Human adipose tissue-derived multipotent stem cells differentiate in vitro and in vivo into osteocyte-like cells

2007 ◽  
Vol 361 (2) ◽  
pp. 342-348 ◽  
Author(s):  
Christian Elabd ◽  
Chiara Chiellini ◽  
Ali Massoudi ◽  
Olivia Cochet ◽  
Laure-Emmanuelle Zaragosi ◽  
...  
Gut ◽  
2008 ◽  
Vol 58 (4) ◽  
pp. 570-581 ◽  
Author(s):  
H Aurich ◽  
M Sgodda ◽  
P Kaltwasser ◽  
M Vetter ◽  
A Weise ◽  
...  

2005 ◽  
Vol 332 (2) ◽  
pp. 370-379 ◽  
Author(s):  
Ying Cao ◽  
Zhao Sun ◽  
Lianming Liao ◽  
Yan Meng ◽  
Qin Han ◽  
...  

2019 ◽  
Vol 208 (3-4) ◽  
pp. 148-157
Author(s):  
Tao Luo ◽  
Xueqin Yang ◽  
Yan Sun ◽  
Xinqi Huang ◽  
Ling Zou ◽  
...  

Osteogenic differentiation of human adipose tissue-derived stem cells (hASCs) is a complex process that is regulated by multiple factors, including microRNAs (miRNAs). The miRNA miR-20a was shown to promote bone formation from bone marrow-derived mesenchymal stem cells. However, the role of miR-20a in osteogenic differentiation of hASCs remains unclear. In this study, we systematically evaluated the function of miR-20a in regulating hASC osteogenesis in vitro. hASCs were transduced with miR-20a-overexpressing and miR-20a-sponge lentiviral vectors, with green fluorescent protein (GFP) as a control. The results showed that miR-20a transcription was upregulated after hASC mineralization. Compared with the miR-20a-sponge, GFP, and hASC groups, the miR-20a-overexpressing group showed higher alkaline phosphatase (ALP) activity on days 7 and 14. Moreover, the mRNA level of ALP increased significantly in the miR-20a-overexpressing group on day 14. Furthermore, the protein of the target gene PPARγ was decreased, and the osteogenic differentiation-associated proteins ALP, osteocalcin, and RUNX2 were upregulated. hASCs anchored to HA/β-TCP revealed a healthy polygonal morphology and developed cytoplasmic extensions. miR-20a promoted osteogenic differentiation of the cell scaffold. Taken together, these data ­confirm that miRNA-20a promotes the osteogenesis of hASCs in vitro, and its essential role in vivo needs further ­investigation.


2021 ◽  
Author(s):  
Zahra Eydian ◽  
Alaleh Mohammad Ghasemi ◽  
Samira Ansari ◽  
Ali Naghi Kamali ◽  
Maryam Khosravi ◽  
...  

Abstract Background: Mesenchymal stem cells (MSCs) from human adipose tissue and bone marrow have a great potential for use in cell therapy due to their ease of isolation, expansion, and differentiation. Our intention was to isolate and promote in vitro expansion and differentiation of MSCs from human adipose and bone marrow tissue into cells with a pancreatic endocrine phenotype and to compare the potency of these cells together.Methods and Results: MSCs were pre-induced with nicotinamide, mercaptoethanol, B-27 and b-FGF in L-DMEM for 2 days and re-induced again in supplemented H-DMEM for another 3 days. Expression of five genes in differentiated beta cells was evaluated by Real-time PCR and western blotting and the potency of insulin release in response to glucose stimulation was evaluated by insulin and C-peptide ELISA kit.Quantitative RT-PCR results showed up-regulation of four genes in differentiated beta-islet cells (Insulin, Ngn-3, Pax-4 and Pdx-1) compared with the control. Western blot analysis showed that MSCs cells mainly produced proinsulin and insulin after differentiation but nestin was more expressed in pre-differentiated stem cells. Glucose and insulin secretion assay showed that insulin levels and C-peptide secretion were significantly increased in response to 10 mM glucose.Conclusions: Our study showed that both adipose and bone marrow stem cells could differentiate into functional beta-islet cells but it seems that adipose stem cells could be a better choice for treatment of diabetes mellitus according to their more safety and potency.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 495
Author(s):  
Prakash Gangadaran ◽  
Ramya Lakshmi Rajendran ◽  
Ji Min Oh ◽  
Eun Jung Oh ◽  
Chae Moon Hong ◽  
...  

Angiogenesis is defined as the generation of new blood vessels or the sprouting of endothelial cells from a pre-existing vascular network. Angiogenesis occurs during the growth and development of an organism, the response of organs or tissues to injury, and during cancer development and progression. The majority of studies on stem-cell-derived extracellular vesicles (EVs) have used cell lines, and have primarily focused on well-known solitary proteins. Here, we isolated stem cells from human adipose tissue (ADSCs), and we isolated EVs from them (ADSC-EVs). The ADSC-EVs were characterised and 20 angiogenic proteins were analysed using an angiogenic antibody array. Furthermore, we analysed the ability of ADSC-EVs to induce angiogenesis in vitro and in vivo. ADSC-EVs were positive for CD81 and negative for GM130, calnexin, and cytochrome-C. ADSC-EVs showed typical EV spherical morphology and were ~200 nm in size. ADSC-EVs were found to contain angiogenic proteins as cargo, among which interleukin 8 (IL-8) was the most abundant, followed by chemokine (C-C motif) ligand 2 (CCL2), a tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, and vascular endothelial growth factor-D (VEGF-D). ADSC-EVs treatment increased the proliferation, migration, total vessel length, total number of junctions, and junction density of endothelial cells in vitro. The results of an in vivo Matrigel plug assay revealed that ADSC-EVs induced more blood vessels in the Matrigel compared with the control. These results demonstrate that ADSC-EVs contain angiogenic proteins as cargo and promote angiogenesis in vitro and in vivo. Therefore, ADSC-EVs have potential for therapeutic use in ischaemia.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Liying Cai ◽  
Brian H Johnstone ◽  
Todd G Cook ◽  
Keith L March

