|
1
|
Waters JA, Robinson M, Lujano-Olazaba O, Lucht C, Gilbert SF, House CD. Omental preadipocytes stimulate matrix remodeling and IGF signaling to support ovarian cancer metastasis. Cancer Res 2024; 84:743101. [PMID: 38635891 PMCID: PMC11217736 DOI: 10.1158/0008-5472.can-23-2613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 01/19/2024] [Accepted: 04/03/2024] [Indexed: 04/20/2024]
Abstract
Ovarian cancer can metastasize to the omentum, which is associated with a complex tumor microenvironment. Omental stromal cells facilitate ovarian cancer colonization by secreting cytokines and growth factors. Improved understanding of the tumor supportive functions of specific cell populations in the omentum could identify strategies to prevent and treat ovarian cancer metastasis. Here, we showed that omental preadipocytes enhance the tumor initiation capacity of ovarian cancer cells. Secreted factors from preadipocytes supported cancer cell viability during nutrient and isolation stress and enabled prolonged proliferation. Co-culturing with pre-adipocytes led to upregulation of genes involved in extracellular matrix (ECM) organization, cellular response to stress, and regulation of insulin-like growth factor (IGF) signaling in ovarian cancer cells. IGF-1 induced ECM genes and increased alternative NF-κB signaling by activating RelB. Inhibiting the IGF-1 receptor (IGF1R) initially increased tumor omental adhesion but decreased growth of established preadipocyte-induced subcutaneous tumors as well as established intraperitoneal tumors. Together, this study shows that omental preadipocytes support ovarian cancer progression, which has implications for targeting metastasis.
Collapse
Affiliation(s)
- Jennifer A. Waters
- Department of Biology, San Diego State University, San Diego, California.
| | - Mikella Robinson
- Department of Biology, San Diego State University, San Diego, California.
| | | | - Cassidy Lucht
- Department of Biology, San Diego State University, San Diego, California.
| | - Samuel F. Gilbert
- Department of Biology, San Diego State University, San Diego, California.
| | - Carrie D. House
- Department of Biology, San Diego State University, San Diego, California.
- Moores Cancer Center, University of California San Diego, La Jolla, California.
| |
Collapse
|
|
2
|
Arderiu G, Civit-Urgell A, Díez-Caballero A, Moscatiello F, Ballesta C, Badimon L. Differentiation of Adipose Tissue Mesenchymal Stem Cells into Endothelial Cells Depends on Fat Depot Conditions: Regulation by miRNA. Cells 2024; 13:513. [PMID: 38534357 PMCID: PMC10969675 DOI: 10.3390/cells13060513] [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: 02/05/2024] [Revised: 03/08/2024] [Accepted: 03/11/2024] [Indexed: 03/28/2024] Open
Abstract
The development of obesity is associated with substantial modulation of adipose tissue (AT) structure. The plasticity of the AT is reflected by its remarkable ability to expand or reduce in size throughout the adult lifespan, which is linked to the development of its vasculature. This increase in AT vasculature could be mediated by the differentiation of adipose tissue-derived stem cells (ASCs) into endothelial cells (ECs) and form new microvasculature. We have already shown that microRNA (miRNA)-145 regulates the differentiation of ASCs into EC-like (ECL) cells. Here, we investigated whether ASCs-differentiation into ECs is governed by a miRNAs signature that depends on fat depot location and /or the metabolic condition produced by obesity. Human ASCs, which were obtained from white AT by surgical procedures from lean and obese patients, were induced to differentiate into ECL cells. We have identified that miRNA-29b-3p in both subcutaneous (s)ASCs and visceral ASCs and miRNA-424-5p and miRNA-378a-3p in subcutaneous (s)ASCs are involved in differentiation into EC-like cells. These miRNAs modulate their pro-angiogenic effects on ASCs by targeting FGFR1, NRP2, MAPK1, and TGF-β2, and the MAPK signaling pathway. We show for the first time that miRNA-29b-3p upregulation contributes to ASCs' differentiation into ECL cells by directly targeting TGFB2 in both sASCs and visceral ASCs. Moreover, our results reveal that, independent of sASCs' origin (obese/lean), the upregulation of miRNA-378a-3p and the downregulation of miRNA-424-5p inhibit MAPK1 and overexpress FGFR1 and NRP2, respectively. In summary, both the adipose depot location and obesity affect the differentiation of resident ASCs through the expression of specific miRNAs.
Collapse
Affiliation(s)
- Gemma Arderiu
- Cardiovascular-Program, Institut de Recerca Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain; (A.C.-U.); (L.B.)
- Ciber CV, Instituto Carlos III, 28029 Madrid, Spain
| | - Anna Civit-Urgell
- Cardiovascular-Program, Institut de Recerca Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain; (A.C.-U.); (L.B.)
- Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain
| | - Alberto Díez-Caballero
- Centro Médico Teknon, Grupo Quiron Salut, 08022 Barcelona, Spain; (A.D.-C.); (F.M.); (C.B.)
| | - Fabrizio Moscatiello
- Centro Médico Teknon, Grupo Quiron Salut, 08022 Barcelona, Spain; (A.D.-C.); (F.M.); (C.B.)
| | - Carlos Ballesta
- Centro Médico Teknon, Grupo Quiron Salut, 08022 Barcelona, Spain; (A.D.-C.); (F.M.); (C.B.)
| | - Lina Badimon
- Cardiovascular-Program, Institut de Recerca Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain; (A.C.-U.); (L.B.)
- Ciber CV, Instituto Carlos III, 28029 Madrid, Spain
| |
Collapse
|
|
3
|
Mikłosz A, Łukaszuk B, Supruniuk E, Grubczak K, Kusaczuk M, Chabowski A. RabGAP AS160/TBC1D4 deficiency increases long-chain fatty acid transport but has little additional effect on obesity and metabolic syndrome in ADMSCs-derived adipocytes of morbidly obese women. Front Mol Biosci 2023; 10:1232159. [PMID: 37602323 PMCID: PMC10435366 DOI: 10.3389/fmolb.2023.1232159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 07/12/2023] [Indexed: 08/22/2023] Open
Abstract
The Akt substrate of 160 kDa (AS160), also known as TBC1 domain family member 4 (TBC1D4), represents a crucial regulator of insulin-stimulated glucose uptake in skeletal muscle and adipose tissue. Recent evidence suggests that AS160/TBC1D4 may also control the cellular entry of long-chain fatty acids (LCFAs), resulting in changes to the lipid profile of muscles and fat cells in lean subjects. However, there are virtually no data on AS160/TBC1D4 expression and its modulatory role in lipid metabolism in the adipocytes from morbidly obese individuals of different metabolic status. In this study, we evaluated the effect of the three main factors, i.e., AS160 silencing, obesity, and metabolic syndrome on lipid uptake and profile in fully differentiated adipocytes derived from mesenchymal stem cells (ADMSCs) of lean and obese (with/without metabolic syndrome) postmenopausal women. Additionally, we tested possible interactions between the explanatory variables. In general, obesity translated into a greater content of fatty acid transporters (especially CD36/SR-B2 and SLC27A4/FATP4) and boosted accumulation of all the examined lipid fractions, i.e., triacylglycerols (TAGs), diacylglycerols (DAGs), and free fatty acids (FFAs). The aforementioned were further enhanced by metabolic syndrome. Moreover, AS160 deficiency also increased the abundance of SLC27A4/FATP4 and CD36/SR-B2, especially on the cell surface of the adipocytes derived from ADMSCs of subcutaneous deposit. This was further accompanied by increased LCFA (palmitic acid) uptake. Despite the aforementioned, AS160 silencing seemed unable to significantly affect the phenotype of the adipocytes stemming from obese patients with respect to their cellular lipid profile as we observed virtually no changes in TAG, DAG, and FFA contents when compared to cells with the reference level of proteins. Nevertheless, knockdown of AS160 stimulated fatty acid oxidation, which may indicate that adaptive mechanisms counteract excessive lipid accumulation. At the same time, adipocytes of visceral origin were rather insensitive to the applied intervention.
