLX5, osterix, and osteocalcin) were performed to evaluate the osteoblastic differentiation ability of both cell types in vitro. In vivo, the DFAT cells and ASCs were incubated in osteogenic medium for four weeks and seeded on collagen composite scaffolds, then implanted subcutaneously into the backs of mice. We then performed hematoxylin and eosin staining and immunostaining for GFP and osteocalcin. RESULTS The alizarin red-stained areas in DFAT cells showed weak calcification ability at two weeks, but high calcification ability at three weeks, similar to ASCs. The ALP levels of ASCs increased earlier than in DFAT cells and showed a significant difference (p < 0.05) at 6 and 9 days. The ALP levels of DFATs were higher than those of ASCs after 12 days. The expression levels of osteoblast marker genes (osterix and osteocalcin) of DFAT cells and ASCs were higher after osteogenic differentiation culture. CONCLUSION DFAT cells are easily isolated from a small amount of adipose tissue and are readily expanded with high purity; thus, DFAT cells are applicable to many tissue-engineering strategies and cell-based therapies.
Collapse
Affiliation(s)
- Kiyofumi Takabatake
- Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (K.T.); (K.N.); (H.N.)
| | - Masakazu Matsubara
- Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (Y.A.); (K.N.); (S.I.)
| | - Eiki Yamachika
- Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (Y.A.); (K.N.); (S.I.)
- Department of Dentistry, National Hospital Organization Okayama Medical Center, Okayama 701-1192, Japan
| | - Yuki Fujita
- Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Hospital, Okayama 700-8525, Japan;
| | - Yuki Arimura
- Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (Y.A.); (K.N.); (S.I.)
| | - Kazuki Nakatsuji
- Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (Y.A.); (K.N.); (S.I.)
| | - Keisuke Nakano
- Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (K.T.); (K.N.); (H.N.)
| | - Histoshi Nagatsuka
- Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (K.T.); (K.N.); (H.N.)
| | - Seiji Iida
- Department of Oral and Maxillofacial Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan; (Y.A.); (K.N.); (S.I.)
- Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Hospital, Okayama 700-8525, Japan;
| |
Collapse
|
|
15
|
Liu L, Liu M, Xie D, Liu X, Yan H. Role of the extracellular matrix and YAP/TAZ in cell reprogramming. Differentiation 2021; 122:1-6. [PMID: 34768156 DOI: 10.1016/j.diff.2021.11.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 10/25/2021] [Accepted: 11/01/2021] [Indexed: 01/04/2023]
Abstract
Stem cells are crucial in the fields of regenerative medicine and cell therapy. Mechanical signals from the cellular microenvironment play an important role in inducing the reprogramming of somatic cells into stem cells in vitro, but the mechanisms of this process have yet to be fully explored. Mechanical signals may activate a physical pathway involving the focal adhesions-cytoskeleton-LINC complex axis, and a chemical pathway involving YAP/TAZ. ENH protein likely plays an important role in connecting and regulating these two pathways. Such mechanisms illustrate one way in which mechanical signals from the cellular microenvironment can induce reprogramming of somatic cells to stem cells, and lays the foundation for a new strategy for inducing and regulating such reprogramming in vitro by means of physical processes related to local mechanical forces.
Collapse
Affiliation(s)
- Lan Liu
- Department of Plastic and Burns Surgery, The Affiliated Hospital of Southwest Medical University, National Key Clinical Construction Specialty, Wound Repair and Regeneration Laboratory, Luzhou, Sichuan Province, 646000, China
| | - Mengchang Liu
- Department of Plastic and Burns Surgery, The Affiliated Hospital of Southwest Medical University, National Key Clinical Construction Specialty, Wound Repair and Regeneration Laboratory, Luzhou, Sichuan Province, 646000, China
| | - Defu Xie
- Department of Plastic and Burns Surgery, The Affiliated Hospital of Southwest Medical University, National Key Clinical Construction Specialty, Wound Repair and Regeneration Laboratory, Luzhou, Sichuan Province, 646000, China
| | - Xingke Liu
- Department of Plastic and Burns Surgery, The Affiliated Hospital of Southwest Medical University, National Key Clinical Construction Specialty, Wound Repair and Regeneration Laboratory, Luzhou, Sichuan Province, 646000, China
| | - Hong Yan
- Department of Plastic and Burns Surgery, The Affiliated Hospital of Southwest Medical University, National Key Clinical Construction Specialty, Wound Repair and Regeneration Laboratory, Luzhou, Sichuan Province, 646000, China.
| |
Collapse
|
|
16
|
Fujisaki S, Kajiya H, Yanagi T, Maeshiba M, Kakura K, Kido H, Ohno J. Enhancement of jaw bone regeneration via ERK1/2 activation using dedifferentiated fat cells. Cytotherapy 2021; 23:608-616. [PMID: 33863640 DOI: 10.1016/j.jcyt.2021.02.115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 02/19/2021] [Accepted: 02/24/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND AIMS Mesenchymal stem/stromal cells (MSCs) are multipotent and self-renewing cells that are extensively used in tissue engineering. Adipose tissues are known to be the source of two types of MSCs; namely, adipose tissue-derived MSCs (ASCs) and dedifferentiated fat (DFAT) cells. Although ASCs are sometimes transplanted for clinical cytotherapy, the effects of DFAT cell transplantation on mandibular bone healing remain unclear. METHODS The authors assessed whether DFAT cells have osteogenerative potential compared with ASCs in rats in vitro. In addition, to elucidate the ability of DFAT cells to regenerate the jaw bone, the authors examined the effects of DFAT cells on new bone formation in a mandibular defect model in (i) 30-week-old rats and (ii) ovariectomy-induced osteoporotic rats in vivo. RESULTS Osteoblast differentiation with bone morphogenetic protein 2 (BMP-2) or osteogenesis-induced medium upregulated the osteogenesis-related molecules in DFAT cells compared with those in ASCs. BMP-2 activated the phosphorylation signaling pathways of ERK1/2 and Smad2 in DFAT cells, but minor Smad1/5/9 activation was noted in ASCs. The transplantation of DFAT cells into normal or ovariectomy-induced osteoporotic rats with mandibular defects promoted new bone formation compared with that seen with ASCs. CONCLUSIONS DFAT cells promoted osteoblast differentiation and new bone formation through ERK1/2 and Smad2 signaling pathways in vitro. The transplantation of DFAT cells promoted new mandibular bone formation in vivo compared with that seen with ASCs. These results suggest that transplantation of ERK1/2-activated DFAT cells shorten the mandibular bone healing process in cytotherapy.
Collapse
Affiliation(s)
- Seiichi Fujisaki
- Oral Medicine Research Center, Fukuoka Dental College, Fukuoka, Japan; Department of Oral Rehabilitation, Fukuoka Dental College, Fukuoka, Japan
| | - Hiroshi Kajiya
- Oral Medicine Research Center, Fukuoka Dental College, Fukuoka, Japan; Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Japan.
| | - Tsukasa Yanagi
- Department of Oral Rehabilitation, Fukuoka Dental College, Fukuoka, Japan
| | - Munehisa Maeshiba
- Oral Medicine Research Center, Fukuoka Dental College, Fukuoka, Japan; Department of Oral Rehabilitation, Fukuoka Dental College, Fukuoka, Japan
| | - Kae Kakura
- Department of Oral Rehabilitation, Fukuoka Dental College, Fukuoka, Japan
| | - Hirofumi Kido
- Department of Oral Rehabilitation, Fukuoka Dental College, Fukuoka, Japan
| | - Jun Ohno
- Oral Medicine Research Center, Fukuoka Dental College, Fukuoka, Japan
| |
Collapse
|
|
17
|
Balasubramanian B, Liu W, Pushparaj K, Park S. The Epic of In Vitro Meat Production-A Fiction into Reality. Foods 2021; 10:1395. [PMID: 34208720 PMCID: PMC8233867 DOI: 10.3390/foods10061395] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 06/07/2021] [Accepted: 06/09/2021] [Indexed: 01/18/2023] Open
Abstract
Due to a proportionally increasing population and food demands, the food industry has come up with wide innovations, opportunities, and possibilities to manufacture meat under in vitro conditions. The amalgamation of cell culture and tissue engineering has been the base idea for the development of the synthetic meat, and this has been proposed to be a pivotal study for a futuristic muscle development program in the medical field. With improved microbial and chemical advancements, in vitro meat matched the conventional meat and is proposed to be eco-friendly, healthy, nutrient rich, and ethical. Despite the success, there are several challenges associated with the utilization of materials in synthetic meat manufacture, which demands regulatory and safety assessment systems to manage the risks associated with the production of cultured meat. The role of 3D bioprinting meat analogues enables a better nutritional profile and sensorial values. The integration of nanosensors in the bioprocess of culture meat eased the quality assessment throughout the food supply chain and management. Multidisciplinary approaches such as mathematical modelling, computer fluid dynamics, and biophotonics coupled with tissue engineering will be promising aspects to envisage the future prospective of this technology and make it available to the public at economically feasible rates.
