Defined serum‐free three‐dimensional culture of umbilical cord‐derived mesenchymal stem cells yields exosomes that promote fibroblast proliferation and migration in vitro

Umbilical cord mesenchymal stem cells (UC-MSCs) are a class of multifunctional stem cells isolated and cultured from umbilical cord. They possessed the characteristics of highly self-renewal, multi-directional differentiation potential and low immunogenicity. Its application in the field of tissue engineering and gene therapy has achieved a series of results. Recent studies have confirmed their characteristics of inhibiting tumor cell proliferation and migration to nest of cancer. The ability of UC-MSCs to support hematopoietic microenvironment and suppress immune system suggests that they can improve engraftment after hematopoietic stem cell transplantation, which shows great potential in treatment of hematologic diseases. This review will focus on the latest advances in biological characteristics and mechanism of UC-MSCs in treatment of hematological diseases.

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Umbilical cord-derived mesenchymal stem cells promote proliferation and migration in MCF-7 and MDA-MB-231 breast cancer cells through activation of the ERK pathway

Oncology Reports ◽

10.3892/or.2015.4109 ◽

2015 ◽

Vol 34 (3) ◽

pp. 1469-1477 ◽

Cited By ~ 26

Author(s):

TAO LI ◽

CHUNFU ZHANG ◽

YANLING DING ◽

WEI ZHAI ◽

KUI LIU ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cancer Cells ◽

Umbilical Cord ◽

Breast Cancer Cells ◽

Erk Pathway ◽

And Migration ◽

Mcf 7 ◽

Proliferation And Migration

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Human Glioblastoma-Derived Mesenchymal Stem Cell to Pericytes Transition and Angiogenic Capacity in Glioblastoma Microenvironment

Cellular Physiology and Biochemistry ◽

10.1159/000488429 ◽

2018 ◽

Vol 46 (1) ◽

pp. 279-290 ◽

Cited By ~ 17

Author(s):

Dongye Yi ◽

Wei Xiang ◽

Qing Zhang ◽

Yongcun Cen ◽

Qing Su ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Conditioned Medium ◽

Blue Staining ◽

Alizarin Red ◽

Differentiation Potential ◽

And Migration ◽

Proliferation And Migration ◽

Vascular Formation

Background/Aims: Tumor vascular formation and maintenance are crucial events in glioblastoma development. Mesenchymal stem cells (MSCs) have been shown to differentiate into pericytes and contribute to neovascularization in the glioma microenvironment. Moreover, glioblastoma-derived mesenchymal stem cells (gb-MSCs), which consist of CD90-MSCs and CD90+MSCs, are a subpopulation of MSCs that are more active in glioma vascularization. However, the functions of gb-MSCs and the microRNA (miRNA) modifications in the glioblastoma microenvironment have not yet been fully elucidated. Here, we focus on the pericyte differentiation potential of gb-MSCs and miRNA modifications in gb-MSCs during new vascular formation and glioblastoma growth. Methods: In vitro, surface markers of gb-MSCs were detected by flow cytometry; the differentiation potential was evaluated by Oil Red O staining, Alizarin Red staining and Alcian blue staining; the proliferation and migration of gb-MSCs in different conditioned media were analyzed by the cck8 test and wound-healing assay, respectively; gb-MSC to pericyte transition was detected by immunofluorescence staining and western blot assay; angiogenetic capacity was analyzed by tube formation assay; and levels of cytokines in different supernatant were determined by ELISA. Additionally, RNA was isolated from gb-MSCs, and miRNA modifications were analyzed using the RAffymetrix miRNA microarray Results: We showed that glioblastoma-conditioned medium increased gb-MSC proliferation and migration and was capable of inducing gb-MSC differentiation into pericytes. Glioblastoma secreted angiogenic factors and gb-MSCs incubated in malignant glioblastoma-conditioned medium formed more tube-like structures, and these cells also adhered to tube-like vessels formed by human umbilical vein endothelial cells (HUVECs) on Matrigel to maintain tumor vascular structure in vitro. miRNA expression were also modified in gb-MSCs cultured in malignant glioblastoma-conditioned medium in vitro. Conclusion: These results provide new insight into the functional effects of a subpopulation of MSCs in glioblastoma and may help in the development of novel therapies for solid tumors.