Collapse
Affiliation(s)
- Agnieszka Mikłosz
- Department of Physiology, Medical University of Bialystok, Bialystok, Poland
| | - Bartłomiej Łukaszuk
- Department of Physiology, Medical University of Bialystok, Bialystok, Poland
| | - Elżbieta Supruniuk
- Department of Physiology, Medical University of Bialystok, Bialystok, Poland
| | - Kamil Grubczak
- Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland
| | - Magdalena Kusaczuk
- Department of Pharmaceutical Biochemistry, Medical University of Bialystok, Bialystok, Poland
| | - Adrian Chabowski
- Department of Physiology, Medical University of Bialystok, Bialystok, Poland
| |
Collapse
|
|
4
|
Song Q, Liu S, Wang J, Chai J, Wen J, Xu C. Hypoxia promotes white adipose tissues browning in rats under simulated environment at altitude of 5000 m. Biochem Biophys Res Commun 2023; 666:146-153. [PMID: 37187092 DOI: 10.1016/j.bbrc.2023.05.015] [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: 04/09/2023] [Revised: 04/24/2023] [Accepted: 05/03/2023] [Indexed: 05/17/2023]
Abstract
People living in plains tend to decrease in body weight or body fat percentage after entering the plateau. Previous studies have found that plateau animals can burn fat and release calories through white adipose tissues (WATs) browning. However, these studies have focused on the effect of cold stimulation that induced WATs browning while there's hardly study on the effect of hypoxia. In this study, we investigate that whether and how hypoxia contributes to WATs browning in rats from acute to chronic hypoxia. We constructed hypobaric hypoxic rat models by exposing 9-week-old male SD rats to a hypobaric hypoxic chamber for 1, 3, 14 and 28 days (Group H) under simulated environment at altitude of 5000 m. We also established normoxic control groups for each time period (Group C), as well as paired 1-day and 14-day normoxic food-restriction rats that were fed the same amount of food as the hypoxic group ate (Group R). We then observed the growth status of rats and recorded dynamic changes in histologic, cellular and molecular levels of perirenal WATs (PWAT), epididymal WATs (EWAT) and subcutaneous WATs (SWAT) in each group. Results showed that (1) Hypoxic rats had lower food intake, significantly lower body weight than control rats, and showed lower WATs index. (2) In group H14, ASC1 mRNA expressions of PWAT and EWAT in rats were lower than that in group C14, and PAT2 mRNA expression of EWAT was higher than that in both group C14 and R14. In group R14, however, ASC1 mRNA expressions of PWAT and EWAT in rats were higher than both group C14 and H14, and that of SWAT was also significantly higher than group C14. (3) In group H3, both the mRNA and protein levels of uncoupling protein 1 (UCP1) of PWAT in rats were significantly increased than group C3. And in group H14, those of EWAT in rats were significantly increased than group C14. (4) In plasma of rats, norepinephrine (NE) level was significantly increased in group H3 than group C3, and free fatty acids (FFAs) level was significantly increased in group H14 than both group C14 and R14. In group R1, FASN mRNA expressions of PWAT and EWAT in rats were down-regulated than group C1. In group H3, FASN mRNA expressions of PWAT and EWAT in rats were down-regulated while ATGL mRNA expression of EWAT was up-regulated than group C3. Conversely, in group R14, FASN mRNA expressions of PWAT and EWAT in rats were significantly up-regulated than group C14 and H14. These results suggested that hypoxia promoted different WATs browning in rats under simulated environment at altitude of 5000 m and changed the lipid metabolism in WATs. Furthermore, rats in the chronic hypoxic group showed a completely different lipid metabolism of WATs from that in paired food-restriction group.
Collapse
Affiliation(s)
- Qiaoyue Song
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China
| | - Shiying Liu
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China
| | - Jianan Wang
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China
| | - Jiamin Chai
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China
| | - Jigang Wen
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China
| | - Chengli Xu
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China.
| |
Collapse
|
|
5
|
Georgiev-Hristov T, García-Arranz M, Trébol-López J, Barba-Recreo P, García-Olmo D. Searching for the Optimal Donor for Allogenic Adipose-Derived Stem Cells: A Comprehensive Review. Pharmaceutics 2022; 14:2338. [PMID: 36365156 PMCID: PMC9696054 DOI: 10.3390/pharmaceutics14112338] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 08/22/2022] [Accepted: 10/27/2022] [Indexed: 11/15/2023] Open
Abstract
Adipose-derived stem cells comprise several clinically beneficial qualities that have been explored in basic research and have motivated several clinical studies with promising results. After being approved in the European Union, UK, Switzerland, Israel, and Japan, allogeneic adipose-derived stem cells (darvadstrocel) have been recently granted a regenerative medicine advanced therapy (RMAT) designation by US FDA for complex perianal fistulas in adults with Crohn's disease. This huge scientific step is likely to impact the future spread of the indications of allogeneic adipose-derived stem cell applications. The current knowledge on adipose stem cell harvest describes quantitative and qualitative differences that could be influenced by different donor conditions and donor sites. In this comprehensive review, we summarize the current knowledge on the topic and propose donor profiles that could provide the optimal initial quality of this living drug, as a starting point for further applications and studies in different pathological conditions.
Collapse
Affiliation(s)
- Tihomir Georgiev-Hristov
- Servicio de Cirugía General y del Aparato Digestivo, Hospital General Universitario de Villalba, 28400 Madrid, Spain
- Facultad de Medicina, Universidad Alfonso X, 28691 Madrid, Spain
| | - Mariano García-Arranz
- Instituto de Investigación Sanitaria, Hospital Universitario Fundación Jiménez Díaz, 28040 Madrid, Spain
- Departamento de Cirugía, Universidad Autónoma de Madrid, 28029 Madrid, Spain
| | - Jacobo Trébol-López
- Servicio de Cirugía General y del Aparato Digestivo, Complejo Asistencial Universitario de Salamanca, 37007 Salamanca, Spain
| | - Paula Barba-Recreo
- Facultad de Medicina, Universidad Alfonso X, 28691 Madrid, Spain
- Servicio de Cirugía Maxilofacial, Hospital Universitario Rey Juan Carlos, 28933 Madrid, Spain
| | - Damián García-Olmo
- Instituto de Investigación Sanitaria, Hospital Universitario Fundación Jiménez Díaz, 28040 Madrid, Spain
- Departamento de Cirugía, Universidad Autónoma de Madrid, 28029 Madrid, Spain
| |
Collapse
|
|
6
|
Ishaq A, Tchkonia T, Kirkland JL, Siervo M, Saretzki G. Palmitate induces DNA damage and senescence in human adipocytes in vitro that can be alleviated by oleic acid but not inorganic nitrate. Exp Gerontol 2022; 163:111798. [PMID: 35390489 PMCID: PMC9214712 DOI: 10.1016/j.exger.2022.111798] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 03/28/2022] [Accepted: 03/31/2022] [Indexed: 11/22/2022]
Abstract
Hypertrophy in white adipose tissue (WAT) can result in sustained systemic inflammation, hyperlipidaemia, insulin resistance, and onset of senescence in adipocytes. Inflammation and hypertrophy can be induced in vitro using palmitic acid (PA). WAT adipocytes have innately low β-oxidation capacity, while inorganic nitrate can promote a beiging phenotype, with promotion of β-oxidation when cells are exposed to nitrate during differentiation. We hypothesized that treatment of human adipocytes with PA in vitro can induce senescence, which might be attenuated by nitrate treatment through stimulation of β-oxidation to remove accumulated lipids. Differentiated subcutaneous and omental adipocytes were treated with PA and nitrate and senescence markers were analyzed. PA induced DNA damage and increased p16INK4a levels in both human subcutaneous and omental adipocytes in vitro. However, lipid accumulation and lipid droplet size increased after PA treatment only in subcutaneous adipocytes. Thus, hypertrophy and senescence seem not to be causally associated. Contrary to our expectations, subsequent treatment of PA-induced adipocytes with nitrate did not attenuate PA-induced lipid accumulation or senescence. Instead, we found a significantly beneficial effect of oleic acid (OA) on human subcutaneous adipocytes when applied together with PA, which reduced the DNA damage caused by PA treatment.