Collapse
Affiliation(s)
| | - Wenchao Liu
- Department of Animal Science, College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China;
| | - Karthika Pushparaj
- Department of Zoology, School of Biosciences, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore 641 043, Tamil Nadu, India;
| | - Sungkwon Park
- Department of Food Science and Biotechnology, College of Life Science, Sejong University, Seoul 05006, Korea;
| |
Collapse
|
|
18
|
Guan X, Lei Q, Yan Q, Li X, Zhou J, Du G, Chen J. Trends and ideas in technology, regulation and public acceptance of cultured meat. FUTURE FOODS 2021. [DOI: 10.1016/j.fufo.2021.100032] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
|
|
19
|
Jairath G, Mal G, Gopinath D, Singh B. A holistic approach to access the viability of cultured meat: A review. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2021.02.024] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
|
|
20
|
Nie F, Bi H, Zhang C, Ding P. Differentiation potential and mRNA profiles of human dedifferentiated adipose cells and adipose‑derived stem cells from young donors. Mol Med Rep 2020; 23:47. [PMID: 33200799 PMCID: PMC7705993 DOI: 10.3892/mmr.2020.11685] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 10/27/2020] [Indexed: 12/14/2022] Open
Abstract
Dedifferentiated adipose cells (DAs) and adipose-derived stem cells (ADSCs) are two of the primary types of stem cells derived from adipose tissue, which have been reported to possess similar characteristics, but also exhibit unique phenotypic and functional advantages. However, several reports have described inconsistent results regarding their differences in multilineage differentiation function. Moreover, to the best of our knowledge, there are no studies assessing their myogenic ability, or the differences in the transcriptome between the two cell types derived from lipoaspirates via tumescent liposuction from the same donors. The aim of the present study was to compare the properties and expression profiles of these cell types. Subcutaneous adipose tissue of three female patients (aged 23–30 years) with a physiological BMI (19.1–23.9 kg/m2) were obtained during tumescent liposuction of the abdomen or the thigh. The stromal vascular fraction and mature adipocytes were obtained via collagenase digestion, and ADSCs and DAs were cultured successively. To determine the differences between DAs and ADSCs after 6–7 passages, cell proliferation assays, phenotypic assessment, differentiation assays and high-throughput RNA sequencing (seq) were used. Similar cell morphologies, proliferation dynamics, surface markers and transcriptome expression profiles were observed between the DAs and ADSCs. Whilst there were notable individual differences in the osteogenic, lipogenic, chondrogenic and myogenic abilities of the DAs and ADSCs, it was difficult to determine their differentiation potential based only on the cell source. Interestingly, the myogenic ability was relatively stronger in cells with relatively weaker lipogenic ability. Only 186 differentially expressed genes between the two groups were identified using RNAseq. Several of these genes were involved in biological functions such as transcription regulation, protein translation regulation, cytokine interactions and energy metabolism regulation. The results of the present study suggested a similar functional potential of DAs and ADSCs from young donors undergoing tumescent liposuction operation in regeneration areas and the balance of the differentiative ability of the same cell populations. These data may provide a foundation for further clinical administration of stem cells derived from adipose tissues in therapy.
Collapse
Affiliation(s)
- Fangfei Nie
- Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China
| | - Hongsen Bi
- Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China
| | - Chen Zhang
- Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China
| | - Pengbing Ding
- Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, P.R. China
| |
Collapse
|
|
21
|
Hagiwara R, Oki Y, Matsumaru T, Ibayashi S, Kano K. Generation of metabolically functional hepatocyte-like cells from dedifferentiated fat cells by Foxa2, Hnf4a and Sall1 transduction. Genes Cells 2020; 25:811-824. [PMID: 33064855 PMCID: PMC7894465 DOI: 10.1111/gtc.12814] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 10/10/2020] [Accepted: 10/10/2020] [Indexed: 01/17/2023]
Abstract
Mature adipocyte-derived dedifferentiated fat (DFAT) cells have been identified to possess similar multipotency to mesenchymal stem cells, but a method for converting DFAT cells into hepatocytes was previously unknown. Here, using comprehensive analysis of gene expression profiles, we have extracted three transcription factors, namely Foxa2, Hnf4a and Sall1 (FHS), that can convert DFAT cells into hepatocytes. Hepatogenic induction has converted FHS-infected DFAT cells into an epithelial-like morphological state and promoted the expression of hepatocyte-specific features. Furthermore, the DFAT-derived hepatocyte-like (D-Hep) cells catalyzed the detoxification of several compounds. These results indicate that the transduction of DFAT cells with three genes, which were extracted by comprehensive gene expression analysis, efficiently generated D-Hep cells with detoxification abilities similar to those of primary hepatocytes. Thus, D-Hep cells may be useful as a new cell source for surrogate hepatocytes and may be applied to drug discovery studies, such as hepatotoxicity screening and drug metabolism tests.
Collapse
Affiliation(s)
- Reiko Hagiwara
- Laboratory of Cell and Tissue Biology, Graduate School of Bioresource Sciences, Nihon University, Fujisawa, Japan
| | - Yoshinao Oki
- Laboratory of Cell and Tissue Biology, Graduate School of Bioresource Sciences, Nihon University, Fujisawa, Japan
| | - Takashi Matsumaru
- Laboratory of Cell and Tissue Biology, Graduate School of Bioresource Sciences, Nihon University, Fujisawa, Japan
| | - Shiho Ibayashi
- Laboratory of Cell and Tissue Biology, Graduate School of Bioresource Sciences, Nihon University, Fujisawa, Japan
| | - Koichiro Kano
- Laboratory of Cell and Tissue Biology, Graduate School of Bioresource Sciences, Nihon University, Fujisawa, Japan
| |
Collapse
|
|
22
|
Gao L, Yang M, Wei Z, Gu M, Yang L, Bai C, Wu Y, Li G. MSTN Mutant Promotes Myogenic Differentiation by Increasing Demethylase TET1 Expression via the SMAD2/SMAD3 Pathway. Int J Biol Sci 2020; 16:1324-1334. [PMID: 32210722 PMCID: PMC7085230 DOI: 10.7150/ijbs.40551] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 01/31/2020] [Indexed: 12/20/2022] Open
Abstract
Myostatin (MSTN) is mostly expressed in skeletal muscle and plays crucial roles in the negative regulation of muscle mass development. The methylation and demethylation of myogenesis-specific genes are major regulatory factors in muscle satellite cell differentiation. The present study was designed to investigate the mechanism of myogenic differentiation regulated by MSTN mutation (MT) and the methylation/demethylation state of downstream genes. The results showed that, in the MSTN-/+ satellite cells, a higher myotube fusion index and a larger myotube length were observed compared to the wild type controls; the genes associated with myogenesis were all up-regulated compared to the WT controls. The methylation of the promoters and gene bodies of PAX3, PAX7, MyoD, and MyoG were all down-regulated, while the expression of the key demethylase TET1 was significantly promoted. ChIP-qPCR was used to demonstrate that the SMAD2/SMAD3 complex combined with the promoter of TET1 to inhibit the activity of TET1 promoter, indicating that MSTN may regulate TET1 via SMAD2/SMAD3. The overexpression of TET1 in wild type cells promoted myogenic differentiation, increased the myotube index, and reduced the methylation of the associated genes. On the contrary, the knockdown of TET1 in the MSTN mutant cells resulted in the opposite phenomena as in the overexpressed cells. In conclusion, the myostatin mutant showed an increased transcriptional activity of TET1, inducing higher levels of demethylation and improving the transcriptional activity levels of myogenic differentiation-associated genes. The binding of SMAD2/SMAD3 directly to the TET1 promoter region indicated that the MSTN mutant demethylated the myogenesis-specific genes by up-regulating TET1, which is directly controlled by SMAD2/SMAD3.
