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

Download Full-text

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

Download Full-text

Platelet-Rich Plasma Improves the Wound Healing Potential of Mesenchymal Stem Cells through Paracrine and Metabolism Alterations

Stem Cells International ◽

10.1155/2019/1234263 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 9

Author(s):

Barbara Hersant ◽

Mounia Sid-Ahmed ◽

Laura Braud ◽

Maud Jourdan ◽

Yasmine Baba-Amer ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Platelet Rich Plasma ◽

Public Health Problem ◽

Major Public Health Problem ◽

Dependent Manner ◽

Safe Alternative

Chronic and acute nonhealing wounds represent a major public health problem, and replacement of cutaneous lesions by the newly regenerated skin is challenging. Mesenchymal stem cells (MSC) and platelet-rich plasma (PRP) were separately tested in the attempt to regenerate the lost skin. However, these treatments often remained inefficient to achieve complete wound healing. Additional studies suggested that PRP could be used in combination with MSC to improve the cell therapy efficacy for tissue repair. However, systematic studies related to the effects of PRP on MSC properties and their ability to rebuild skin barrier are lacking. We evaluated in a mouse exhibiting 4 full-thickness wounds, the skin repair ability of a treatment combining human adipose-derived MSC and human PRP by comparison to treatment with saline solution, PRP alone, or MSC alone. Wound healing in these animals was measured at day 3, day 7, and day 10. In addition, we examined in vitro and in vivo whether PRP alters in MSC their proangiogenic properties, their survival, and their proliferation. We showed that PRP improved the efficacy of engrafted MSC to replace lost skin in mice by accelerating the wound healing processes and ameliorating the elasticity of the newly regenerated skin. In addition, we found that PRP treatment stimulated in vitro, in a dose-dependent manner, the proangiogenic potential of MSC through enhanced secretion of soluble factors like VEGF and SDF-1. Moreover, PRP treatment ameliorated the survival and activated the proliferation of in vitro cultured MSC and that these effects were accompanied by an alteration of the MSC energetic metabolism including oxygen consumption rate and mitochondrial ATP production. Similar observations were found in vivo following combined administration of PRP and MSC into mouse wounds. In conclusion, our study strengthens that the use of PRP in combination with MSC might be a safe alternative to aid wound healing.

Download Full-text

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.

Download Full-text

The Healing Effects of Conditioned Medium Derived from Mesenchymal Stem Cells on Radiation-Induced Skin Wounds in Rats

Cell Transplantation ◽

10.1177/0963689718807410 ◽

2018 ◽

Vol 28 (1) ◽

pp. 105-115 ◽

Cited By ~ 19

Author(s):

JiaYang Sun ◽

YunFeng Zhang ◽

XianJi Song ◽

Jiajing Zhu ◽

QingSan Zhu

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Conditioned Medium ◽

Radiation Dermatitis ◽

Skin Wounds ◽

Cutaneous Injury ◽

Radiation Induced

Radioactive dermatitis is caused by the exposure of skin and mucous membranes to radiation fields. The pathogenesis of radioactive dermatitis is complex and difficult to cure. Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) may serve as a promising candidate for the therapy of cutaneous wounds. The aim of this study was to investigate whether a WJ-MSC-derived conditioned medium (MSC-CM) could be used to treat radiation-induced skin wounds in rats using a radiation-induced cutaneous injury model. The present study was designed to examine MSC-CM therapy in the recovery of radiation-induced skin wounds in vitro and in vivo. Firstly, we prepared the MSC-CM and tested the effects of the MSC-CM on human umbilical vein endothelial cell proliferation in vitro. After that, we used a β-ray beam to make skin wounds in rats and tested the effects of MSC-CM on cutaneous wound healing in vivo. Our results indicated that MSC-CM secreted factors that promoted HUVEC proliferation, regeneration of sebaceous glands, and angiogenesis. Importantly, MSC-CM promoted wound healing in excess of the positive control (epidermal growth factor), with no, or smaller, scar formation. In conclusion, MSC-CM significantly accelerated wound closure and enhanced the wound healing quality. MSC-CM has a beneficial therapeutic effect on radiation-induced cutaneous injury skin in rats and in this way MSC-CM may serve as a basis of a novel cell-free therapeutic approach for radiation dermatitis.