Collapse
Affiliation(s)
- Abbas Ishaq
- Biosciences Institute, Campus for Ageing and Vitality, Newcastle upon Tyne, UK
| | - Tamara Tchkonia
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, United States of America
| | - James L Kirkland
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, United States of America
| | - Mario Siervo
- Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK; School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK
| | - Gabriele Saretzki
- Biosciences Institute, Campus for Ageing and Vitality, Newcastle upon Tyne, UK.
| |
Collapse
|
|
7
|
Mikłosz A, Łukaszuk B, Supruniuk E, Grubczak K, Starosz A, Kusaczuk M, Naumowicz M, Chabowski A. The Phenotype of the Adipocytes Derived from Subcutaneous and Visceral ADMSCs Is Altered When They Originate from Morbidly Obese Women: Is There a Memory Effect? Cells 2022; 11:1435. [PMID: 35563741 PMCID: PMC9099624 DOI: 10.3390/cells11091435] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 04/19/2022] [Accepted: 04/21/2022] [Indexed: 11/17/2022] Open
Abstract
Adipose tissue is an abundant source of mesenchymal stem cells (ADMSCs). Evidence has suggested that depot-specific ADMSCs (obtained from subcutaneous or visceral adipose tissue-subADMSCs or visADMSCs, respectively) account for differential responses of each depot to metabolic challenges. However, little is known about the phenotype and changes in metabolism of the adipocytes derived from ADMSCs of obese individuals. Therefore, we investigated the phenotypic and metabolic characteristics, particularly the lipid profile, of fully differentiated adipocytes derived from ADMSCs of lean and obese (with/without metabolic syndrome) postmenopausal women. We observed a depot-specific pattern, with more pronounced changes present in the adipocytes obtained from subADMSCs. Namely, chronic oversupply of fatty acids (present in morbid obesity) triggered an increase in CD36/SR-B2 and FATP4 protein content (total and cell surface), which translated to an increased LCFA influx (3H-palmitate uptake). This was associated with the accumulation of TAG and DAG in these cells. Furthermore, we observed that the adipocytes of visADMSCs origin were larger and showed smaller granularity than their counterparts of subADMSCs descent. Although ADMSCs were cultured in vitro, in a fatty acids-deprived environment, obesity significantly influenced the functionality of the progenitor adipocytes, suggesting the existence of a memory effect.
Collapse
Affiliation(s)
- Agnieszka Mikłosz
- Department of Physiology, Medical University of Bialystok, Mickiewicza 2C Street, 15-222 Bialystok, Poland; (B.Ł.); (E.S.); (A.C.)
| | - Bartłomiej Łukaszuk
- Department of Physiology, Medical University of Bialystok, Mickiewicza 2C Street, 15-222 Bialystok, Poland; (B.Ł.); (E.S.); (A.C.)
| | - Elżbieta Supruniuk
- Department of Physiology, Medical University of Bialystok, Mickiewicza 2C Street, 15-222 Bialystok, Poland; (B.Ł.); (E.S.); (A.C.)
| | - Kamil Grubczak
- Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Waszyngtona 13 Street, 15-269 Bialystok, Poland; (K.G.); (A.S.)
| | - Aleksandra Starosz
- Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Waszyngtona 13 Street, 15-269 Bialystok, Poland; (K.G.); (A.S.)
| | - Magdalena Kusaczuk
- Department of Pharmaceutical Biochemistry, Medical University of Bialystok, Mickiewicza 2A Street, 15-222 Bialystok, Poland;
| | - Monika Naumowicz
- Department of Physical Chemistry, Faculty of Chemistry, University of Bialystok, K. Ciolkowskiego 1K Street, 15-245 Bialystok, Poland;
| | - Adrian Chabowski
- Department of Physiology, Medical University of Bialystok, Mickiewicza 2C Street, 15-222 Bialystok, Poland; (B.Ł.); (E.S.); (A.C.)
| |
Collapse
|
|
8
|
Zuccarini M, Giuliani P, Di Liberto V, Frinchi M, Caciagli F, Caruso V, Ciccarelli R, Mudò G, Di Iorio P. Adipose Stromal/Stem Cell-Derived Extracellular Vesicles: Potential Next-Generation Anti-Obesity Agents. Int J Mol Sci 2022; 23:ijms23031543. [PMID: 35163472 PMCID: PMC8836090 DOI: 10.3390/ijms23031543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 01/26/2022] [Accepted: 01/26/2022] [Indexed: 02/01/2023] Open
Abstract
Over the last decade, several compounds have been identified for the treatment of obesity. However, due to the complexity of the disease, many pharmacological interventions have raised concerns about their efficacy and safety. Therefore, it is important to discover new factors involved in the induction/progression of obesity. Adipose stromal/stem cells (ASCs), which are mostly isolated from subcutaneous adipose tissue, are the primary cells contributing to the expansion of fat mass. Like other cells, ASCs release nanoparticles known as extracellular vesicles (EVs), which are being actively studied for their potential applications in a variety of diseases. Here, we focused on the importance of the contribution of ASC-derived EVs in the regulation of metabolic processes. In addition, we outlined the advantages/disadvantages of the use of EVs as potential next-generation anti-obesity agents.
Collapse
Affiliation(s)
- Mariachiara Zuccarini
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (M.Z.); (P.G.); (P.D.I.)
- Center for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Via L. Polacchi, 66100 Chieti, Italy;
| | - Patricia Giuliani
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (M.Z.); (P.G.); (P.D.I.)
- Center for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Via L. Polacchi, 66100 Chieti, Italy;
| | - Valentina Di Liberto
- Department of Biomedicine, Neuroscience and Advanced Diagnostic, University of Palermo, 90128 Palermo, Italy; (V.D.L.); (M.F.); (G.M.)
| | - Monica Frinchi
- Department of Biomedicine, Neuroscience and Advanced Diagnostic, University of Palermo, 90128 Palermo, Italy; (V.D.L.); (M.F.); (G.M.)
| | - Francesco Caciagli
- Center for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Via L. Polacchi, 66100 Chieti, Italy;
| | - Vanni Caruso
- School of Pharmacy and Pharmacology, University of Tasmania, Hobart 7001, Australia;
| | - Renata Ciccarelli
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (M.Z.); (P.G.); (P.D.I.)
- Center for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Via L. Polacchi, 66100 Chieti, Italy;
- Stem TeCh Group, Center for Advanced Studies and Technologies (CAST), Via L. Polacchi, 66100 Chieti, Italy
- Correspondence:
| | - Giuseppa Mudò
- Department of Biomedicine, Neuroscience and Advanced Diagnostic, University of Palermo, 90128 Palermo, Italy; (V.D.L.); (M.F.); (G.M.)
| | - Patrizia Di Iorio
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (M.Z.); (P.G.); (P.D.I.)
- Center for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Via L. Polacchi, 66100 Chieti, Italy;
| |
Collapse
|
|
9
|
Abstract
Scar is a common way of healing after tissue injury. The poor scar healing will not only cause dysfunction of tissues and organs but also affect the appearance of the patients’ body surface, which causes the pressure of life and spirit to the patients. However, the formation of scar tissue is an extremely complex process and its mechanism is not fully understood. At present, there is no treatment method to eliminate scars completely. Fibroblasts are the most abundant cells in the dermis, which have the ability to synthesize and remodel extracellular matrix (ECM). Myofibroblasts actively participate in the wound healing process and influence the outcome. Therefore, both of them play important roles in wound healing and scar formation. Adipose tissue-derived stem cells (ADSCs) are pluripotent stem cells that can act on target cells by paracrine. Adipose tissue stem cell-derived exosomes (ADSC-Exos) are important secretory substances of ADSCs. They are nanomembrane vesicles that can transport a variety of cellular components and fuse with target cells. In this review, we will discuss the effects of ADSCs and ADSC-Exos on the behavior of fibroblasts and myofibroblasts during wound healing and scarring stage in combination with recent studies.