Collapse
Affiliation(s)
- Li Gao
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, 010070, China
| | - Miaomiao Yang
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, 010070, China
| | - Zhuying Wei
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, 010070, China.,School of Life Science, Inner Mongolia University, Hohhot, 010070, China
| | - Mingjuan Gu
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, 010070, China
| | - Lei Yang
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, 010070, China
| | - Chunling Bai
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, 010070, China.,School of Life Science, Inner Mongolia University, Hohhot, 010070, China
| | - Yunxi Wu
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, 010070, China.,School of Life Science, Inner Mongolia University, Hohhot, 010070, China
| | - Guangpeng Li
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, 010070, China.,School of Life Science, Inner Mongolia University, Hohhot, 010070, China
| |
Collapse
|
|
23
|
Gene expression profiles of early chondrogenic markers in dedifferentiated fat cells stimulated by bone morphogenetic protein 4 under monolayer and spheroid culture conditions in vitro. ACTA ACUST UNITED AC 2019. [DOI: 10.1016/j.odw.2016.10.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
24
|
Tateno A, Asano M, Akita D, Toriumi T, Tsurumachi-Iwasaki N, Kazama T, Arai Y, Matsumoto T, Kano K, Honda M. Transplantation of dedifferentiated fat cells combined with a biodegradable type I collagen-recombinant peptide scaffold for critical-size bone defects in rats. J Oral Sci 2019; 61:534-538. [PMID: 31631097 DOI: 10.2334/josnusd.18-0458] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
Tissue engineering is a promising approach to supplement existing treatment strategies for craniofacial bone regeneration. In this study, a type I collagen scaffold made from a recombinant peptide (RCP) with an Arg-Gly-Asp motif was developed, and its effect on regeneration in critical-size mandibular bone defects was evaluated. Additionally, the combined effect of the scaffold and lipid-free dedifferentiated fat (DFAT) cells was assessed. Briefly, DFAT cells were separated from mature adipocytes by using a ceiling culture technique based on buoyancy. A 3 cm × 4 cm critical-size bone defect was created in the rat mandible, and regeneration was evaluated by using RCP with DFAT cells. Then, cultured DFAT cells and adipose-derived stem cells (ASCs) were seeded onto RCP scaffolds (DFAT/RCP and ASC/RCP) and implanted into the bone defects. Micro-computed tomography imaging at 8 weeks after implantation showed significantly greater bone regeneration in the DFAT/RCP group than in the ASC/RCP and RCP-alone groups. Similarly, histological analysis showed significantly greater bone width in the DFAT/RCP group than in the ASC/RCP and RCP-alone groups. These findings suggest that DFAT/RCP is effective for bone formation in critical-size bone defects and that DFAT cells are a promising source for bone regeneration.
Collapse
Affiliation(s)
- Atsushi Tateno
- Division of Applied Oral Sciences, Nihon University Graduate School of Dentistry
| | - Masatake Asano
- Department of Pathology, Nihon University School of Dentistry.,Division of Immunology and Pathobiology, Dental Research Center, Nihon University School of Dentistry
| | - Daisuke Akita
- Department of Partial Denture Prosthodontics, Nihon University School of Dentistry
| | - Taku Toriumi
- Department of Oral Anatomy, Aichi Gakuin University School of Dentistry
| | | | - Tomohiko Kazama
- Department of Functional Morphology, Division of Cell Regeneration and Transplantation, Nihon University School of Medicine
| | - Yoshinori Arai
- Department of Oral and Maxillofacial Radiology, Nihon University School of Dentistry
| | - Taro Matsumoto
- Department of Functional Morphology, Division of Cell Regeneration and Transplantation, Nihon University School of Medicine
| | - Koichiro Kano
- Laboratory of Cell and Tissue Biology, College of Bioresource Sciences, Nihon University
| | - Masaki Honda
- Department of Oral Anatomy, Aichi Gakuin University School of Dentistry
| |
Collapse
|
|
25
|
Deng Z, Zou J, Wang W, Nie Y, Tung WT, Ma N, Lendlein A. Dedifferentiation of mature adipocytes with periodic exposure to cold. Clin Hemorheol Microcirc 2019; 71:415-424. [PMID: 31006679 DOI: 10.3233/ch-199005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Lipid-containing adipocytes can dedifferentiate into fibroblast-like cells under appropriate culture conditions, which are known as dedifferentiated fat (DFAT) cells. However, the relative low dedifferentiation efficiency with the established protocols limit their widespread applications. In this study, we found that adipocyte dedifferentiation could be promoted via periodic exposure to cold (10°C) in vitro. The lipid droplets in mature adipocytes were reduced by culturing the cells in periodic cooling/heating cycles (10-37°C) for one week. The periodic temperature change led to the down-regulation of the adipogenic genes (FABP4, Leptin) and up-regulation of the mitochondrial uncoupling related genes (UCP1, PGC-1α, and PRDM16). In addition, the enhanced expression of the cell proliferation marker Ki67 was observed in the dedifferentiated fibroblast-like cells after periodic exposure to cold, as compared to the cells cultured in 37°C. Our in vitro model provides a simple and effective approach to promote lipolysis and can be used to improve the dedifferentiation efficiency of adipocytes towards multipotent DFAT cells.
Collapse
Affiliation(s)
- Zijun Deng
- Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany.,Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany
| | - Jie Zou
- Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany.,Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany
| | - Weiwei Wang
- Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany
| | - Yan Nie
- Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany.,Institute of Biochemistry and Biology, University of Potsdam, Potsdam, Germany
| | - Wing-Tai Tung
- Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany.,Institute of Biochemistry and Biology, University of Potsdam, Potsdam, Germany
| | - Nan Ma
- Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany.,Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.,Helmholtz Virtual Institute - Multifunctional Biomaterials for Medicine, Berlin and Teltow, Teltow, Germany
| | - Andreas Lendlein
- Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany.,Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.,Institute of Biochemistry and Biology, University of Potsdam, Potsdam, Germany.,Helmholtz Virtual Institute - Multifunctional Biomaterials for Medicine, Berlin and Teltow, Teltow, Germany
| |
Collapse
|
|
26
|
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]
|
|
27
|
Breuls N, Giacomazzi G, Sampaolesi M. (Epi)genetic Modifications in Myogenic Stem Cells: From Novel Insights to Therapeutic Perspectives. Cells 2019; 8:cells8050429. [PMID: 31075875 PMCID: PMC6562881 DOI: 10.3390/cells8050429] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 05/06/2019] [Accepted: 05/07/2019] [Indexed: 12/17/2022] Open
Abstract
The skeletal muscle is considered to be an ideal target for stem cell therapy as it has an inherent regenerative capacity. Upon injury, the satellite cells, muscle stem cells that reside under the basal lamina of the myofibres, start to differentiate in order to reconstitute the myofibres while maintaining the initial stem cell pool. In recent years, it has become more and more evident that epigenetic mechanisms such as histon modifications, DNA methylations and microRNA modulations play a pivatol role in this differentiation process. By understanding the mechanisms behind myogenesis, researchers are able to use this knowledge to enhance the differentiation and engraftment potential of different muscle stem cells. Besides manipulation on an epigenetic level, recent advances in the field of genome-engineering allow site-specific modifications in the genome of these stem cells. Combining epigenetic control of the stem cell fate with the ability to site-specifically correct mutations or add genes for further cell control, can increase the use of stem cells as treatment of muscular dystrophies drastically. In this review, we will discuss the advances that have been made in genome-engineering and the epigenetic regulation of muscle stem cells and how this knowledge can help to get stem cell therapy to its full potential.
Collapse
Affiliation(s)
- Natacha Breuls
- Translational Cardiomyology Lab, Department of Development and Regeneration, Stem Cell Institute Leuven, 3000 KU Leuven, Belgium.
| | - Giorgia Giacomazzi
- Translational Cardiomyology Lab, Department of Development and Regeneration, Stem Cell Institute Leuven, 3000 KU Leuven, Belgium.
| | - Maurilio Sampaolesi
- Translational Cardiomyology Lab, Department of Development and Regeneration, Stem Cell Institute Leuven, 3000 KU Leuven, Belgium.