Download Full-text

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

Download Full-text

Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Stimulated by Deferoxamine Accelerate Cutaneous Wound Healing by Promoting Angiogenesis

BioMed Research International ◽

10.1155/2019/9742765 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 11

Author(s):

Jianing Ding ◽

Xin Wang ◽

Bi Chen ◽

Jieyuan Zhang ◽

Jianguang Xu

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Wound Repair ◽

Umbilical Vein ◽

Tube Formation ◽

Diabetic Rats

The exosomes are derived from mesenchymal stem cells (MSCs) and may be potentially used as an alternative for cell therapy, for treating diabetic wounds, and aid in angiogenesis. This study, aimed to investigate whether exosomes originated from bone marrow-derived MSCs (BMSCs) preconditioned by deferoxamine (DFO-Exos) exhibited superior proangiogenic property in wound repair and to explore the underlying mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were used for assays involving cell proliferation, scratch wound healing, and tube formation. To test the effects in vivo, streptozotocin-induced diabetic rats were established. Two weeks after the procedure, histological analysis was used to measure wound-healing effects, and the neovascularization was evaluated as well. Our findings demonstrated that DFO-Exos activate the PI3K/AKT signaling pathway via miR-126 mediated PTEN downregulation to stimulate angiogenesis in vitro. This contributed to enhanced wound healing and angiogenesis in streptozotocin-induced diabetic rats in vivo. Our results suggest that, in cell-free therapies, exosomes derived from DFO preconditioned stem cells manifest increased proangiogenic ability.

Download Full-text

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.

Download Full-text

Autophagy of umbilical cord mesenchymal stem cells conduces to pro-angiogenic function of conditioned medium

10.21203/rs.3.rs-227201/v1 ◽

2021 ◽

Author(s):

Wenya Wang ◽

Xiao Li ◽

Chaochu Cui ◽

Dongling Liu ◽

Guotian Yin ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Conditioned Medium ◽

Umbilical Cord ◽

Tube Formation ◽

Dependent Manner ◽

And Control

Abstract BackgroundAngiogenesis is a key prerequisite for wound healing. The conditioned medium following culture of umbilical cord mesenchymal stem cells (UCMSCs) has a potential to promote angiogenesis, but the efficacy is very low. Autophagy is an important process in protein recycling and a contributor for cell exocrine, which maybe stimulate the release of cytokines from UCMSCs to the medium and enhance the pro-angiogenic efficacy of the conditioned medium.MethodsAutophagy in UCMSCs was induced by 100 nM, 1 µM and 10 µM rapamycin for 6-hour and then detected by LC-3 immunofluorescence staining. After induction, the cells were washed with PBS for 3 times and cultured in fresh medium without rapamycin for additional 24-hour. And then, the conditioned medium was collected for the following experiments. The angiogenic effects of different groups of conditioned medium were verified by in vitro and in vivo tube formation assays in the matrigel-coated plates and matrigel plaques injected in mouse inguinal areas. Finally, the expressions of angiogenic factors including VEGF, FGF-1, FGF-2, TGF-α, MMP-3, MMP-9, PDGF-α, PDGF-β, HIF-1α and Ang II in the autophagic and control UCMSCs were measured by q-PCR assay.ResultsRapamycin induced autophagy of UCMSCs in a dose dependent manner, but the conditioned medium in 100 nM rapamycin-induced group was with the best pro-angiogenic efficacy. Thus, this group of medium was viewed as the optimal conditioned medium. The in vivo tube formation assay showed that angiogenesis in matrigel plaques injected daily with the optimal conditioned medium was more obvious than that injected with the control conditioned medium. Further, the expressions of VEGF, FGF-2, PDGF-α, MMP-9 and HIF-1α were markedly increased in UCMSCs following treatment with 100 nM rapamycin.ConclusionAppropriate autophagy improves the pro-angiogenic efficacy of the conditioned medium, which might be utilized to optimize the applications of UCMSCs-derived conditioned medium in wound healing and tissue repair.Trial registrationNot applicable.

Download Full-text