Collapse
|
|
10
|
Gong JH, Dong JY, Xie T, Zhao Q, Lu SL. Different therapeutic effects between diabetic and non-diabetic adipose stem cells in diabetic wound healing. J Wound Care 2021; 30:S14-S23. [PMID: 33856928 DOI: 10.12968/jowc.2021.30.sup4.s14] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
OBJECTIVE This study aimed to investigate how adipose tissue-derived stem cells (ASCs) from diabetic and from non-diabetic rats affect wound healing in different microenvironments. METHOD The two types of ASC-rich cells were distinguished by characteristic surface antigen detection. The ASC-rich cells were transplanted into the wounds of diabetic and non-diabetic rats. Wound healing rates were compared and the healing process in the wound margin sections was used to determine how ASC-rich cells affect wound healing in different microenvironments. RESULTS ASC density was decreased in diabetic rats. The generation time of ASC-rich cells from diabetic rats (d-ASC-rich cells) was longer than that of ASC-rich cells from non-diabetic rats. The number of pre-apoptotic cells in the third generation (passage 3) of d-ASC-rich cells was higher than that among the ASC-rich cells from non-diabetic rats. CD31 and CD34 expression was higher in d-ASC-rich cells than in ASC-rich cells from non-diabetic rats, whereas CD44 and CD105 expression was lower than that in ASC-rich cells from non-diabetic rats. Transplantation of ASC-rich cells from non-diabetic rats promoted wound healing in both non-diabetic and diabetic rats. In contrast, d-ASC-rich cells and enriched nuclear cells only promoted wound healing in non-diabetic rats. ASC-rich cell transplantation promoted greater tissue regeneration than d-ASC-rich cell transplantation. CONCLUSION ASC-rich cells promoted wound healing in diabetic and non-diabetic rats. ASC density was lower in the adipose tissue of diabetic rats compared with non-diabetic rats. d-ASC-rich cells did not promote wound healing in diabetic rats, suggesting that caution is warranted regarding the clinical use of diabetic adipose stem cell transplantation for the treatment of diabetic wounds.
Collapse
Affiliation(s)
- Jia-Hong Gong
- Shanghai Burn Institute, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiao-Yun Dong
- Shanghai Burn Institute, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ting Xie
- Shanghai 9th people's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qingnan Zhao
- University of Texas MD Anderson Cancer Center, Houston, Texas 77054, US
| | - Shu-Liang Lu
- Shanghai Burn Institute, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| |
Collapse
|
|
11
|
Ong WK, Chakraborty S, Sugii S. Adipose Tissue: Understanding the Heterogeneity of Stem Cells for Regenerative Medicine. Biomolecules 2021; 11:biom11070918. [PMID: 34206204 PMCID: PMC8301750 DOI: 10.3390/biom11070918] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/17/2021] [Accepted: 06/17/2021] [Indexed: 12/13/2022] Open
Abstract
Adipose-derived stem cells (ASCs) have been increasingly used as a versatile source of mesenchymal stem cells (MSCs) for diverse clinical investigations. However, their applications often become complicated due to heterogeneity arising from various factors. Cellular heterogeneity can occur due to: (i) nomenclature and criteria for definition; (ii) adipose tissue depots (e.g., subcutaneous fat, visceral fat) from which ASCs are isolated; (iii) donor and inter-subject variation (age, body mass index, gender, and disease state); (iv) species difference; and (v) study design (in vivo versus in vitro) and tools used (e.g., antibody isolation and culture conditions). There are also actual differences in resident cell types that exhibit ASC/MSC characteristics. Multilineage-differentiating stress-enduring (Muse) cells and dedifferentiated fat (DFAT) cells have been reported as an alternative or derivative source of ASCs for application in regenerative medicine. In this review, we discuss these factors that contribute to the heterogeneity of human ASCs in detail, and what should be taken into consideration for overcoming challenges associated with such heterogeneity in the clinical use of ASCs. Attempts to understand, define, and standardize cellular heterogeneity are important in supporting therapeutic strategies and regulatory considerations for the use of ASCs.
Collapse
Affiliation(s)
- Wee Kiat Ong
- School of Pharmacy, Monash University Malaysia, Subang Jaya 47500, Selangor, Malaysia
- Correspondence: (W.K.O.); (S.S.)
| | - Smarajit Chakraborty
- Institute of Bioengineering and Bioimaging (IBB), A*STAR, 31 Biopolis Way, Singapore 138669, Singapore;
| | - Shigeki Sugii
- Institute of Bioengineering and Bioimaging (IBB), A*STAR, 31 Biopolis Way, Singapore 138669, Singapore;
- Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore
- Correspondence: (W.K.O.); (S.S.)
| |
Collapse
|
|
12
|
Gui C, Parson J, Meyer GA. Harnessing adipose stem cell diversity in regenerative medicine. APL Bioeng 2021; 5:021501. [PMID: 33834153 PMCID: PMC8018797 DOI: 10.1063/5.0038101] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 02/26/2021] [Indexed: 12/20/2022] Open
Abstract
Since the first isolation of mesenchymal stem cells from lipoaspirate in the early 2000s, adipose tissue has been a darling of regenerative medicine. It is abundant, easy to access, and contains high concentrations of stem cells (ADSCs) exhibiting multipotency, proregenerative paracrine signaling, and immunomodulation-a winning combination for stem cell-based therapeutics. While basic science, preclinical and clinical findings back up the translational potential of ADSCs, the vast majority of these used cells from a single location-subcutaneous abdominal fat. New data highlight incredible diversity in the adipose morphology and function in different anatomical locations or depots. Even in isolation, ADSCs retain a memory of this diversity, suggesting that the optimal adipose source material for ADSC isolation may be application specific. This review discusses our current understanding of the heterogeneity in the adipose organ, how that heterogeneity translates into depot-specific ADSC characteristics, and how atypical ADSC populations might be harnessed for regenerative medicine applications. While our understanding of the breadth of ADSC heterogeneity is still in its infancy, clear trends are emerging for application-specific sourcing to improve regenerative outcomes.
Collapse
Affiliation(s)
- Chang Gui
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri 63110, USA
| | - Jacob Parson
- Program in Physical Therapy, Washington University in St. Louis, St. Louis, Missouri 63110, USA
| | - Gretchen A. Meyer
- Author to whom correspondence should be addressed:. Tel.: (314) 286-1425. Fax: (314) 747-0674
| |
Collapse
|
|
13
|
Al-Ghadban S, Bunnell BA. Adipose Tissue-Derived Stem Cells: Immunomodulatory Effects and Therapeutic Potential. Physiology (Bethesda) 2021; 35:125-133. [PMID: 32027561 DOI: 10.1152/physiol.00021.2019] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Adipose-derived stem cells (ASCs) can self-renew and differentiate along multiple cell lineages. ASCs are also potently anti-inflammatory due to their inherent ability to regulate the immune system by secreting anti-inflammatory cytokines and growth factors that play a crucial role in the pathology of many diseases, including multiple sclerosis, diabetes mellitus, Crohn's, SLE, and graft-versus-host disease. The immunomodulatory effects and mechanisms of action of ASCs on pathological conditions are reviewed here.
