scholarly journals Amniotic Mesenchymal Stem Cells Can Enhance Angiogenic Capacity via MMPsIn VitroandIn Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Fei Jiang ◽  
Jie Ma ◽  
Yi Liang ◽  
Yuming Niu ◽  
Ning Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Vein ◽  
3D Culture ◽  
Positive Staining ◽  
Vascular Networks ◽  
Amniotic Mesenchymal Stem Cells ◽  
3D Culture Model

The aim of this study was to evaluate the angiogenic capacity and proteolytic mechanism of coculture using human amniotic mesenchymal stem cells (hAMSCs) with human umbilical vein endothelial cells (HUVECs)in vivoandin vitroby comparing to those of coculture using bone marrow mesenchymal stem cells with HUVEC. For thein vivoexperiment, cells (HUVEC-monoculture, HUVEC-hAMSC coculture, and HUVEC-BMMSC coculture) were seeded in fibrin gels and injected subcutaneously in nude mice. The samples were collected on days 7 and 14 and histologically analyzed by H&E and CD31 staining. CD31-positive staining percentage and vessel-like structure (VLS) density were evaluated as quantitative parameters for angiogenesis. The increases of CD31-positive staining area and VLS density in both HUVEC-hAMSC group and HUVEC-BMMSC group were found between two time points, while obvious decline of those was observed in HUVEC-only group. For thein vitroexperiment, we utilized the same 3D culture model to investigate the proteolytic mechanism related to capillary formation. Intensive vascular networks formed by HUVECs were associated with hAMSCs or BMMSCs and related to MMP2 and MMP9. In conclusion, hAMSCs shared similar capacity and proteolytic mechanism with BMMSCs on neovascularization.

scholarly journals FGF-2-Induced Human Amniotic Mesenchymal Stem Cells Seeded on a Human Acellular Amniotic Membrane Scaffold Accelerated Tendon-to-Bone Healing in a Rabbit Extra-Articular Model

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Jun Zhang ◽  
Ziming Liu ◽  
Yuwan Li ◽  
Qi You ◽  
Jibin Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Amniotic Membrane ◽  
Bone Healing ◽  
Chondrogenic Differentiation ◽  
Biomechanical Analysis ◽  
Specific Marker ◽  
Amniotic Mesenchymal Stem Cells

Background. FGF-2 (basic fibroblast growth factor) has a positive effect on the proliferation and differentiation of many kinds of MSCs. Therefore, it represents an ideal molecule to facilitate tendon-to-bone healing. Nonetheless, no studies have investigated the application of FGF-2-induced human amniotic mesenchymal stem cells (hAMSCs) to accelerate tendon-to-bone healing in vivo. Objective. The purpose of this study was to explore the effect of FGF-2 on chondrogenic differentiation of hAMSCs in vitro and the effect of FGF-2-induced hAMSCs combined with a human acellular amniotic membrane (HAAM) scaffold on tendon-to-bone healing in vivo. Methods. In vitro, hAMSCs were transfected with a lentivirus carrying the FGF-2 gene, and the potential for chondrogenic differentiation of hAMSCs induced by the FGF-2 gene was assessed using immunofluorescence and toluidine blue (TB) staining. HAAM scaffold was prepared, and hematoxylin and eosin (HE) staining and scanning electron microscopy (SEM) were used to observe the microstructure of the HAAM scaffold. hAMSCs transfected with and without FGF-2 were seeded on the HAAM scaffold at a density of 3×105 cells/well. Immunofluorescence staining of vimentin and phalloidin staining were used to confirm cell adherence and growth on the HAAM scaffold. In vivo, the rabbit extra-articular tendon-to-bone healing model was created using the right hind limb of 40 New Zealand White rabbits. Grafts mimicking tendon-to-bone interface (TBI) injury were created and subjected to treatment with the HAAM scaffold loaded with FGF-2-induced hAMSCs, HAAM scaffold loaded with hAMSCs only, HAAM scaffold, and no special treatment. Macroscopic observation, imageological analysis, histological assessment, and biomechanical analysis were conducted to evaluate tendon-to-bone healing after 3 months. Results. In vitro, cartilage-specific marker staining was positive for the FGF-2 overexpression group. The HAAM scaffold displayed a netted structure and mass extracellular matrix structure. hAMSCs or hAMSCs transfected with FGF-2 survived on the HAAM scaffold and grew well. In vivo, the group treated with HAAM scaffold loaded with FGF-2-induced hAMSCs had the narrowest bone tunnel after three months as compared with other groups. In addition, macroscopic and histological scores were higher for this group than for the other groups, along with the best mechanical strength. Conclusion. hAMSCs transfected with FGF-2 combined with the HAAM scaffold could accelerate tendon-to-bone healing in a rabbit extra-articular model.