- Human Anatomy Unit, Department of Public Health, Experimental and Forensic Medicine, and Interuniversity Institute of Myology, University of Pavia, 27100 Pavia, Italy.
| |
Collapse
|
|
28
|
Megakaryocytes and platelets from a novel human adipose tissue-derived mesenchymal stem cell line. Blood 2018; 133:633-643. [PMID: 30487128 DOI: 10.1182/blood-2018-04-842641] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Accepted: 10/02/2018] [Indexed: 12/24/2022] Open
Abstract
The clinical need for platelet transfusions is increasing; however, donor-dependent platelet transfusions are associated with practical problems, such as the limited supply and the risk of infection. Thus, we developed a manufacturing system for platelets from a donor-independent cell source: a human adipose-derived mesenchymal stromal/stem cell line (ASCL). The ASCL was obtained using an upside-down culture flask method and satisfied the minimal criteria for defining mesenchymal stem cells (MSCs) by The International Society for Cellular Therapy. The ASCL showed its proliferation capacity for ≥2 months without any abnormal karyotypes. The ASCL was cultured in megakaryocyte induction media. ASCL-derived megakaryocytes were obtained, with a peak at day 8 of culture, and ASCL-derived platelets (ASCL-PLTs) were obtained, with a peak at day 12 of culture. We observed that CD42b+ cells expressed an MSC marker (CD90) which is related to cell adhesion. Compared with peripheral platelets, ASCL-PLTs exhibit higher levels of PAC1 binding, P-selectin surface exposure, ristocetin-induced platelet aggregation, and ADP-induced platelet aggregation, as well as similar levels of fibrinogen binding and collagen-induced platelet aggregation. ASCL-PLTs have lower epinephrine-induced platelet aggregation. The pattern of in vivo kinetics after infusion into irradiated immunodeficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice was similar to that of platelet concentrates. ASCL-PLTs have similar characteristics to those of peripheral platelets and might have an additional function as MSCs. The establishment of the ASCL and its differentiation into ASCL-PLTs do not require gene transfer, and endogenous thrombopoietin is used for differentiation. The present protocol is a simple method that does not require feeder cells, further enhancing the clinical application of our approach.
Collapse
|
|
29
|
Abstract
Adipogenesis is a complex process whereby the multipotent adipose-derived stem cell is converted to a preadipocyte before terminal differentiation into the mature adipocyte. Preadipocytes are present throughout adult life, exhibit adipose fat depot specificity, and differentiate and proliferate from distinct progenitor cells. The mechanisms that promote preadipocyte commitment and maturation involve numerous protein factor regulators, epigenetic factors, and miRNAs. Detailed characterization of this process is currently an area of intense research and understanding the roles of preadipocytes in tissue plasticity may provide insight into novel approaches for tissue engineering, regenerative medicine and treating a host of obesity-related conditions. In the current study, we analyzed the current literature and present a review of the characteristics of transitioning adipocytes and detail how local microenvironments influence their progression towards terminal differentiation and maturation. Specifically, we detail the characterization of preadipocyte via surface markers, examine the signaling cascades and regulation behind adipogenesis and cell maturation, and survey their role in tissue plasticity and health and disease.
Collapse
|
|
30
|
Abstract
During the last decades, research on adipose tissues has spread in parallel with the extension of obesity. Several observations converged on the idea that adipose tissues are organized in a large organ with endocrine and plastic properties. Two parenchymal components: white (WATs) and brown adipose tissues (BATs) are contained in subcutaneous and visceral compartments. Although both have endocrine properties, their function differs: WAT store lipids to allow intervals between meals, BAT burns lipids for thermogenesis. In spite of these opposite functions, they share the ability for reciprocal reversible transdifferentiation to tackle special physiologic needs. Thus, chronic need for thermogenesis induces browning and chronic positive energy balance induce whitening. Lineage tracing and data from explant studies strongly suggest other remodeling properties of this organ. During pregnancy and lactation breast WAT transdifferentiates into milk-secreting glands, composed by cells with abundant cytoplasmic lipids (pink adipocytes) and in the postlactation period pink adipocytes transdifferentiate back into WAT and BAT. The plastic properties of mature adipocytes are supported also by a liposecretion process in vitro where adult cell in culture transdifferentiate to differentiated fibroblast-like elements able to give rise to different phenotypes (rainbow adipocytes). In addition, the inflammasome system is activated in stressed adipocytes from obese adipose tissue. These adipocytes die and debris are reabsorbed by macrophages inducing a chronic low-grade inflammation, potentially contributing to insulin resistance and T2 diabetes. Thus, the plastic properties of this organ could open new therapeutic perspectives in the obesity-related metabolic disease and in breast pathologies. © 2018 American Physiological Society. Compr Physiol 8:1357-1431, 2018.
Collapse
Affiliation(s)
- Saverio Cinti
- Professor of Human Anatomy, Director, Center of Obesity, University of Ancona (Politecnica delle Marche), Ancona, Italy
| |
Collapse
|
|
31
|
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.
Collapse
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
| |
Collapse
|
|
32
|
Duarte MS, Bueno R, Silva W, Campos CF, Gionbelli MP, Guimarães SEF, Silva FF, Lopes PS, Hausman GJ, Dodson MV. TRIENNIAL GROWTH AND DEVELOPMENT SYMPOSIUM: Dedifferentiated fat cells: Potential and perspectives for their use in clinical and animal science purpose. J Anim Sci 2017; 95:2255-2260. [PMID: 28727019 DOI: 10.2527/jas.2016.1094] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
An increasing body of evidences has demonstrated the ability of the mature adipocyte to dedifferentiate into a population of proliferative-competent cells known as dedifferentiated fat (DFAT) cells. As early as the 1970s, in vitro studies showed that DFAT cells may be obtained by ceiling culture, which takes advantage of the buoyancy property of lipid-filled cells. It was documented that DFAT cells may acquire a phenotype similar to mesenchymal stem cells and yet may differentiate into multiple cell lineages, such as skeletal and smooth muscle cells, cardiomyocytes, osteoblasts, and adipocytes. Additionally, recent studies showed the ability of isolated mature adipocytes to dedifferentiate in vivo and the capacity of the progeny cells to redifferentiate into mature adipocytes, contributing to the increase of body fatness. These findings shed light on the potential for use of DFAT cells, not only for clinical purposes but also within the animal science field, because increasing intramuscular fat without excessive increase in other fat depots is a challenge in livestock production. Knowledge of the mechanisms underlying the dedifferentiation and redifferentiation of DFAT cells will allow the development of strategies for their use for clinical and animal science purposes. In this review, we highlight several aspects of DFAT cells, their potential for clinical purposes, and their contribution to adipose tissue mass in livestock.
Collapse
|
|
33
|
Maurizi G, Poloni A, Mattiucci D, Santi S, Maurizi A, Izzi V, Giuliani A, Mancini S, Zingaretti MC, Perugini J, Severi I, Falconi M, Vivarelli M, Rippo MR, Corvera S, Giordano A, Leoni P, Cinti S. Human White Adipocytes Convert Into "Rainbow" Adipocytes In Vitro. J Cell Physiol 2017; 232:2887-2899. [PMID: 27987321 DOI: 10.1002/jcp.25743] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Accepted: 12/15/2016] [Indexed: 12/30/2022]
Abstract
White adipocytes are plastic cells able to reversibly transdifferentiate into brown adipocytes and into epithelial glandular cells under physiologic stimuli in vivo. These plastic properties could be used in future for regenerative medicine, but are incompletely explored in their details. Here, we focused on plastic properties of human mature adipocytes (MA) combining gene expression profile through microarray analysis with morphologic data obtained by electron and time lapse microscopy. Primary MA showed the classic morphology and gene expression profile of functional mature adipocytes. Notably, despite their committed status, MA expressed high levels of reprogramming genes. MA from ceiling cultures underwent transdifferentiation toward fibroblast-like cells with a well-differentiated morphology and maintaining stem cell gene signatures. The main morphologic aspect of the transdifferentiation process was the secretion of large lipid droplets and the development of organelles necessary for exocrine secretion further supported the liposecretion process. Of note, electron microscope findings suggesting liposecretion phenomena were found also in explants of human fat and rarely in vivo in fat biopsies from obese patients. In conclusion, both MA and post-liposecretion adipocytes show a well-differentiated phenotype with stem cell properties in line with the extraordinary plasticity of adipocytes in vivo. J. Cell. Physiol. 232: 2887-2899, 2017. © 2016 Wiley Periodicals, Inc.