Collapse
Affiliation(s)
- Sara Al-Ghadban
- Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana
| | - Bruce A Bunnell
- Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana.,Department of Pharmacology, School of Medicine, Tulane University, New Orleans, Louisiana
| |
Collapse
|
|
14
|
Piceatannol Is Superior to Resveratrol at Suppressing Adipogenesis in Human Visceral Adipose-Derived Stem Cells. PLANTS 2021; 10:plants10020366. [PMID: 33672932 PMCID: PMC7918058 DOI: 10.3390/plants10020366] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 02/07/2021] [Accepted: 02/09/2021] [Indexed: 01/21/2023]
Abstract
Resveratrol (3,4′,5-trans-trihydroxystilbene) and piceatannol (3,3′,4′,5-trans-tetraphydroxystilbene) are major stilbene compounds that are predominantly present in various natural foods, such as berries and fruits. Both phytochemical compounds are consumed as dietary supplements to prevent various metabolic diseases and for their anti-aging properties. Adipose-derived stem cells from human visceral adipose tissue (vASCs) are a useful in vitro model for evaluating their adipogenic effect. Treatment with resveratrol and piceatannol significantly inhibited lipid accumulation in vASCs. Their effective concentrations were 5, 10, and 20 μM for inhibiting adipogenesis of vASCs. Interestingly, despite the similar chemical structures of the two compounds, piceatannol showed a higher anti-adipogenic effect at 20 μM than resveratrol in vASCs. Moreover, the inhibitory capacity of lipid droplet generation was higher for piceatannol at 20 μM than that of resveratrol. Piceatannol significantly attenuated the expression level of adipogenic markers (e.g., CCAAT/enhanced binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), and adipocyte fatty acid binding protein (aP2)) compared to resveratrol at the mRNA and protein levels. These results suggest that piceatannol is a superior anti-adipogenic compound compared to resveratrol in the vASC model of visceral obesity.
Collapse
|
|
15
|
Arderiu G, Lambert C, Ballesta C, Moscatiello F, Vilahur G, Badimon L. Cardiovascular Risk Factors and Differential Transcriptomic Profile of the Subcutaneous and Visceral Adipose Tissue and Their Resident Stem Cells. Cells 2020; 9:cells9102235. [PMID: 33022994 PMCID: PMC7600037 DOI: 10.3390/cells9102235] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 09/22/2020] [Accepted: 09/29/2020] [Indexed: 01/18/2023] Open
Abstract
Background: The increase in the incidence of obesity and obesity-related cardiovascular risk factors (CVRFs) over the last decades has brought attention on adipose tissue (AT) pathobiology. The expansion of AT is associated with the development of new vasculature needed to perfuse the tissue; however, not all fat depots have the same ability to induce angiogenesis that requires recruitment of their own endothelial cells. In this study we have investigated the effect of different CVRFs, on the angiogenic capacity of the subcutaneous (SAT) and visceral (VAT) adipose tissue and on the function of their mesenchymal cell reservoir. Methods: A transcriptomic approach was used to compare the different angiogenic and inflammatory profiles of the subcutaneous and visceral fat depots from individuals with obesity, as well as their resident stem cells (ASCs). Influence of other risk factors on fat composition was also measured. Finally, the microvesicles (MVs) released by ASCs were isolated and their regenerative potential analyzed by molecular and cellular methodologies. Results: Obesity decreases the angiogenic capacity of AT. There are differences between SAT and VAT; from the 21 angiogenic-related genes analyzed, only three were decreased in SAT compared with those decreased in VAT. ASCs isolated from both fat depots showed significant differences; there was a significant up-regulation of the VEGF-pathway on visceral derived ASCs. ASCs release MVs that stimulate endothelial cell migration and angiogenic capacity. Conclusions: In patients with obesity, SAT expresses a greater number of angiogenic molecules than VAT, independent of the presence of other CVRFs.
Collapse
Affiliation(s)
- Gemma Arderiu
- Cardiovascular-Program ICCC, IR-Hospital Santa Creu I Sant Pau, IIB Sant Pau, 08025 Barcelona, Spain; (C.L.); (G.V.)
- Ciber CV, 28029 Madrid, Spain
- Correspondence: (G.A.); (L.B.); Tel.: +34-935565880 (G.A. & L.B.); Fax: +34-935565559 (G.A. & L.B.)
| | - Carmen Lambert
- Cardiovascular-Program ICCC, IR-Hospital Santa Creu I Sant Pau, IIB Sant Pau, 08025 Barcelona, Spain; (C.L.); (G.V.)
| | - Carlos Ballesta
- Centro Médico Teknon, 08025 Barcelona, Spain; (C.B.); (F.M.)
| | | | - Gemma Vilahur
- Cardiovascular-Program ICCC, IR-Hospital Santa Creu I Sant Pau, IIB Sant Pau, 08025 Barcelona, Spain; (C.L.); (G.V.)
- Ciber CV, 28029 Madrid, Spain
| | - Lina Badimon
- Cardiovascular-Program ICCC, IR-Hospital Santa Creu I Sant Pau, IIB Sant Pau, 08025 Barcelona, Spain; (C.L.); (G.V.)
- Ciber CV, 28029 Madrid, Spain
- Cardiovascular Research Chair UAB, 08025 Barcelona, Spain
- Correspondence: (G.A.); (L.B.); Tel.: +34-935565880 (G.A. & L.B.); Fax: +34-935565559 (G.A. & L.B.)
| |
Collapse
|
|
16
|
Sulforaphene Suppresses Adipocyte Differentiation via Induction of Post-Translational Degradation of CCAAT/Enhancer Binding Protein Beta (C/EBPβ). Nutrients 2020; 12:nu12030758. [PMID: 32183002 PMCID: PMC7146557 DOI: 10.3390/nu12030758] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 03/07/2020] [Accepted: 03/10/2020] [Indexed: 01/13/2023] Open
Abstract
Adipocyte differentiation (adipogenesis) is a crucial process that determines the total number and size of mature adipocytes that will develop. In this study, the anti-adipogenic effect of sulforaphene (SFEN), a dietary isothiocyanate (ITC) derived from radish, is investigated both in 3T3-L1 pre-adipocytes and in human adipose tissue-derived stem cells. The results revealed that SFEN significantly inhibit adipogenic cocktail-induced adipocyte differentiation and lipid accumulation at the early stage of adipogenesis. Additionally, the effects are more potent compared to those of other ITCs derived from various cruciferous vegetables. As a related molecular mechanism of action, SFEN promotes the post-translational degradation of CCAAT/enhancer-binding protein (C/EBP) β by decreasing the stability of C/EBPβ, which is responsible for decreasing the expression of master regulatory proteins such as peroxisome proliferator-activated receptor γ and C/EBPα. Collectively, these results suggest that the intake of SFEN-enriched natural materials could be helpful as a strategy for preventing obesity.
Collapse
|
|
17
|
Park IS, Kim B, Han Y, Yang H, Cho U, Kim SI, Kim JH, Yoon Park JH, Lee KW, Song YS. Decursin and Decursinol Angelate Suppress Adipogenesis through Activation of β-catenin Signaling Pathway in Human Visceral Adipose-Derived Stem Cells. Nutrients 2019; 12:13. [PMID: 31861646 PMCID: PMC7020042 DOI: 10.3390/nu12010013] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 12/17/2019] [Accepted: 12/18/2019] [Indexed: 12/14/2022] Open
Abstract
Visceral adiposity is closely associated with metabolic disorders and cardiovascular diseases. Angelica gigas Nakai (AGN) has been reported to possess anti-obesity effects and higher amounts of coumarin compounds are present in AGN. However, the active compounds suppressing adipogenesis in AGN and mechanisms of action have not been investigated in adipose-derived stem cells (ASCs) isolated from visceral adipose tissue (VAT). Among four coumarin compounds of AGN, decursin (D) and decursinol angelate (DA) significantly inhibited adipocyte differentiation from ASCs. D and DA downregulated CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), adipocyte fatty acid binding protein (aP2), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) at both mRNA and protein levels. Next, treatment with adipogenic differentiation medium (ADM) on ASCs downregulated β-catenin expression at protein level, while addition of D and DA could restore protein expression and nuclear translocation of β-catenin suppressed by ADM. D and DA treatment on ADM treated ASCs increased inhibitory phosphorylation of Glycogen synthase kinase (GSK)-3β, thereby preventing β-catenin from degradation. Additionally, si-β-catenin transfection significantly upregulated protein expression of C/EBPα and PPARγ, alleviating the anti-adipogenic effect of D and DA on ADM treated ASCs. Overall, D and DA, active compounds from AGN, suppressed adipogenesis through activation of β-catenin signaling pathway in ASCs derived from human VAT, possibly using as natural anti-visceral adiposity agents.
