Multiple paracrine factors secreted by mesenchymal stem cells contribute to angiogenesis

Kwon, Hyuk Min; Hur, Sung Mo; Park, Keon Young; Kim, Chun Ki; Kim, Yong Man; Kim, Hyun Soo; Shin, Ha Cheol; Won, Moo Ho; Ha, Kwon Soo; Kwon, Young Guen; Lee, Dong Heon; Kim, Young Myeong

doi:10.1016/j.vph.2014.06.004

Cited by 164 publications

(147 citation statements)

References 48 publications

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“…Paracrine actions have been considered as the predominant mechanism for the role of mesenchymal stem cells (MSCs) in tissue repair (Kinnaird et al 2004b, Togel et al 2007, Camussi et al 2010. It has been proposed that condition medium from MSCs was effective for reducing myocardial ischemia (Jiang et al 2013), improving limb reperfusion (Kinnaird et al 2004b, Kwon et al 2014 and protecting against acute kidney injury (Togel et al 2007, Camussi et al 2010. Recently, several studies have reported that bone marrow stem cells (BMSCs) could induce the regeneration of thin endometrium and injured endometrium in animal experiments (Alawadhi et al 2014, Jing et al 2014, Kilic et al 2014.…”

Section: Introductionmentioning

confidence: 99%

“…Therapeutic angiogenesis by stem cell-based approaches has received increasing attention because stem cells could secrete many angiogenesisenhancing cytokines and growth factors (Boomsma & Geenen 2012, Rahbarghazi et al 2013, Kwon et al 2014. Human endometrial mesenchymal stem cells derived from menstrual blood (MenSCs) have emerged as attractive, novel adult stem cells that are easily obtained and have demonstrated a potential capacity for clinical therapy.…”

Section: Introductionmentioning

confidence: 99%

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Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways

et al. 2016

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Intrauterine adhesions are common acquired endometrial syndromes secondary to endometrial injury, with limited effective therapies. Recently, several studies have reported that bone marrow stem cells (BMSCs) could repair injured endometrium in animal experiments. However, the role of stem cells in endometrial injury repair and its therapeutic mechanisms remain unclear. Here, we established mouse endometrial injury model and examined the benefit of human endometrial mesenchymal stem cells derived from menstrual blood (MenSCs) in restoration of injured endometrium. Injured endometrium exhibited significantly accelerated restoration at Day 7 after MenSCs transplantation, with increased endometrial thickness and microvessel density. Moreover, the fertility of mice with injured endometrium was improved, with higher conception rate (53.57% vs 14.29%, P = 0.014) and larger embryo number (3.1 ± 0.6 vs 0.9 ± 0.7, P = 0.030) in MenSCs group than control group, while no difference was found in undamaged horns between two groups. Conditioned medium from MenSCs (MenSCs-CM) could decrease H 2 O 2 -induced apoptosis of human umbilical vein endothelial cells (HUVECs) and promote proliferation, migration and angiogenesis. Angiogenesis effect of MenSCs-CM was also confirmed in Matrigel plug assay in mice. Furthermore, we discovered that MenSCs-CM could activate AKT and ERK pathways and induce the overexpression of eNOS, VEGFA, VEGFR1, VEGFR2 and TIE2 in HUVECs, which are critical in MenSCs-CM-induced angiogenesis. Angiogenesis induced by MenSCs-CM could be reversed by inhibitors of AKT and/or ERK. Taken together, we concluded that MenSCs could restore injured endometrium and improve the fertility of the endometrial injury mice, which was partially attributed to angiogenesis induced by MenSCs.Reproduction (2016) 152 389-402

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways

et al. 2016

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“…Previous studies have reported many growth factors and cytokines derived from the CM of various stem cells [19][20][21][85][86][87][88][89], which could be responsible for the paracrine protective effects of stem cells against several diseases. Consequently, the use of stem cells CM instead of direct implantation of stem cells may be a feasible approach to overcome the limitations of current cell-based therapy.…”

Section: Secretome As a Therapeutic Strategy: Conditioned Mediamentioning

confidence: 99%

Regenerative Medicine: A New Paradigm in Bone Regeneration

Chaparro¹,

Linero²

2016

Advanced Techniques in Bone Regeneration

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Bone defects are the cause of functional disability and the restoration of skeletal function remains an important challenge on orthopedics, neurosurgery and oral and maxillofacial surgery. Because of the limitations of the currently used techniques for the reconstruction of bone defects and the difficulties for the implementation of new therapeutic strategies, a new paradigm in the field of reconstructive surgery has arisen, leading to tissue engineering and regenerative medicine. Mesenchymal stem cells (MSC) have emerged as a promising alternative for the treatment of bone lesions. It was postulated that the therapeutic action was the result of proliferation and differentiation of MSCs, replacing injured tissue. However, recent studies have shown that MSCs secrete a number of trophic factors that have a strong effect during repair and tissue regeneration. This represents a shift from a paradigm centered on MSC proliferation and differentiation to a new paradigm in which the MSCs exert their beneficial effect by the secretion of paracrine factors that induce endogenous repair mechanisms. This chapter will bring together basic and clinical aspects, focused on novel findings on MSC paracrine effect and the development of new therapeutic strategies based on growth factors, cytokines and signaling molecules involved in bone regeneration.

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“…MSC activate endogenous cellular repair programs by releasing various secretory proteins such as fibroblast growth factor, epidermal growth factor, insulin-like growth factor and monocyte chemoattractant protein-1 [12]. MSCs have also been shown to induce angiogenesis and vascular remodeling via factors such as vascular endothelial growth factor, angiopoietins and hepatocyte growth factor [13]. Additionally, MSCs secrete IL-10, IL-6 and nitric oxide which induce a localized anti-inflammatory state, thereby facilitating the healing of damaged tissue [14].…”

Section: Phenotype Of Mscsmentioning

confidence: 99%

Mesenchymal stem cell-based therapy for ischemic stroke

et al. 2016

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Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field.

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Multiple paracrine factors secreted by mesenchymal stem cells contribute to angiogenesis

Cited by 164 publications

References 48 publications

Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways

Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways

Regenerative Medicine: A New Paradigm in Bone Regeneration

Mesenchymal stem cell-based therapy for ischemic stroke

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