Collapse
MESH Headings
- Adipocytes, Brown/metabolism
- Adipocytes, Brown/ultrastructure
- Adipocytes, White/metabolism
- Adipocytes, White/ultrastructure
- Adipogenesis
- Aged
- Aged, 80 and over
- Cell Lineage
- Cell Plasticity
- Cell Shape
- Cells, Cultured
- Cellular Reprogramming
- Gene Expression Profiling/methods
- Gene Expression Regulation, Developmental
- Genetic Markers
- Humans
- Lipid Droplets/metabolism
- Lipid Metabolism
- Mesenchymal Stem Cells/metabolism
- Mesenchymal Stem Cells/ultrastructure
- Microscopy, Confocal
- Microscopy, Electron
- Microscopy, Video
- Middle Aged
- Obesity/metabolism
- Obesity/pathology
- Obesity/physiopathology
- Oligonucleotide Array Sequence Analysis
- Phenotype
- Time Factors
- Time-Lapse Imaging
Collapse
Affiliation(s)
- Giulia Maurizi
- Dipartimento Scienze Cliniche e Molecolari, Clinica di Ematologia, Università Politecnica delle Marche, Ancona, Italy
| | - Antonella Poloni
- Dipartimento Scienze Cliniche e Molecolari, Clinica di Ematologia, Università Politecnica delle Marche, Ancona, Italy
| | - Domenico Mattiucci
- Dipartimento Scienze Cliniche e Molecolari, Clinica di Ematologia, Università Politecnica delle Marche, Ancona, Italy
| | - Spartaco Santi
- Istituto di Genetica Molecolare del CNR, Laboratorio di Biologia Cellulare Muscoloscheletrica, Istituti Ortopedici Rizzoli, Bologna, Italy
| | - Angela Maurizi
- Dipartimento di Medicina Sperimentale e Clinica, Clinica Chirurgia del Pancreas, Università Politecnica delle Marche, Ancona, Italy
| | - Valerio Izzi
- Faculty of Biochemistry and Molecular Medicine, Center for Cell-Matrix Research and Biocenter Oulu, University of Oulu, Oulu, Finland
| | - Angelica Giuliani
- Dipartimento Scienze Cliniche e Molecolari, Laboratorio di Patologia Sperimentale, Ancona, Italy
| | - Stefania Mancini
- Dipartimento Scienze Cliniche e Molecolari, Clinica di Ematologia, Università Politecnica delle Marche, Ancona, Italy
| | - Maria Cristina Zingaretti
- Dipartimento di Medicina Sperimentale e Clinica, Center of Obesity, Università Politecnica delle Marche, Ancona, Italy
| | - Jessica Perugini
- Dipartimento di Medicina Sperimentale e Clinica, Center of Obesity, Università Politecnica delle Marche, Ancona, Italy
| | - Ilenia Severi
- Dipartimento di Medicina Sperimentale e Clinica, Center of Obesity, Università Politecnica delle Marche, Ancona, Italy
| | - Massimo Falconi
- Dipartimento di Medicina Sperimentale e Clinica, Clinica Chirurgia del Pancreas, Università Politecnica delle Marche, Ancona, Italy
| | - Marco Vivarelli
- Department of Experimental and Clinical Medicine, Hepatobiliary and Abdominal Transplantation Surgery, Università Politecnica delle Marche, Ancona, Italy
| | - Maria Rita Rippo
- Dipartimento Scienze Cliniche e Molecolari, Laboratorio di Patologia Sperimentale, Ancona, Italy
| | - Silvia Corvera
- Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
| | - Antonio Giordano
- Dipartimento di Medicina Sperimentale e Clinica, Center of Obesity, Università Politecnica delle Marche, Ancona, Italy
| | - Pietro Leoni
- Dipartimento Scienze Cliniche e Molecolari, Clinica di Ematologia, Università Politecnica delle Marche, Ancona, Italy
| | - Saverio Cinti
- Dipartimento di Medicina Sperimentale e Clinica, Center of Obesity, Università Politecnica delle Marche, Ancona, Italy
| |
Collapse
|
|
34
|
Dedifferentiated Adipocytes Promote Adipose Tissue Generation within an External Suspension Device. Plast Reconstr Surg 2017; 140:525-536. [DOI: 10.1097/prs.0000000000003601] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
|
|
35
|
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.
Collapse
|
|
36
|
Vicente-García C, Villarejo-Balcells B, Irastorza-Azcárate I, Naranjo S, Acemel RD, Tena JJ, Rigby PWJ, Devos DP, Gómez-Skarmeta JL, Carvajal JJ. Regulatory landscape fusion in rhabdomyosarcoma through interactions between the PAX3 promoter and FOXO1 regulatory elements. Genome Biol 2017; 18:106. [PMID: 28615069 PMCID: PMC5470208 DOI: 10.1186/s13059-017-1225-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 04/28/2017] [Indexed: 12/25/2022] Open
Abstract
Background The organisation of vertebrate genomes into topologically associating domains (TADs) is believed to facilitate the regulation of the genes located within them. A remaining question is whether TAD organisation is achieved through the interactions of the regulatory elements within them or if these interactions are favoured by the pre-existence of TADs. If the latter is true, the fusion of two independent TADs should result in the rewiring of the transcriptional landscape and the generation of ectopic contacts. Results We show that interactions within the PAX3 and FOXO1 domains are restricted to their respective TADs in normal conditions, while in a patient-derived alveolar rhabdomyosarcoma cell line, harbouring the diagnostic t(2;13)(q35;q14) translocation that brings together the PAX3 and FOXO1 genes, the PAX3 promoter interacts ectopically with FOXO1 sequences. Using a combination of 4C-seq datasets, we have modelled the three-dimensional organisation of the fused landscape in alveolar rhabdomyosarcoma. Conclusions The chromosomal translocation that leads to alveolar rhabdomyosarcoma development generates a novel TAD that is likely to favour ectopic PAX3:FOXO1 oncogene activation in non-PAX3 territories. Rhabdomyosarcomas may therefore arise from cells which do not normally express PAX3. The borders of this novel TAD correspond to the original 5'- and 3'- borders of the PAX3 and FOXO1 TADs, respectively, suggesting that TAD organisation precedes the formation of regulatory long-range interactions. Our results demonstrate that, upon translocation, novel regulatory landscapes are formed allowing new intra-TAD interactions between the original loci involved. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1225-z) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Cristina Vicente-García
- Centro Andaluz de Biología del Desarrollo (CABD), CSIC-UPO-JA, Universidad Pablo de Olavide, Carretera de Utrera km1, 41013, Seville, Spain
| | - Barbara Villarejo-Balcells
- Division of Cancer Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK
| | - Ibai Irastorza-Azcárate
- Centro Andaluz de Biología del Desarrollo (CABD), CSIC-UPO-JA, Universidad Pablo de Olavide, Carretera de Utrera km1, 41013, Seville, Spain
| | - Silvia Naranjo
- Centro Andaluz de Biología del Desarrollo (CABD), CSIC-UPO-JA, Universidad Pablo de Olavide, Carretera de Utrera km1, 41013, Seville, Spain
| | - Rafael D Acemel
- Centro Andaluz de Biología del Desarrollo (CABD), CSIC-UPO-JA, Universidad Pablo de Olavide, Carretera de Utrera km1, 41013, Seville, Spain
| | - Juan J Tena
- Centro Andaluz de Biología del Desarrollo (CABD), CSIC-UPO-JA, Universidad Pablo de Olavide, Carretera de Utrera km1, 41013, Seville, Spain
| | - Peter W J Rigby
- Division of Cancer Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK
| | - Damien P Devos
- Centro Andaluz de Biología del Desarrollo (CABD), CSIC-UPO-JA, Universidad Pablo de Olavide, Carretera de Utrera km1, 41013, Seville, Spain
| | - Jose L Gómez-Skarmeta
- Centro Andaluz de Biología del Desarrollo (CABD), CSIC-UPO-JA, Universidad Pablo de Olavide, Carretera de Utrera km1, 41013, Seville, Spain
| | - Jaime J Carvajal
- Centro Andaluz de Biología del Desarrollo (CABD), CSIC-UPO-JA, Universidad Pablo de Olavide, Carretera de Utrera km1, 41013, Seville, Spain.