Collapse
Affiliation(s)
- In Sil Park
- Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea; (I.S.P.); (H.Y.)
- Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (B.K.); (Y.H.)
| | - Boyun Kim
- Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (B.K.); (Y.H.)
- Department of Anesthesiology, McGovern Medical School, The University of Texas Health Science Center, Houston, TX 77030, USA
| | - Youngjin Han
- Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (B.K.); (Y.H.)
- Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea
| | - Hee Yang
- Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea; (I.S.P.); (H.Y.)
| | - Untack Cho
- Interdisciplinary Program in Cancer Biology, Seoul National University, Seoul 03080, Korea;
| | - Se Ik Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Korea;
| | - Jong Hun Kim
- Department of Food Science and Biotechnology, Sungshin Women’s University, Seoul 01133, Korea;
| | - Jung Han Yoon Park
- Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea;
- Advanced Institutes of Convergence Technology, Seoul National University, Suwon 16229, Korea
| | - Ki Won Lee
- Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea; (I.S.P.); (H.Y.)
- Advanced Institutes of Convergence Technology, Seoul National University, Suwon 16229, Korea
| | - Yong Sang Song
- Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (B.K.); (Y.H.)
- Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Korea;
| |
Collapse
|
|
18
|
Kolodziej M, Strauss S, Lazaridis A, Bucan V, Kuhbier JW, Vogt PM, Könneker S. Influence of glucose and insulin in human adipogenic differentiation models with adipose-derived stem cells. Adipocyte 2019; 8:254-264. [PMID: 31280651 PMCID: PMC6768274 DOI: 10.1080/21623945.2019.1636626] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Autologous fat grafting represents an attractive source for tissue engineering applications in the field of reconstructive medicine. However, in adipogenic differentiation protocols for human adipose-derived stem cells, the concentration of glucose and insulin varies considerably. With the intent to gain maximum tissue augmentation, we focused on the late phase of adipogenesis. In this study, we modified the differentiation protocol for adipose-derived stem cells by prolongation of the induction period and the application highly concentrated glucose and insulin. Human adipose-derived stem cells were isolated from subcutaneous depots and differentiated in a standard induction medium for the first two weeks, followed by two weeks with varying glucose and insulin concentrations. Morphological changes assessed using Oil-Red-O staining were examined for corresponding alterations in the expression of the adipogenic markers peroxisome proliferator-activated receptor gamma (PPARγ) and lipoprotein lipase (LPL). Furthermore, glucose and lactate levels in conditioned media were monitored over the period of differentiation. We found high-glucose media increasing the level of lipid accumulation and the size of single droplets whereas insulin significantly showed a dose-dependent negative effect on fat storage. However, whereas high glucose stimulated PPARγ transcription, expression levels in insulin-treated cells remained constant. Results permit assumptions that a high-glucose medium intensifies the degree of differentiation in mature adipocytes providing conditions to promote graft volume while we have identified highly concentrated insulin treatment as an inhibitor of lipid storage in the late adipogenic differentiation.
Collapse
Affiliation(s)
- Michaela Kolodziej
- Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Hannover Medical School, Hanover, Germany
| | - Sarah Strauss
- Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Hannover Medical School, Hanover, Germany
| | - Andrea Lazaridis
- Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Hannover Medical School, Hanover, Germany
| | - Vesna Bucan
- Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Hannover Medical School, Hanover, Germany
| | - Jörn W. Kuhbier
- Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Hannover Medical School, Hanover, Germany
| | - Peter M. Vogt
- Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Hannover Medical School, Hanover, Germany
| | - Sören Könneker
- Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Hannover Medical School, Hanover, Germany
| |
Collapse
|
|
19
|
Subcutaneous and Visceral Adipose-Derived Mesenchymal Stem Cells: Commonality and Diversity. Cells 2019; 8:cells8101288. [PMID: 31640218 PMCID: PMC6830091 DOI: 10.3390/cells8101288] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 10/16/2019] [Accepted: 10/17/2019] [Indexed: 12/18/2022] Open
Abstract
Adipose-derived mesenchymal stem cells (ASCs) are considered to be a useful tool for regenerative medicine, owing to their capabilities in differentiation, self-renewal, and immunomodulation. These cells have become a focus in the clinical setting due to their abundance and easy isolation. However, ASCs from different depots are not well characterized. Here, we analyzed the functional similarities and differences of subcutaneous and visceral ASCs. Subcutaneous ASCs have an extraordinarily directed mode of motility and a highly dynamic focal adhesion turnover, even though they share similar surface markers, whereas visceral ASCs move in an undirected random pattern with more stable focal adhesions. Visceral ASCs have a higher potential to differentiate into adipogenic and osteogenic cells when compared to subcutaneous ASCs. In line with these observations, visceral ASCs demonstrate a more active sonic hedgehog pathway that is linked to a high expression of cilia/differentiation related genes. Moreover, visceral ASCs secrete higher levels of inflammatory cytokines interleukin-6, interleukin-8, and tumor necrosis factor α relative to subcutaneous ASCs. These findings highlight, that both ASC subpopulations share multiple cellular features, but significantly differ in their functions. The functional diversity of ASCs depends on their origin, cellular context and surrounding microenvironment within adipose tissues. The data provide important insight into the biology of ASCs, which might be useful in choosing the adequate ASC subpopulation for regenerative therapies.
Collapse
|
|
20
|
Abstract
Adipose stem cells (ASCs) are the basis of procedures intended for tissue regeneration. These cells are heterogeneous, owing to various factors, including the donor age, sex, body mass index, and clinical condition; the isolation procedure (liposuction or fat excision); the place from where the cells were sampled (body site and depth of each adipose depot); culture surface; type of medium (whether supplemented with fetal bovine serum or xeno-free), that affect the principal phenotypic features of ASCs. The features related to ASCs heterogeneity are relevant for the success of therapeutic procedures; these features include proliferation capacity, differentiation potential, immunophenotype, and the secretome. These are important characteristics for the success of regenerative tissue engineering, not only because of their effects upon the reconstruction and healing exerted by ASCs themselves, but also because of the paracrine signaling of ASCs and its impact on recipient tissues. Knowledge of sources of heterogeneity will be helpful in the standardization of ASCs-based procedures. New avenues of research could include evaluation of the effects of the use of more homo1geneous ASCs for specific purposes, the study of ASCs-recipient interactions in heterologous cell transplantation, and the characterization of epigenetic changes in ASCs, as well as investigations of the effect of the metabolome upon ASCs behavior in culture.
Collapse
|
|
21
|
Silva KR, Baptista LS. Adipose-derived stromal/stem cells from different adipose depots in obesity development. World J Stem Cells 2019; 11:147-166. [PMID: 30949294 PMCID: PMC6441940 DOI: 10.4252/wjsc.v11.i3.147] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Revised: 01/27/2019] [Accepted: 02/28/2019] [Indexed: 02/06/2023] Open
Abstract
The increasing prevalence of obesity is alarming because it is a risk factor for cardiovascular and metabolic diseases (such as type 2 diabetes). The occurrence of these comorbidities in obese patients can arise from white adipose tissue (WAT) dysfunctions, which affect metabolism, insulin sensitivity and promote local and systemic inflammation. In mammals, WAT depots at different anatomical locations (subcutaneous, preperitoneal and visceral) are highly heterogeneous in their morpho-phenotypic profiles and contribute differently to homeostasis and obesity development, depending on their ability to trigger and modulate WAT inflammation. This heterogeneity is likely due to the differential behavior of cells from each depot. Numerous studies suggest that adipose-derived stem/stromal cells (ASC; referred to as adipose progenitor cells, in vivo) with depot-specific gene expression profiles and adipogenic and immunomodulatory potentials are keys for the establishment of the morpho-functional heterogeneity between WAT depots, as well as for the development of depot-specific responses to metabolic challenges. In this review, we discuss depot-specific ASC properties and how they can contribute to the pathophysiology of obesity and metabolic disorders, to provide guidance for researchers and clinicians in the development of ASC-based therapeutic approaches.