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Curcumin Supplementation Enhances Bone Marrow Mesenchymal Stem Cells to Promote the Anabolism of Articular Chondrocytes and Cartilage Repair

Cell Transplantation ◽

10.1177/0963689721993776 ◽

2021 ◽

Vol 30 ◽

pp. 096368972199377

Author(s):

Rui Zhang ◽

Qiaoxia Zhang ◽

Zhiyu Zou ◽

Zheng Li ◽

Meng Jin ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Articular Cartilage ◽

Cartilage Repair ◽

Articular Chondrocytes ◽

Immunofluorescent Staining ◽

And Migration ◽

Proliferation And Migration

Mesenchymal stem cells derived from bone marrows (BMSCs) and curcumin derived from turmeric were used for osteoarthritis (OA) treatment, respectively. We invested the effects of curcumin supplementation for BMSC therapeutic effects. In vitro, rat BMSCs were identified by dual-immunofluorescent staining of CD44 and CD90, and flow cytometry. Primary articular chondrocytes were identified by toluidine blue staining and immunofluorescent staining of Col2a1. EdU incorporation, migration assay, real-time quantitative polymerase chain reaction, and Western blot analyses were performed to evaluate the alterations of chondrocytes cocultured with BMSCs. In vivo, the rat model of OA was established by monoiodoacetic acid. After intra-articular injection of allogeneic BMSCs, articular cartilage damage and OA progression were evaluated by histological staining, and Osteoarthritis Research Society International and Mankin score evaluation. Although curcumin alone did not improve cell viability of primary articular chondrocytes, it promoted proliferation and migration of chondrocytes when cocultured with BMSCs. Meanwhile, the expression of anabolic genes in chondrocytes was remarkably increased both at mRNA and protein levels. In OA rats, curcumin and BMSCs cooperated to greatly promote articular cartilage repair and retard OA progression. Therefore, curcumin supplementation enhanced the BMSC function for the proliferation and migration of articular chondrocytes, and anabolic gene expression of extracellular matrix in articular chondrocytes in vitro, and the generation of articular cartilage in vivo. Our study shed light on the potential clinical application of curcumin cooperated with BMSCs in cartilage repair for OA treatment.

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Exosomes From Human Umbilical Cord-derived Mesenchymal Stem Cells Alleviate Osteoarthritis by Balancing the Synthesis and Degradation of Cartilage Extracellular Matrix and Regulating Macrophage Polarization

10.21203/rs.3.rs-618845/v1 ◽

2021 ◽

Author(s):

Pengdong Li ◽

Shuang Lv ◽

Wenyue Jiang ◽

Lihui Si ◽

Baojian Liao ◽

...

Keyword(s):

Stem Cells ◽

Flow Cytometry ◽

Mesenchymal Stem Cells ◽

Macrophage Polarization ◽

Inflammatory Factors ◽

Chondrocyte Apoptosis ◽

Human Umbilical Cord ◽

And Migration ◽

Proliferation And Migration

Abstract BackgroundOsteoarthritis (OA) is one of the most common joint diseases and a major public health concern. Current therapies for OA can relieve symptoms but offer no potential for cartilage regeneration. Mesenchymal stem cells (MSCs) have been widely used for the treatment of OA owing to their paracrine secretion of trophic factors, a phenomenon in which exosomes may play a major role. Here, we investigated the potential of exosomes from human umbilical cord-derived MSCs (hUC-MSCs-Exos) at alleviating OA.MethodshUC-MSCs were isolated, cultured, and identified based on the expression of MSC markers and multipotency differentiation. hUC-MSCs-Exos were harvested from hUC-MSC conditioned medium using a sequential centrifugation method. Transmission electron microscopy, dynamic light scattering, flow cytometry, and western blotting were used to identify the exosomes. The effects of hUC-MSCs-Exos on the proliferation and migration of human chondrocytes were evaluated using the cell counting kit-8, EdU-555 cell proliferation kit, and transwell assays. Annexin V-FITC/PI staining and flow cytometry were used to evaluate the effect of exosomes on chondrocyte apoptosis. An in vitro model of human articular chondrocytes treated with interleukin 1 beta (IL-1β) was used to evaluate the effects of exosomes; analyses involved using quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and western blotting. The role of exosomes in macrophage polarization was examined in the monocyte cell line, THP-1. Rats with surgically induced OA (ACLT+pMMx method) were intra-articularly injected with hUC-MSCs-Exos. The efficacy of exosome injections was assessed using hematoxylin and eosin and safranin-O and fast green staining, and immunohistochemistry.ResultsWe confirmed the superior efficacy of hUC-MSCs-Exos at promoting chondrocyte proliferation and migration and inhibiting chondrocyte apoptosis. Additionally, hUC-MSCs-Exos reversed IL-1β-induced injury in vitro. hUC-MSCs-Exos could inhibit the secretion of pro-inflammatory factors, promote the expression of anti-inflammatory factors, and regulate the polarization of macrophages. hUC-MSCs-Exos attenuated the progression of OA and prevented severe damage to the knee articular cartilage in the rat OA model. ConclusionshUC-MSCs-Exos exerted immunomodulatory and therapeutic effects in a rat model of OA. These exosomes derived from hUC-MSCs can potentially serve as treatments for OA.

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