Adipose Tissue-Derived Mesenchymal Stem Cells Facilitate Hematopoiesis in Vitro and in Vivo

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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Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo

Gut ◽

10.1136/gut.2008.154880 ◽

2008 ◽

Vol 58 (4) ◽

pp. 570-581 ◽

Cited By ~ 223

Author(s):

H Aurich ◽

M Sgodda ◽

P Kaltwasser ◽

M Vetter ◽

A Weise ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Human Adipose Tissue ◽

Hepatocyte Differentiation ◽

Adipose Tissue In Vitro

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Microvesicles enhance the mobility of human diabetic adipose tissue-derived mesenchymal stem cells in vitro and improve wound healing in vivo

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2016.04.025 ◽

2016 ◽

Vol 473 (4) ◽

pp. 1111-1118 ◽

Cited By ~ 14

Author(s):

Nhu Thuy Trinh ◽

Toshiharu Yamashita ◽

Tran Cam Tu ◽

Toshiki Kato ◽

Kinuko Ohneda ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Improve Wound Healing

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Exosomes from Gastric Cancer Suppressed Adipo-differentiation of Adipose Mesenchymal Stem Cells to Promote Cancer-associated Cachexia via miR-155/ C/EPBβ pathway

10.21203/rs.3.rs-89813/v1 ◽

2020 ◽

Author(s):

Ying Liu ◽

Dan Lin ◽

Haiyang Zhang ◽

Huiya Wang ◽

Ting Deng ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Luciferase Reporter ◽

Differentiation Capacity ◽

Healthy Donors ◽

Adipose Mesenchymal Stem Cells ◽

Polymerase Chain

Abstract BACKGROUNDCancer-associated cachexia (CAC) is defined as a multifactorial syndrome including depletion of adipose tissue and skeletal muscle. Adipose tissue wasting, as a key characteristic of CAC, occurs early and is related with poor survival. However, the influence of exosomes on adipo-differentiation in CAC remained be mysterious.METHODSOil-red staining, western blotting, and real-time polymerase chain reaction (RT-PCR) were used to investigate the adipo-differentiation capacity of A-MSCs from GC patients and healthy donors. Adipo-differentiation capacity of A-MSCs treated with exosomes from GES-1 or GC cell lines was also detected. To further explore the effects of exosomal miR-155 on adipo-differentiation in vitro, we carried out luciferase reporter assay. Finally, to evaluate the function of exosomal miR-155 in vivo, BALB/c mice were subcutaneously transplanted with SGC7901 cells transfected with lentivirus containing a miR-155 overexpressing (miR-155 OE) sequence or miR-155 shRNA (miR-155 KO) or control lentivirus(NC) to observe the change of adipo-differentiation of A-MSCs.RESULTSWe showed that miR-155 was high expressed in adipose mesenchymal stem cells (A-MSCs) isolated from GC patients, which exhibited significantly suppressed adipo-differentiation. Mechanistically, targeting C/EPBβ and suppressing C/EPBα and PPARγ by GC exosomal miR-155 was demonstrated to be involved in impairing the differentiation of A-MSCs into adipocytes. The expression of C/EPBβ C/EPBα and PPARγ were rescued through downregulating miR-155 in GC exosomes. Moreover, overexpression of miR-155 improved cancer cachexia in tumor-implanted mice, charactered by weight loss, tumor progression and low expression of C/EPBβ, C/EPBα, and PPARγ in A-MSCs as well as FABP4 in tumor-related adipose tissue. Decreasing level of miR-155 in implanted tumor blocked the anti-adipogenic effects of GC. CONCLUSIONGC exosomsal miR-155 suppressed adipo-differentiation of A-MSCs via targeting C/EPBβ of A-MSCs plays a crucial role in CAC.

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Adipose tissue-derived mesenchymal stem cells differentiated into hepatocyte-like cells in vivo and in vitro

Molecular Medicine Reports ◽

10.3892/mmr.2014.2935 ◽

2014 ◽

Vol 11 (3) ◽

pp. 1722-1732 ◽

Cited By ~ 50

Author(s):

LIBO YIN ◽

YUHUA ZHU ◽

JIANGANG YANG ◽

YIJIANG NI ◽

ZHAO ZHOU ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue

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Alterations in the Secretome of Clinically Relevant Preparations of Adipose-Derived Mesenchymal Stem Cells Cocultured with Hyaluronan

Stem Cells International ◽

10.1155/2015/421253 ◽

2015 ◽

Vol 2015 ◽

pp. 1-16 ◽

Cited By ~ 8

Author(s):

Peter Succar ◽

Edmond J. Breen ◽

Donald Kuah ◽

Benjamin R. Herbert

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Disease Progression ◽

Proinflammatory Cytokines ◽

Mechanism Of Action ◽

Stromal Vascular Fraction ◽

Slow Disease Progression

Osteoarthritis (OA) can be a debilitating degenerative disease and is the most common form of arthritic disease. There is a general consensus that current nonsurgical therapies are insufficient for younger OA sufferers who are not candidates for knee arthroplasties. Adipose-derived mesenchymal stem cells (MSCs) therapy for the treatment of OA can slow disease progression and lead to neocartilage formation. The mechanism of action is secretion driven. Current clinical preparations from adipose tissue for the treatment of OA include autologous stromal vascular fraction (SVF), SVF plus mature adipocytes, and culture-purified MSCs. Herein we have combined these human adipose-derived preparations with Hyaluronan (Hylan G-F 20: Synvisc)in vitroand measured alterations in cytokine profile. SVF plus mature adipocytes showed the greatest decreased in the proinflammatory cytokines IL-1β, IFN-γ, and VEGF. MCP-1 and MIP-1αdecreased substantially in the SVF preparations but not the purified MSCs. The purified MSC preparation was the only one to show increase in MIF. Overall the SVF plus mature adipocytes preparation may be most suited of all the preparations for combination with HA for the treatment of OA, based on the alterations of heavily implicated cytokines in OA disease progression. This will require further validation usingin vivomodels.