Collapse
Affiliation(s)
- Karina Ribeiro Silva
- Laboratory of Tissue Bioengineering, Directory of Metrology Applied to Life Sciences, National Institute of Metrology, Quality and Technology, Duque de Caxias, RJ 25250-020, Brazil
- Post-Graduation Program of Biotechnology, National Institute of Metrology, Quality and Technology, Duque de Caxias, RJ 25250-020, Brazil
| | - Leandra Santos Baptista
- Laboratory of Tissue Bioengineering, Directory of Metrology Applied to Life Sciences, National Institute of Metrology, Quality and Technology, Duque de Caxias, RJ 25250-020, Brazil
- Post-Graduation Program of Biotechnology, National Institute of Metrology, Quality and Technology, Duque de Caxias, RJ 25250-020, Brazil
- Multidisciplinary Center for Biological Research (Numpex-Bio), Federal University of Rio de Janeiro Campus Duque de Caxias, Duque de Caxias, RJ 25245-390, Brazil
| |
Collapse
|
|
22
|
He C, Li D, Gao J, Li J, Liu Z, Xu W. Inhibition of CXCR4 inhibits the proliferation and osteogenic potential of fibroblasts from ankylosing spondylitis via the Wnt/β‑catenin pathway. Mol Med Rep 2019; 19:3237-3246. [PMID: 30816502 DOI: 10.3892/mmr.2019.9980] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2018] [Accepted: 10/15/2018] [Indexed: 11/06/2022] Open
Abstract
Ankylosing spondylitis (AS) is an autoimmune condition characterized by chronic inflammation and abnormal ossification as the primary features of the disease. The aim of the present study was to investigate the role of C‑X‑C chemokine receptor type 4 (CXCR4) in ossification from patients with AS. CXCR4 expression was assessed by western blot analysis and immunohistochemistry analysis of tissues obtained from patients with AS and controls. Fibroblasts were isolated, cultured and incubated with AMD 3100 and stromal cell‑derived factor‑1 to inhibit and promote CXCR4 levels, respectively. CXCR4 was upregulated in hip synovial tissues from patients with AS compared with that observed in controls. AS fibroblasts exhibited increased proliferation and growth rates. Inhibition of CXCR4 increased the phosphorylation of β‑catenin and downregulated the expression of β‑catenin, v‑myc avian myelocytomatosis viral oncogene homolog, cyclin D1 and osteocalcin. Alizarin red staining demonstrated a decrease in biomineralization activity following the inhibition of CXCR4. These data support the hypothesis that inhibiting CXCR4 in patients with AS may suppress the ossification of fibroblasts.
Collapse
Affiliation(s)
- Chongru He
- Department of Orthopedics, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, P.R. China
| | - Dahe Li
- Department of Orthopedics, The 960th Hospital of People's Liberation Army, Tai'an, Shandong 271000, P.R. China
| | - Jinwei Gao
- Department of Orthopedics, Jiangyan Traditional Chinese Medicine Hospital, Taizhou, Jiangsu 225500, P.R. China
| | - Jia Li
- Department of Orthopedics, Jiangyan Traditional Chinese Medicine Hospital, Taizhou, Jiangsu 225500, P.R. China
| | - Zhongtang Liu
- Department of Orthopedics, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, P.R. China
| | - Weidong Xu
- Department of Orthopedics, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, P.R. China
| |
Collapse
|
|
23
|
Takahashi H, Sakata N, Yoshimatsu G, Hasegawa S, Kodama S. Regenerative and Transplantation Medicine: Cellular Therapy Using Adipose Tissue-Derived Mesenchymal Stromal Cells for Type 1 Diabetes Mellitus. J Clin Med 2019; 8:249. [PMID: 30781427 PMCID: PMC6406504 DOI: 10.3390/jcm8020249] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 02/09/2019] [Accepted: 02/13/2019] [Indexed: 02/06/2023] Open
Abstract
Type 1 diabetes mellitus (T1DM) is caused by the autoimmune targeting of pancreatic β-cells, and, in the advanced stage, severe hypoinsulinemia due to islet destruction. In patients with T1DM, continuous exogenous insulin therapy cannot be avoided. However, an insufficient dose of insulin easily induces extreme hyperglycemia or diabetic ketoacidosis, and intensive insulin therapy may cause hypoglycemic symptoms including hypoglycemic shock. While these insulin therapies are efficacious in most patients, some additional therapies are warranted to support the control of blood glucose levels and reduce the risk of hypoglycemia in patients who respond poorly despite receiving appropriate treatment. There has been a recent gain in the popularity of cellular therapies using mesenchymal stromal cells (MSCs) in various clinical fields, owing to their multipotentiality, capacity for self-renewal, and regenerative and immunomodulatory potential. In particular, adipose tissue-derived MSCs (ADMSCs) have become a focus in the clinical setting due to the abundance and easy isolation of these cells. In this review, we outline the possible therapeutic benefits of ADMSC for the treatment of T1DM.
Collapse
Affiliation(s)
- Hiroyuki Takahashi
- Department of Regenerative Medicine & Transplantation, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
- Center for Regenerative Medicine, Fukuoka University Hospital, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
- Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
| | - Naoaki Sakata
- Department of Regenerative Medicine & Transplantation, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
- Center for Regenerative Medicine, Fukuoka University Hospital, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
| | - Gumpei Yoshimatsu
- Department of Regenerative Medicine & Transplantation, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
- Center for Regenerative Medicine, Fukuoka University Hospital, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
| | - Suguru Hasegawa
- Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
| | - Shohta Kodama
- Department of Regenerative Medicine & Transplantation, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
- Center for Regenerative Medicine, Fukuoka University Hospital, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
| |
Collapse
|
|
24
|
Smith NC, Swaminathan V, Pallegar NK, Cordova C, Buchanan SC, Christian SL. CD24 is required for regulating gene expression, but not glucose uptake, during adipogenesis. Adipocyte 2018; 7:248-260. [PMID: 30231671 PMCID: PMC6768182 DOI: 10.1080/21623945.2018.1525251] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Adipose tissue dysfunction in obesity and lipodystrophy results in major health complications such as heart disease and stroke, and is associated with an increased risk of some cancers. We have previously found that the cell surface receptor CD24 regulates adipogenesis as measured by lipid accumulation and gene expression in mature adipocytes. How CD24 regulates these processes remains unknown. To begin answering this question, we first determined that CD24 does not affect glucose uptake in differentiating adipocytes in vitro. We then examined changes in global gene expression via DNA microarray in 3T3-L1 adipocytes with siRNA-mediated knock-down of CD24 expression. We found that CD24 expression is necessary for upregulation of up to 134 genes. We validated the CD24-mediated regulation of 4 of these genes during in vitro adipogenesis of 3T3-L1 and primary cells isolated from the inguinal white adipose tissue depots of CD24 knockout mice. Surprisingly, we found that only 1 of these genes was also regulated by CD24 in cells from the epididymal depot. Overall, these data suggest that CD24 is necessary for select gene expression in a depot-specific manner during adipogenesis in vitro. These findings could help elucidate the mechanisms regulating lipid accumulation in adipocytes thereby aiding in the development of novel treatment strategies for obesity and lipodystophy.