scholarly journals IFN-γ Enhances the Efficacy of Exosomes Derived from Mesenchymal Stem Cells in Myocardial Infarction Rats via miR-21 Stimulated by STAT1

2021 ◽  
Author(s):  
Jian Zhang ◽  
Yao Lu ◽  
Yangming Mao ◽  
Yue Yu ◽  
Tianyu Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Vein ◽  
Luciferase Reporter ◽  
H9c2 Cells ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
Ifn Γ

Abstract Background: Mesenchymal stem cells (MSCs) activated with IFN-γ elicit more powerful physical effects. Exosomes (Exos) secreted from MSCs have protective against myocardial injury. The aim of this study was to investigate whether Exsos derived from IFN-γ-pretreated MSCs exhibit more potent cardioprotective function and the underlying mechanisms. Methods: Exos were isolated from MSCs (Ctrl-Exo) and IFN-γ-primed MSCs (IFN-γ-Exo) and were then delivered to H9c2 cells or human umbilical vein endothelial cells (HUVECs) in vitro under oxygen and glucose deprivation (OGD) condition or in vivo in an infarcted rat heart. RNA sequencing was to identify the different expressed functional transcription factor (TF). Quantitative reverse transcription-PCR (qPCR) was to confirm the upregulated TF and miRNA in IFN-γ-primed MSCs. Dual-luciferase reporter gene assay were to analyze the transcriptional regulation of miRNAs by STAT1. The target of miR-21-5p (miR-21) was disclosed by luciferase reporter assays and qPCR. The function of BTG2 was verified in vitro under OGD condition.Result: IFN-γ-Exo accelerated migration, tube-like structure formation, and prevented H9c2 from OGD-induced apoptosis. Similarly, IFN-γ-Exo leaded to further reduction in fibrosis size, reduced cardiomyocyte apoptosis and improved cardiac function compared to Ctrl-Exo. miR-21 was significantly upregulated in both IFN-γ-primed MSCs and IFN-γ-Exo. STAT1 transcriptionally induced miR-21 expression. Up-regulated miR-21 can inhibit the expression of BTG2. BTG2 promoted H9c2 cells apoptosis and reversed the protective effect of miR-21 under OGD environment.Conclusion: IFN-γ-Exo have enhanced therapeutic efficacy against acute MI possibly through promoting angiogenesis and anti-apoptotic effect through increasing the level of miR-21, which directly targeted on BTG2.

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

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
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.

Chondrogenic Ability of Bone Marrow Mesenchymal Stem Cells in Alginate and Collagen Sponge

2011 ◽  
Vol 474-476 ◽  
pp. 1935-1938
Author(s):  
Jiang Wu ◽  
Guang Hui Wang ◽  
Hong Zhang ◽  
Yu Ping Wu ◽  
Yang Cheng Lv ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
3D Culture ◽  
Collagen Sponge ◽  
Dimensional Structure ◽  
Cartilage Defects ◽  
Marrow Mesenchymal Stem Cells

In the present study, we have demonstrated that alginate and collagen sponge can act as scaffolds in order to support 3-dimensional structure for the differentiated bone marrow derived mesenchymal stem cells (BMSCs) during chondrogenesis in vitro and in vivo. The chondrogenic induced BMSCs were well distributed and differentiation in scaffolds system before implantation, then they produced sufficient ECM in the implants to form chondroid aggregates in vivo. In our opinion, well-differentiated BMSCs is a crucial feature of cartilage repair and only can be achieved in scaffold matrix. Furthermore, when dealing with cartilage defects, alginate seem to be superior to collagen sponge, and the combinational strategy of pre-induced BMSCs combined with alginate 3D-culture might be useful in improving conventional autologous cells transplantation or free-cells scaffolds.