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Equine adipose-tissue derived mesenchymal stem cells and platelet concentrates: their association in vitro and in vivo

Veterinary Research Communications ◽

10.1007/s11259-008-9093-3 ◽

2008 ◽

Vol 32 (S1) ◽

pp. 51-55 ◽

Cited By ~ 88

Author(s):

M. Del Bue ◽

S. Riccò ◽

R. Ramoni ◽

V. Conti ◽

G. Gnudi ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Platelet Concentrates

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Hepatocyte differentiation of mesenchymal stem cells from rat peritoneal adipose tissue in vitro and in vivo

Experimental Cell Research ◽

10.1016/j.yexcr.2007.05.020 ◽

2007 ◽

Vol 313 (13) ◽

pp. 2875-2886 ◽

Cited By ~ 133

Author(s):

Malte Sgodda ◽

Hendryk Aurich ◽

Sina Kleist ◽

Ines Aurich ◽

Sarah König ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Hepatocyte Differentiation ◽

Adipose Tissue In Vitro

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Adipose Tissue-Derived Mesenchymal Stem Cells

Cells ◽

10.3390/cells10123433 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3433

Author(s):

Bruce A. Bunnell

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Immune Cell ◽

Therapeutic Potential ◽

Cell Activity ◽

Disease Status ◽

Primary Role

The long-held belief about adipose tissue was that it was relatively inert in terms of biological activity. It was believed that its primary role was energy storage; however, that was shattered with the discovery of adipokines. Scientists interested in regenerative medicine then reported that adipose tissue is rich in adult stromal/stem cells. Following these initial reports, adipose stem cells (ASCs) rapidly garnered interest for use as potential cellular therapies. The primary advantages of ASCs compared to other mesenchymal stem cells (MSCs) include the abundance of the tissue source for isolation, the ease of methodologies for tissue collection and cell isolation, and their therapeutic potential. Studies conducted both in vitro and in vivo have demonstrated that ASCs are multipotent, possessing the ability to differentiate into cells of mesodermal origins, including adipocytes, chondrocytes, osteoblast and others. Moreover, ASCs produce a broad array of cytokines, growth factors, nucleic acids (miRNAs), and other macromolecules into the surrounding milieu by secretion or in the context of microvesicles. The secretome of ASCs has been shown to alter tissue biology, stimulate tissue-resident stem cells, change immune cell activity, and mediate therapeutic outcomes. The quality of ASCs is subject to donor-to-donor variation driven by age, body mass index, disease status and possibly gender and ethnicity. This review discusses adipose stromal/stem cell action mechanisms and their potential utility as cellular therapeutics.

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Exosomes from Gastric Cancer Suppressed Adipo-differentiation of Adipose Mesenchymal Stem Cells to Promote Cancer-associated Cachexia via miR-155/ C/EPBβ pathway

10.21203/rs.3.rs-103656/v1 ◽

2020 ◽

Author(s):

Ying Liu ◽

Dan Lin ◽

Huiya Wang ◽

Haiyang Zhang ◽

Ting Deng ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Luciferase Reporter ◽

Differentiation Capacity ◽

Healthy Donors ◽

Adipose Mesenchymal Stem Cells ◽

Polymerase Chain

Abstract BACKGROUND: Cancer-associated cachexia (CAC) is defined as a multifactorial syndrome including depletion of adipose tissue and skeletal muscle. Adipose tissue wasting, as a key characteristic of CAC, occurs early and is related with poor survival. However, the influence of exosomes on adipo-differentiation in CAC remained be mysterious.METHODS: Oil-red staining, western blotting, and real-time polymerase chain reaction (RT-PCR) were used to investigate the adipo-differentiation capacity of A-MSCs from GC patients and healthy donors. Adipo-differentiation capacity of A-MSCs treated with exosomes from GES-1 or GC cell lines was also detected. To further explore the effects of exosomal miR-155 on adipo-differentiation in vitro, we carried out luciferase reporter assay. Finally, to evaluate the function of exosomal miR-155 in vivo, BALB/c mice were subcutaneously transplanted with SGC7901 cells transfected with lentivirus containing a miR-155 overexpressing (miR-155 OE) sequence or miR-155 shRNA (miR-155 KO) or control lentivirus(NC) to observe the change of adipo-differentiation of A-MSCs.RESULTS: We showed that miR-155 was high expressed in adipose mesenchymal stem cells (A-MSCs) isolated from GC patients, which exhibited significantly suppressed adipo-differentiation. Mechanistically, targeting C/EPBβ and suppressing C/EPBα and PPARγ by GC exosomal miR-155 was demonstrated to be involved in impairing the differentiation of A-MSCs into adipocytes. The expression of C/EPBβ C/EPBα and PPARγ were rescued through downregulating miR-155 in GC exosomes. Moreover, overexpression of miR-155 improved cancer cachexia in tumor-implanted mice, charactered by weight loss, tumor progression and low expression of C/EPBβ, C/EPBα, and PPARγ in A-MSCs as well as FABP4 in tumor-related adipose tissue. Decreasing level of miR-155 in implanted tumor blocked the anti-adipogenic effects of GC. CONCLUSION: GC exosomsal miR-155 suppressed adipo-differentiation of A-MSCs via targeting C/EPBβ of A-MSCs plays a crucial role in CAC.

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