Background The use of stem cells has gained much interest as a potential therapeutic approach for repair of damage caused by a variety of cardiac insults. We and others have demonstrated the ability of pluripotent adipose-derived stem cells (ASCs), to promote repair in ischemic skeletal tissues. Here we demonstrate that ASCs also stimulate a robust functional improvement following acute myocardial infarction (MI) in rats. Methods and Results ASCs were harvested from human subcutaneous adipose tissue. ASCs were characterized in vitro before in vivo testing. Growth and metabolic activity of human microvascular endothelial cells (HMVEC) cultured in growth-factor deficient minimal medium (MM) increased 1.7-fold when supplemented with a 1:1 mixture of ASC CM ( p <0.01). Sprout formation by HMVECs and migration of endothelial progenitor cell (EPC) was enhanced by 2.1 and 2.0-fold, repectively, when ASC CM was added to MM ( p <0.01). Following demonstration of potency in vitro, the ASCs were evaluated for the ability to protect and rescue ischemic myocardium in an athymic nude rat following permanent ligation of the proximal LAD region. Immediately after ligation 10 6 ASCs in 100 μl saline or carrier alone was injected into 2 sites of the peri-infarct region, then at 4 and 28 d heart function was evaluated echocardiography using a Visualsonics Vivo770. ASC-treated rats consistently exhibited better cardiac function at 1 month compared to the saline control group. LV ejection fraction of the ASC group was 56 ± 7% (mean ± SEM) vs 37 ± 3% for the control (p<0.04). Fractional shortening was 32 ± 5% (ASC) vs 19 ± 2% (p<0.04). LV volumes both at end-diastolic and end-systolic stages were lower in ASC group (311 ± 17 μl and 139 ± 21 μl, respectively) than saline group (391 ± 30 μl and 249 ± 27 μl) (p<0.03). Anterior wall thinning was attenuated in ASC group (1.6 ± .08 mm vs 1.2 ± .2, at end-diastole, p<0.03). Post-mortem histological analysis demonstrated that ASC treated hearts had lower fibrosis (26 ± 6% vs 34 ± 6%; p<0.05). Conclusion We have demonstrated that ASCs have great potential as a cell therapy to preserve heart function following ischemic insult. Given the abundant source of ASCs, therapies with these cells have a higher potential for widespread adoption compared to more rare cell types.


2021 ◽  
Vol 22 (15) ◽  
pp. 7920
Author(s):  
Myroslava Mytsyk ◽  
Giulia Cerino ◽  
Gregory Reid ◽  
Laia Gili Sole ◽  
Friedrich S. Eckstein ◽  
...  

The therapeutic potential of mesenchymal stromal/stem cells (MSC) for treating cardiac ischemia strongly depends on their paracrine-mediated effects and their engraftment capacity in a hostile environment such as the infarcted myocardium. Adipose tissue-derived stromal vascular fraction (SVF) cells are a mixed population composed mainly of MSC and vascular cells, well known for their high angiogenic potential. A previous study showed that the angiogenic potential of SVF cells was further increased following their in vitro organization in an engineered tissue (patch) after perfusion-based bioreactor culture. This study aimed to investigate the possible changes in the cellular SVF composition, in vivo angiogenic potential, as well as engraftment capability upon in vitro culture in harsh hypoxia conditions. This mimics the possible delayed vascularization of the patch upon implantation in a low perfused myocardium. To this purpose, human SVF cells were seeded on a collagen sponge, cultured for 5 days in a perfusion-based bioreactor under normoxia or hypoxia (21% and <1% of oxygen tension, respectively) and subcutaneously implanted in nude rats for 3 and 28 days. Compared to ambient condition culture, hypoxic tension did not alter the SVF composition in vitro, showing similar numbers of MSC as well as endothelial and mural cells. Nevertheless, in vitro hypoxic culture significantly increased the release of vascular endothelial growth factor (p < 0.001) and the number of proliferating cells (p < 0.00001). Moreover, compared to ambient oxygen culture, exposure to hypoxia significantly enhanced the vessel length density in the engineered tissues following 28 days of implantation. The number of human cells and human proliferating cells in hypoxia-cultured constructs was also significantly increased after 3 and 28 days in vivo, compared to normoxia. These findings show that a possible in vivo delay in oxygen supply might not impair the vascularization potential of SVF- patches, which qualifies them for evaluation in a myocardial ischemia model.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pegah Nammian ◽  
Seyedeh-Leili Asadi-Yousefabad ◽  
Sajad Daneshi ◽  
Mohammad Hasan Sheikhha ◽  
Seyed Mohammad Bagher Tabei ◽  
...  

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.


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