| |
Collapse
|
|
37
|
Hao W, Jiang C, Jiang M, Wang T, Wang X. Osteogenic potency of dedifferentiated fat cells isolated from elderly people with osteoporosis. Exp Ther Med 2017; 14:43-50. [PMID: 28672891 PMCID: PMC5488489 DOI: 10.3892/etm.2017.4465] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Accepted: 01/26/2017] [Indexed: 12/13/2022] Open
Abstract
Mature adipocytes are the major cell type in adipose tissue. This study aimed to explore the osteogenic potency of dedifferentiated fat cells obtained from osteoporotic patients (opDFATs) in vitro and in vivo. Mature adipocytes and adipose-derived stem cells (opASCs) were harvested from subcutaneous adipose tissue. Mature adipocytes were dedifferentiated to produce opDFATs by the ceiling culture method. OpDFATs were osteogenically induced in vitro with opASCs as a control. Cell growth, alkaline phosphatase (ALPase) activity and cell mineralization were determined, and expression levels of osteogenesis-specific genes (collagen I, osteocalcin and bone sialoprotein) were analyzed using quantitative reverse transcription polymerase chain reaction. After 14 days, the opDFATs were combined with a poly(lactide-co-glycolide)-β-tricalcium phosphate porous scaffold after being suspended in collagen I gel and implanted into nude mice for 4 weeks prior to histological analysis. Unilocular lipid droplets in mature adipocytes gradually split into smaller droplets and disappeared from the cytoplasm. Mature adipocytes dedifferentiated to opDFATs and cell morphology changed from spherical to elongated. High levels of ALPase and cell mineralization were observed in opDFATs by staining. No significant differences were found between the growth curves, ALPase activity, cell mineralization and expression levels of osteogenesis-specific genes between opDFATS and opASCs. After implantation for 4 weeks, new bone tissue was observed histologically in the opDFATs-based biocomposite. OpDFATs are implicated as a novel type of seed cell for bone tissue engineering based on their osteogenic potency and higher abundance in adipose tissue compared with opASCs.
Collapse
Affiliation(s)
- Wei Hao
- Department of Orthopedics and Traumatology, Yantai Yuhuangding Hospital Affiliated to Qingdao University Medical College, Yantai, Shandong 264000, P.R. China
| | - Chuanqiang Jiang
- Department of Orthopedics and Traumatology, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China
| | - Ming Jiang
- Department of Stomatology, 107 Hospital of Jinan Military Area, Yantai, Shandong 264002, P.R. China
| | - Tian Wang
- Department of Pharmacology, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China
| | - Xin Wang
- Department of Orthopedics and Traumatology, Yantai Yuhuangding Hospital Affiliated to Qingdao University Medical College, Yantai, Shandong 264000, P.R. China
| |
Collapse
|
|
38
|
Maurizi G, Della Guardia L, Maurizi A, Poloni A. Adipocytes properties and crosstalk with immune system in obesity-related inflammation. J Cell Physiol 2017; 233:88-97. [PMID: 28181253 DOI: 10.1002/jcp.25855] [Citation(s) in RCA: 169] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 02/07/2017] [Indexed: 12/11/2022]
Abstract
Obesity is a condition likely associated with several dysmetabolic conditions or worsening of cardiovascular and other chronic disturbances. A key role in this mechanism seem to be played by the onset of low-grade systemic inflammation, highlighting the importance of the interplay between adipocytes and immune system cells. Adipocytes express a complex and highly adaptive biological profile being capable to selectively activate different metabolic pathways in order to respond to environmental stimuli. It has been demonstrated how adipocytes, under appropriate stimulation, can easily differentiate and de-differentiate thereby converting themselves into different phenotypes according to metabolic necessities. Although underlying mechanisms are not fully understood, growing in adipocyte size and the inability of storing triglycerides under overfeeding conditions seem to be crucial for the switching to a dysfunctional metabolic profile, which is characterized by inflammatory and apoptotic pathways activation, and by the shifting to pro-inflammatory adipokines secretion. In obesity, changes in adipokines secretion along with adipocyte deregulation and fatty acids release into circulation contribute to maintain immune cells activation as well as their infiltration into regulatory organs. Over the well-established role of macrophages, recent findings suggest the involvement of new classes of immune cells such as T regulatory lymphocytes and neutrophils in the development inflammation and multi systemic worsening. Deeply understanding the pathways of adipocyte regulation and the de-differentiation process could be extremely useful for developing novel strategies aimed at curbing obesity-related inflammation and related metabolic disorders.
Collapse
Affiliation(s)
- Giulia Maurizi
- Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy
| | - Lucio Della Guardia
- Dipartimento di Sanità Pubblica, Medicina Sperimentale e Forense, Unità di Scienza dell'Alimentazione, Università degli studi di Pavia, Pavia, Italy
| | - Angela Maurizi
- Chirurgia d'Urgenza e del Trauma, Azienda Ospedaliera Universitaria-Ospedali Riuniti di Ancona, Ancona, Italy
| | - Antonella Poloni
- Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy
| |
Collapse
|
|
39
|
Shah M, George RL, Evancho-Chapman MM, Zhang G. Current challenges in dedifferentiated fat cells research. Organogenesis 2016; 12:119-127. [PMID: 27322672 DOI: 10.1080/15476278.2016.1197461] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Dedifferentiated fat cells show great promises as a novel cell source for stem cell research. It has many advantages when used for cell-based therapeutics including abundance, pluripotency, and safety. However, there are many obstacles researchers need to overcome to make the next big move in DFAT cells research. In this review, we summarize the current main challenges in DFAT cells research including cell culture purity, phenotypic properties, and dedifferentiation mechanisms. The common methods to produce DFAT cells as well as the cell purity issue during DFAT cell production have been introduced. Current approaches to improve DFAT cell purity have been discussed. The phenotypic profile of DFAT cells have been listed and compared with other stem cells. Further studies on elucidating the underlying dedifferentiation mechanisms will dramatically advance DFAT cell research.
Collapse
Affiliation(s)
- Mickey Shah
- a Integrated Bioscience Program , The University of Akron , Akron , OH , USA.,b Department of Biomedical Engineering , The University of Akron , Akron , OH , USA
| | - Richard L George
- c Department of Surgery , Summa Health System , Akron , OH , USA.,d Department of Surgery , Northeast Ohio Medical University , Rootstown , OH , USA
| | | | - Ge Zhang
- b Department of Biomedical Engineering , The University of Akron , Akron , OH , USA
| |
Collapse
|
|
40
|
Deng B, Zhang F, Chen K, Wen J, Huang H, Liu W, Ye S, Wang L, Yang Y, Gong P, Jiang S. MyoD promotes porcine PPARγ gene expression through an E-box and a MyoD-binding site in the PPARγ promoter region. Cell Tissue Res 2016; 365:381-91. [PMID: 26944559 DOI: 10.1007/s00441-016-2380-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Accepted: 02/18/2016] [Indexed: 01/08/2023]
Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) is a key transcription factor in adipogenesis and can be regulated by adipogenesis-related factors. However, little information is available regarding its regulation by myogenic factors. In this study, we found that over-expression of MyoD enhanced porcine adipocyte differentiation and up-regulated PPARγ expression, whereas small interfering RNA against MyoD significantly attenuated porcine adipocyte differentiation and inhibited PPARγ expression. The MyoD-binding sites in the PPARγ promoter region at -412 to -396 and -155 to -150 were identified by promoter deletion analysis and site-directed mutagenesis. Electrophoretic mobility shift assays and chromatin immunoprecipitation further showed that these two regions are MyoD-binding sites, both in vitro and in vivo, indicating that MyoD directly interacts with the porcine PPARγ promoter. Thus, our results demonstrate that an Enhancer box and a binding site for a cooperative co-activator of MyoD are present in the promoter region of porcine PPARγ; furthermore, MyoD up-regulates PPARγ expression and promotes porcine adipocyte differentiation.