scholarly journals Exosomes Secreted from Hypoxia-Preconditioned Mesenchymal Stem Cells Prevent Steroid-Induced Osteonecrosis of the Femoral Head by Promoting Angiogenesis in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Na Yuan ◽  
Zhaogang Ge ◽  
Wenchen Ji ◽  
Jia Li
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Femoral Head ◽  
Bone Loss ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Therapeutic Effects ◽  
Umbilical Vein Endothelial Cells

Recent studies have suggested that exosomes exert similar therapeutic effects to those of mesenchymal stem cells (MSCs) in regenerative medicine and MSCs-derived exosomes exhibit therapeutic effects on steroid-induced osteonecrosis of the femoral head (ONFH). Furthermore, reparative functions of exosomes from MSCs are enhanced by hypoxia treatment of the cells. However, there are no related reports about whether exosomes derived from hypoxia-preconditioned MSCs could show better therapeutic effects on steroid-induced ONFH. In vitro, we investigated the effects of hypoxia precondition on exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) from rats and the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs. In vivo, we investigated the role of exosomes from hypoxia-preconditioned BMMSCs on angiogenesis and protecting osteonecrosis in a rat ONFH model. We found that the potential of the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs was higher than exosomes derived from BMMSCs cultured under normoxia. Exosomes derived from hypoxia-preconditioned BMMSCs significantly promoted proliferation, migration, vascular endothelial growth factor (VEGF) expression, and tube formation of human umbilical vein endothelial cells (HUVECs) compared with exosomes derived from BMMSCs cultured under normoxia. Administration of exosomes derived from hypoxia-preconditioned BMMSCs significantly prevented bone loss and increased vessel volume in the femoral head compared with exosomes derived from BMMSCs cultured under normoxia. Taken together, our data suggest that exosomes derived from hypoxia-preconditioned BMMSCs exert better therapeutic effects on steroid-induced ONFH by promoting angiogenesis and preventing bone loss.

scholarly journals 3D Bone Biomimetic Scaffolds for Basic and Translational Studies with Mesenchymal Stem Cells

2018 ◽  
Vol 19 (10) ◽  
pp. 3150 ◽  
Author(s):  
Cristina Sobacchi ◽  
Marco Erreni ◽  
Dario Strina ◽  
Eleonora Palagano ◽  
Anna Villa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Repair ◽  
3D Culture ◽  
Bioactive Molecules ◽  
Specific Cell ◽  
Great Effort ◽  
Biomimetic Scaffolds

Mesenchymal stem cells (MSCs) are recognized as an attractive tool owing to their self-renewal and differentiation capacity, and their ability to secrete bioactive molecules and to regulate the behavior of neighboring cells within different tissues. Accumulating evidence demonstrates that cells prefer three-dimensional (3D) to 2D culture conditions, at least because the former are closer to their natural environment. Thus, for in vitro studies and in vivo utilization, great effort is being dedicated to the optimization of MSC 3D culture systems in view of achieving the intended performance. This implies understanding cell–biomaterial interactions and manipulating the physicochemical characteristics of biomimetic scaffolds to elicit a specific cell behavior. In the bone field, biomimetic scaffolds can be used as 3D structures, where MSCs can be seeded, expanded, and then implanted in vivo for bone repair or bioactive molecules release. Actually, the union of MSCs and biomaterial has been greatly improving the field of tissue regeneration. Here, we will provide some examples of recent advances in basic as well as translational research about MSC-seeded scaffold systems. Overall, the proliferation of tools for a range of applications witnesses a fruitful collaboration among different branches of the scientific community.

Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

2019 ◽  
Vol 98 (9) ◽  
pp. 350-355
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Portal Vein ◽  
Liver Parenchyma ◽  
Miniature Pig ◽  
Hepatic Diseases ◽  
Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

Differentiation of mesenchymal stem cells from humans and animals into insulin-producing cells: An overview in vitro induction forms

2020 ◽  
Vol 16 ◽  
Author(s):  
Bruna O. S. Câmara ◽  
Bruno M. Bertassoli ◽  
Natália M. Ocarino ◽  
Rogéria Serakides
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture Medium ◽  
Adipogenic Differentiation ◽  
Medium Composition ◽  
Cell Therapies ◽  
Insulin Producing Cells ◽  
Msc Differentiation

The use of stem cells in cell therapies has shown promising results in the treatment of several diseases, including diabetes mellitus, in both humans and animals. Mesenchymal stem cells (MSCs) can be isolated from various locations, including bone marrow, adipose tissues, synovia, muscles, dental pulp, umbilical cords, and the placenta. In vitro, by manipulating the composition of the culture medium or transfection, MSCs can differentiate into several cell lineages, including insulin-producing cells (IPCs). Unlike osteogenic, chondrogenic, and adipogenic differentiation, for which the culture medium and time are similar between studies, studies involving the induction of MSC differentiation in IPCs differ greatly. This divergence is usually evident in relation to the differentiation technique used, the composition of the culture medium, the cultivation time, which can vary from a few hours to several months, and the number of steps to complete differentiation. However, although there is no “gold standard” differentiation medium composition, most prominent studies mention the use of nicotinamide, exedin-4, ß-mercaptoethanol, fibroblast growth factor b (FGFb), and glucose in the culture medium to promote the differentiation of MSCs into IPCs. Therefore, the purpose of this review is to investigate the stages of MSC differentiation into IPCs both in vivo and in vitro, as well as address differentiation techniques and molecular actions and mechanisms by which some substances, such as nicotinamide, exedin-4, ßmercaptoethanol, FGFb, and glucose, participate in the differentiation process.

scholarly journals Lithium-Doped Biological-Derived Hydroxyapatite Coatings Sustain In Vitro Differentiation of Human Primary Mesenchymal Stem Cells to Osteoblasts

Coatings ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 781 ◽  
Author(s):  
Paula E. Florian ◽  
Liviu Duta ◽  
Valentina Grumezescu ◽  
Gianina Popescu-Pelin ◽  
Andrei C. Popescu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Doping Agent ◽  
Hydroxyapatite Coatings ◽  
3D Network ◽  
Immunofluorescence Labelling ◽  
Good Biocompatibility ◽  
Adhesion Process

This study is focused on the adhesion and differentiation of the human primary mesenchymal stem cells (hMSC) to osteoblasts lineage on biological-derived hydroxyapatite (BHA) and lithium-doped BHA (BHA:LiP) coatings synthesized by Pulsed Laser Deposition. An optimum adhesion of the cells on the surface of BHA:LiP coatings compared to control (uncoated Ti) was demonstrated using immunofluorescence labelling of actin and vinculin, two proteins involved in the initiation of the cell adhesion process. BHA:LiP coatings were also found to favor the differentiation of the hMSC towards an osteoblastic phenotype in the presence of osteoinductive medium, as revealed by the evaluation of osteoblast-specific markers, osteocalcin and alkaline phosphatase. Numerous nodules of mineralization secreted from osteoblast cells grown on the surface of BHA:LiP coatings and a 3D network-like organization of cells interconnected into the extracellular matrix were evidenced. These findings highlight the good biocompatibility of the BHA coatings and demonstrate that the use of lithium as a doping agent results in an enhanced osteointegration potential of the synthesized biomaterials, which might therefore represent viable candidates for future in vivo applications.

scholarly journals Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pegah Nammian ◽  
Seyedeh-Leili Asadi-Yousefabad ◽  
Sajad Daneshi ◽  
Mohammad Hasan Sheikhha ◽  
Seyed Mohammad Bagher Tabei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Femoral Artery ◽  
Critical Limb Ischemia ◽  
Limb Ischemia

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.

Sign in / Sign up

Export Citation Format

Share Document