Collapse
Affiliation(s)
- Nicole C. Smith
- Department of Biochemistry, Memorial University of Newfoundland, St. John’s, Canada
- Department of Ocean Sciences, Memorial University of Newfoundland, St. John’s, Canada
| | | | - Nikitha K. Pallegar
- Department of Biochemistry, Memorial University of Newfoundland, St. John’s, Canada
| | - Christopher Cordova
- Department of Biochemistry, Memorial University of Newfoundland, St. John’s, Canada
| | - Sean C. Buchanan
- Department of Biochemistry, Memorial University of Newfoundland, St. John’s, Canada
| | - Sherri L. Christian
- Department of Biochemistry, Memorial University of Newfoundland, St. John’s, Canada
| |
Collapse
|
|
25
|
Abstract
Glucocorticoids are steroid hormones that play a key role in metabolic adaptations during stress, such as fasting and starvation, in order to maintain plasma glucose levels. Excess and chronic glucocorticoid exposure, however, causes metabolic syndrome including insulin resistance, dyslipidemia, and hyperglycemia. Studies in animal models of metabolic disorders frequently demonstrate that suppressing glucocorticoid signaling improves insulin sensitivity and metabolic profiles. Glucocorticoids convey their signals through an intracellular glucocorticoid receptor (GR), which is a transcriptional regulator. The adipocyte is one cell type that contributes to whole body metabolic homeostasis under the influence of GR. Glucocorticoids' functions on adipose tissues are complex. Depending on various physiological or pathophysiological states as well as distinct fat depots, glucocorticoids can either increase or decrease lipid storage in adipose tissues. In rodents, glucocorticoids have been shown to reduce the thermogenic activity of brown adipocytes. However, in human acute glucocorticoid exposure, glucocorticoids act to promote thermogenesis. In this article, we will review the recent studies on the mechanisms underlying the complex metabolic functions of GR in adipocytes. These include studies of the metabolic outcomes of adipocyte specific GR knockout mice and identification of novel GR primary target genes that mediate glucocorticoid action in adipocytes.
Collapse
Affiliation(s)
- Rebecca A Lee
- Endocrinology Graduate Program and Department of Nutritional Science & Toxicology, University of California Berkeley, Berkeley, CA 94720-3104, USA
| | - Charles A Harris
- Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA
| | - Jen-Chywan Wang
- Endocrinology Graduate Program and Department of Nutritional Science & Toxicology, University of California Berkeley, Berkeley, CA 94720-3104, USA
| |
Collapse
|
|
26
|
Trophic Activity and Phenotype of Adipose Tissue-Derived Mesenchymal Stem Cells as a Background of Their Regenerative Potential. Stem Cells Int 2017; 2017:1653254. [PMID: 28757877 PMCID: PMC5516761 DOI: 10.1155/2017/1653254] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 04/28/2017] [Accepted: 05/14/2017] [Indexed: 02/07/2023] Open
Abstract
There has been an increased interest in mesenchymal stem cells from adipose tissue, due to their abundance and accessibility with no ethical concerns. Their multipotent properties make them appropriate for regenerative clinical applications. It has been shown that adipose-derived stem cells (ASCs) may differ between the origin sites. Moreover, a variety of internal and external factors may affect their biological characteristics, as what we aimed to highlight in this review. It has been demonstrated that ASCs secrete multiple trophic factors that are capable of stimulating cell proliferation and differentiation and migration of various cell types. Particular attention should be given to exosomes, since it is known that they contribute to the paracrine effects of MSCs. Secretion of trophic agents by ASCs is thought to be in a greater importance for regenerative medicine applications, rather than cells engraftment to the site of injury and their differentiation ability. The surface marker profile of ASCs seems to be similar to that of the mesenchymal stem cells from bone marrow, although some molecular differences are observed. Thus, in this review, we have attempted to define trophic activity, as well as phenotypic characterization of ASCs, as crucial factors for therapeutic usage.
Collapse
|
|
27
|
Cleal L, Aldea T, Chau YY. Fifty shades of white: Understanding heterogeneity in white adipose stem cells. Adipocyte 2017; 6:205-216. [PMID: 28949833 PMCID: PMC5638386 DOI: 10.1080/21623945.2017.1372871] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 08/21/2017] [Accepted: 08/23/2017] [Indexed: 01/03/2023] Open
Abstract
The excessive expansion of white adipose tissue underlies the global obesity epidemic. However, not all fat is equal, and the impact of heterogeneity on the development and expansion of different adipose depots is becoming increasingly apparent. Two mechanisms are responsible for the growth of adipose tissue: hyperplasia (increasing adipocyte number) and hypertrophy (increasing adipocyte size). The former relies on the differentiation of adipocyte stem cells, which reside within the adipose stromal vascular fraction. Many differences in gene expression, adipogenesis, and the response to obesogenic stimuli have been described when comparing adipose stem cells from different depots. Considering that there is disparity in the pathogenicity of the depots, understanding this heterogeneity has clinically relevant implications. Here we review the current knowledge surrounding such differences, in the context of development, expansion and therapeutics. Moreover, given the importance of these differences, we suggest that careful consideration for the precise methodologies used, is essential if we are to truly understand the physiologically relevant consequences of this heterogeneity.
Collapse
Affiliation(s)
- Louise Cleal
- MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Teodora Aldea
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK
| | - You-Ying Chau
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK
| |
Collapse
|
|
28
|
Tang Y, Pan ZY, Zou Y, He Y, Yang PY, Tang QQ, Yin F. A comparative assessment of adipose-derived stem cells from subcutaneous and visceral fat as a potential cell source for knee osteoarthritis treatment. J Cell Mol Med 2017; 21:2153-2162. [PMID: 28374574 PMCID: PMC5571554 DOI: 10.1111/jcmm.13138] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Accepted: 12/30/2016] [Indexed: 02/06/2023] Open
Abstract
The intra‐articular injection of adipose‐derived stem cells (ASCs) is a novel potential therapy for patients with osteoarthritis (OA). However, the efficacy of ASCs from different regions of the body remains unknown. This study investigated whether ASCs from subcutaneous or visceral adipose tissue provide the same improvement of OA. Mouse and human subcutaneous and visceral adipose tissue were excised for ASC isolation. Morphology, proliferation, surface markers and adipocyte differentiation of subcutaneous ASCs (S‐ASCs) and visceral ASCs (V‐ASCs) were analysed. A surgically induced rat model of OA was established, and 4 weeks after the operation, S‐ASCs, V‐ASCs or phosphate‐buffered saline (PBS, control) were injected into the articular cavity. Histology, immunohistochemistry and gene expression analyses were performed 6 weeks after ASC injection. The ability of ASCs to differentiate into chondrocytes was assessed by in vitro chondrogenesis, and the immunosuppressive activity of ASCs was evaluated by co‐culturing with macrophages. The proliferation of V‐ASCs was significantly greater than that of S‐ASCs, but S‐ASCs had the greater adipogenic capacity than V‐ASCs. In addition, the infracted cartilage treated with S‐ASCs showed significantly greater improvement than cartilage treated with PBS or V‐ASCs. Moreover, S‐ASCs showed better chondrogenic potential and immunosuppression in vitro. Subcutaneous adipose tissue is an effective cell source for cell therapy of OA as it promotes stem cell differentiation into chondrocytes and inhibits immunological reactions.
Collapse
Affiliation(s)
- Yan Tang
- Institute of Stem Cell Research and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Zhang-Yi Pan
- Department of Joint Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Ying Zou
- Institute of Stem Cell Research and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Yi He
- Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University of Medicine College, Shanghai, China
| | - Peng-Yuan Yang
- Institute of Stem Cell Research and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Qi-Qun Tang
- Institute of Stem Cell Research and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Feng Yin
- Department of Joint Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.,Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, Tongji University, Shanghai, China
| |
Collapse
|