Collapse
Affiliation(s)
- Bing Deng
- Wuhan Institute of Animal Husbandry and Veterinary Science, Wuhan Academy of Agricultural Science and Technology, Wuhan, Hubei, 430208, Peoples Republic of China
| | - Feng Zhang
- Key Laboratory of Swine Genetics and Breeding of the Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, Peoples Republic of China
| | - Kun Chen
- Key Laboratory of Swine Genetics and Breeding of the Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, Peoples Republic of China
| | - Jianghui Wen
- Wuhan University of Technology, Wuhan, 430074, Peoples Republic of China
| | - Haijun Huang
- Wuhan Institute of Animal Husbandry and Veterinary Science, Wuhan Academy of Agricultural Science and Technology, Wuhan, Hubei, 430208, Peoples Republic of China
| | - Wu Liu
- Wuhan Institute of Animal Husbandry and Veterinary Science, Wuhan Academy of Agricultural Science and Technology, Wuhan, Hubei, 430208, Peoples Republic of China
| | - Shengqiang Ye
- Wuhan Institute of Animal Husbandry and Veterinary Science, Wuhan Academy of Agricultural Science and Technology, Wuhan, Hubei, 430208, Peoples Republic of China
| | - Lixia Wang
- Wuhan Institute of Animal Husbandry and Veterinary Science, Wuhan Academy of Agricultural Science and Technology, Wuhan, Hubei, 430208, Peoples Republic of China
| | - Yu Yang
- Wuhan Institute of Animal Husbandry and Veterinary Science, Wuhan Academy of Agricultural Science and Technology, Wuhan, Hubei, 430208, Peoples Republic of China
| | - Ping Gong
- Wuhan Institute of Animal Husbandry and Veterinary Science, Wuhan Academy of Agricultural Science and Technology, Wuhan, Hubei, 430208, Peoples Republic of China
| | - Siwen Jiang
- Key Laboratory of Swine Genetics and Breeding of the Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, Peoples Republic of China. .,The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Peoples Republic of China.
| |
Collapse
|
|
41
|
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
| |
Collapse
|
|
42
|
Akita D, Kano K, Saito-Tamura Y, Mashimo T, Sato-Shionome M, Tsurumachi N, Yamanaka K, Kaneko T, Toriumi T, Arai Y, Tsukimura N, Matsumoto T, Ishigami T, Isokawa K, Honda M. Use of Rat Mature Adipocyte-Derived Dedifferentiated Fat Cells as a Cell Source for Periodontal Tissue Regeneration. Front Physiol 2016; 7:50. [PMID: 26941649 PMCID: PMC4763019 DOI: 10.3389/fphys.2016.00050] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2015] [Accepted: 02/02/2016] [Indexed: 12/25/2022] Open
Abstract
Lipid-free fibroblast-like cells, known as dedifferentiated fat (DFAT) cells, can be generated from mature adipocytes with a large single lipid droplet. DFAT cells can re-establish their active proliferation ability and can transdifferentiate into various cell types under appropriate culture conditions. The first objective of this study was to compare the multilineage differentiation potential of DFAT cells with that of adipose-derived stem cells (ASCs) on mesenchymal stem cells. We obtained DFAT cells and ASCs from inbred rats and found that rat DFAT cells possess higher osteogenic differentiation potential than rat ASCs. On the other hand, DFAT cells show similar adipogenic differentiation, and chondrogenic differentiation potential in comparison with ASCs. The second objective of this study was to assess the regenerative potential of DFAT cells combined with novel solid scaffolds composed of PLGA (Poly d, l-lactic-co-glycolic acid) on periodontal tissue, and to compare this with the regenerative potential of ASCs combined with PLGA scaffolds. Cultured DFAT cells and ASCs were seeded onto PLGA scaffolds (DFAT/PLGA and ASCs/PLGA) and transplanted into periodontal fenestration defects in rat mandible. Micro computed tomography analysis revealed a significantly higher amount of bone regeneration in the DFAT/PLGA group compared with that of ASCs/PLGA and PLGA-alone groups at 2, 3, and 5 weeks after transplantation. Similarly, histomorphometric analysis showed that DFAT/PLGA groups had significantly greater width of cementum, periodontal ligament and alveolar bone than ASCs/PLGA and PLGA-alone groups. In addition, transplanted fluorescent-labeled DFAT cells were observed in the periodontal ligament beside the newly formed bone and cementum. These findings suggest that DFAT cells have a greater potential for enhancing periodontal tissue regeneration than ASCs. Therefore, DFAT cells are a promising cell source for periodontium regeneration.
Collapse
Affiliation(s)
- Daisuke Akita
- Department of Partial Denture Prosthodontics, School of Dentistry, Nihon University Tokyo, Japan
| | - Koichiro Kano
- Laboratory of Cell and Tissue Biology, College of Bioresource Science, Nihon University Fujisawa, Japan
| | - Yoko Saito-Tamura
- Department of Orthodontics, School of Dentistry, Nihon University Tokyo, Japan
| | - Takayuki Mashimo
- Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Juntendo University Tokyo, Japan
| | - Momoko Sato-Shionome
- Department of Pediatric Dentistry, School of Dentistry, Nihon University Tokyo, Japan
| | - Niina Tsurumachi
- Department of Orthodontics, School of Dentistry, Nihon University Tokyo, Japan
| | | | | | - Taku Toriumi
- Department of Anatomy, School of Dentistry, Nihon University Tokyo, Japan
| | | | - Naoki Tsukimura
- Department of Partial Denture Prosthodontics, School of Dentistry, Nihon University Tokyo, Japan
| | - Taro Matsumoto
- Division of Cell Regeneration and Transplantation, Department of Functional Morphology, School of Medicine, Nihon University Tokyo, Japan
| | - Tomohiko Ishigami
- Department of Partial Denture Prosthodontics, School of Dentistry, Nihon University Tokyo, Japan
| | - Keitaro Isokawa
- Department of Anatomy, School of Dentistry, Nihon University Tokyo, Japan
| | - Masaki Honda
- Department of Oral Anatomy, School of Dentistry, Aichi-Gakuin University Nagoya, Japan
| |
Collapse
|
|
43
|
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.
Collapse
|
|
44
|
Application of Green Tea Catechin for Inducing the Osteogenic Differentiation of Human Dedifferentiated Fat Cells in Vitro. Int J Mol Sci 2015; 16:27988-8000. [PMID: 26602917 PMCID: PMC4691028 DOI: 10.3390/ijms161226081] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Revised: 11/16/2015] [Accepted: 11/18/2015] [Indexed: 12/21/2022] Open
Abstract
Despite advances in stem cell biology, there are few effective techniques to promote the osteogenic differentiation of human primary dedifferentiated fat (DFAT) cells. We attempted to investigate whether epigallocatechin-3-gallate (EGCG), the main component of green tea catechin, facilitates early osteogenic differentiation and mineralization on DFAT cells in vitro. DFAT cells were treated with EGCG (1.25-10 μM) in osteogenic medium (OM) with or without 100 nM dexamethasone (Dex) for 12 days (hereafter two osteogenic media were designated as OM(Dex) and OM). Supplementation of 1.25 μM EGCG to both the media effectively increased the mRNA expression of collagen 1 (COL1A1) and runt-related transcription factor 2 (RUNX2) and also increased proliferation and mineralization. Compared to OM(Dex) with EGCG, OM with EGCG induced earlier expression for COL1A1 and RUNX2 at day 1 and higher mineralization level at day 12. OM(Dex) with 10 μM EGCG remarkably hampered the proliferation of the DFAT cells. These results suggest that OM(without Dex) with EGCG might be a preferable medium to promote proliferation and to induce osteoblast differentiation of DFAT cells. Our findings provide an insight for the combinatory use of EGCG and DFAT cells for bone regeneration and stem cell-based therapy.
Collapse
|
|
45
|
Phenotypic and Functional Properties of Porcine Dedifferentiated Fat Cells during the Long-Term Culture In Vitro. BIOMED RESEARCH INTERNATIONAL 2015; 2015:673651. [PMID: 26090433 PMCID: PMC4450286 DOI: 10.1155/2015/673651] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Revised: 04/25/2015] [Accepted: 04/30/2015] [Indexed: 12/11/2022]
Abstract
It has been proved that terminally differentiated mature adipocytes possess abilities to dedifferentiate into fibroblast-like progeny cells with self-renewal and multiple differentiation, termed dedifferentiated fat (DFAT) cells. However, the biological properties of DFAT cells during long-term culture in vitro have not been elucidated. Here, we obtained fibroblast-like morphology of porcine DFAT cells by ceiling culture. During the dedifferentiation process, round mature adipocytes with single large lipid droplets changed into spindle-shaped cells accompanied by the adipogenic markers PPARγ, aP2, LPL, and Adiponectin significant downregulation. Flow cytometric analysis showed that porcine DFAT cells displayed similar cell-surface antigen profile to mesenchymal stem cells (MSCs). Furthermore, different passages of porcine DFAT cells during long-term culture in vitro retained high levels of cell viabilities (>97%), efficient proliferative capacity including population doubling time ranged from 20 h to 22 h and population doubling reached 47.40 ± 1.64 by 58 days of culture. In addition, porcine DFAT cells maintained the multiple differentiation capabilities into adipocytes, osteoblasts, and skeletal myocytes and displayed normal chromosomal karyotypes for prolonged passaging. Therefore, porcine DFAT cells may be a novel model of stem cells for studying the functions of gene in the different biological events.
Collapse
|
|
46
|
Okita N, Honda Y, Kishimoto N, Liao W, Azumi E, Hashimoto Y, Matsumoto N. Supplementation of Strontium to a Chondrogenic Medium Promotes Chondrogenic Differentiation of Human Dedifferentiated Fat Cells. Tissue Eng Part A 2015; 21:1695-704. [DOI: 10.1089/ten.tea.2014.0282] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Affiliation(s)
- Naoya Okita
- Department of Orthodontics, Osaka Dental University, Osaka, Japan
| | - Yoshitomo Honda
- Institute of Dental Research, Osaka Dental University, Osaka, Japan
| | | | - Wen Liao
- Department of Orthodontics, Osaka Dental University, Osaka, Japan
| | - Eiko Azumi
- Department of Orthodontics, Osaka Dental University, Osaka, Japan
| | | | | |
Collapse
|
|
47
|
Maruyama T, Fukuda N, Matsumoto T, Kano K, Endo M, Kazama M, Kazama T, Ikeda J, Matsuda H, Ueno T, Abe M, Okada K, Soma M, Matsumoto K, Kawachi H. Systematic implantation of dedifferentiated fat cells ameliorated monoclonal antibody 1-22-3-induced glomerulonephritis by immunosuppression with increases in TNF-stimulated gene 6. Stem Cell Res Ther 2015; 6:80. [PMID: 25889917 PMCID: PMC4455708 DOI: 10.1186/s13287-015-0069-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2014] [Revised: 02/15/2015] [Accepted: 03/27/2015] [Indexed: 02/28/2023] Open
Abstract
INTRODUCTION Implantation of mesenchymal stem cells (MSCs) has recently been reported to repair tissue injuries through anti-inflammatory and immunosuppressive effects. We established dedifferentiated fat (DFAT) cells that show identical characteristics to MSCs. METHODS We examined the effects of 10(6) of DFAT cells infused through renal artery or tail vein on monoclonal antibody (mAb) 1-22-3-induced glomerulonephritis (as an immunological type of renal injury) and adriamycin-induced nephropathy (as a non-immunological type of renal injury) in rats. The mAb 1-22-3-injected rats were also implanted with 10(6) of DFAT cells transfected with TSG-6 siRNA through tail vein. RESULTS Although DFAT cells transfused into blood circulation through the tail vein were trapped mainly in lungs without reaching the kidneys, implantation of DFAT cells reduced proteinuria and improved glomerulosclerosis and interstitial fibrosis. Implantation of DFAT cells through the tail vein significantly decreased expression of kidney injury molecule-1, collagen IV and fibronectin mRNAs, whereas nephrin mRNA expression was increased. Implantation of DFAT cells did not improve adriamycin-induced nephropathy, but significantly decreased the glomerular influx of macrophages, common leukocytes and pan T cells. However, the glomerular influx of helper T cells, was increased. Implantation of DFAT cells decreased expression of interleukin (IL)-6 and IL-12β mRNAs and increased expression of TNF-stimulated gene (TSG)-6 mRNA in renal cortex from mAb 1-22-3-injected rats. The basal level of TSG-6 protein was significantly higher in DFAT cells than in fibroblasts. Expression of TSG-6 mRNA in MCs cocultured with DFAT cells was significantly higher than in mesangial cells or DFAT cells alone. Systematic implantation of DFAT cells with TSG-6 siRNA through tail vein did not improve proteinuria, renal dysfunction and renal degeneration in the mAb 1-22-3-injected rats. CONCLUSION Systematic implantation of DFAT cells effectively ameliorated mAb 1-22-3-induced glomerulonephritis through immunosuppressive effects accompanied by the suppression of macrophage infiltration and expression of IL-6, IL-10 and IL-12β, and increased production of serum and renal TSG-6 that improved the mAb 1-22-3-induced renal degeneration by the immunosuppressive effects of TSG-6. Thus DFAT cells will be suitable cell source for the treatment of immunological progressive renal diseases.
Collapse
Affiliation(s)
- Takashi Maruyama
- Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
| | - Noboru Fukuda
- Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. .,Advanced Research Institute of the Sciences and Humanities, Nihon University Graduate School, Tokyo, Japan.
| | - Taro Matsumoto
- Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan.
| | - Koichiro Kano
- Laboratory of Cell and Tissue Biology, College of Bioresource Science, Nihon University, Fujisawa, Japan.
| | - Morito Endo
- Faculty of Human Health Science, Hachinohe Gakuin University, Hachinohe, Aomori, Japan.
| | - Minako Kazama
- Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan.
| | - Tomohiko Kazama
- Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan.
| | - Jin Ikeda
- Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
| | - Hiroyuki Matsuda
- Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
| | - Takahiro Ueno
- Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
| | - Masanori Abe
- Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
| | - Kazuyoshi Okada
- Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
| | - Masayoshi Soma
- Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
| | - Koichi Matsumoto
- Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
| | - Hiroshi Kawachi
- Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| |
Collapse
|
|
48
|
Hu X, Luo P, Peng X, Song T, Zhou Y, Wei H, Peng J, Jiang S. Molecular cloning, expression pattern analysis of porcine Rb1 gene and its regulatory roles during primary dedifferentiated fat cells adipogenic differentiation. Gen Comp Endocrinol 2015; 214:77-86. [PMID: 25626122 DOI: 10.1016/j.ygcen.2015.01.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Revised: 01/13/2015] [Accepted: 01/19/2015] [Indexed: 11/19/2022]
Abstract
Adipocytes are the main constituent of adipose tissue and are considered to be a corner stone in the homeostatic control of whole body metabolism. Recent reports evidenced that retinoblastoma 1 (Rb1) gene plays an important role in fat development and adipogenesis in mice. Here, we cloned the partial cDNA sequences of the porcine Rb1 gene which contains the complete coding sequences (CDS) of 2820bp encoding a protein of 939 amino acids. Bioinformatic analysis revealed that the CDS of porcine Rb1 was highly identical with those of cattle, human and mice. The porcine Rb1 has three typical conserved structural domains, including Rb-A pocket domain, CYCLIN domain and C-terminus domain, and the phylogenetic tree indicates a closer genetic relationship with cattle and human. Tissue distribution analysis showed that Rb1 expression appeared to be ubiquitously in various tissues, being higher in heart, liver, muscle, and stomach. Furthermore, significant downregulation of Rb1 was found at the initial stage of dedifferentiated fat (DFAT) cells adipogenic differentiation. With the knockdown of the Rb1 expression by siRNA, the number of DFAT cells recruited to white rather than brown adipogenesis was promoted, and mRNA levels of adipogenic markers, such as PPARγ, aP2, LPL and adiponectin and protein expression of PPARγ and adiponectin were increased after hormone stimulation. The underlying mechanisms may be that knockdown of Rb1 promotes the mitotic clonal expansion and PPARγ expression by derepressing the transcriptional activity of E2F so as to facilitate the first steps of adipogenesis. In summary, we cloned and characterized an important negative regulator in adipogenic commitment of porcine DFAT cells.
Collapse
Affiliation(s)
- Xiaoming Hu
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, People's Republic of China
| | - Pei Luo
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Xuewu Peng
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Tongxing Song
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Yuanfei Zhou
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Hongkui Wei
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China
| | - Jian Peng
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, People's Republic of China.
| | - Siwen Jiang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China; Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, People's Republic of China.
| |
Collapse
|
|
49
|
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.
Collapse
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
| |
Collapse
|
|
50
|
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]
|