Mesenchymal Stem/Stromal Cells from the Placentae of Growth Restricted Pregnancies Are Poor Stimulators of Angiogenesis

Umapathy, Anandita; McCall, Alexandra; Sun, Cherry; Boss, Anna; Gamage, Teena; Brooks, Anna; Chamley, Lawrence; James, Joanna L.

doi:10.1007/s12015-020-09959-8

Cited by 11 publications

(10 citation statements)

References 37 publications

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“…43 ous research studies have demonstrated that the paracrine secretion of proangiogenic factors from MSCs is inadequate, and thus additional proangiogenic factors are needed to ensure their therapeutic efficacy. 44,45 Our previous study proved that the proangiogenic effects of ISL1-MSCs were much stronger than those of control MSCs and also showed that ISL1-MSCs could promote cell survival in the MI model and enhance its paracrine function to protect myocardial cells. 9 In this study, we further isolated exosomes from ISL1-MSCs and found that ISL1-MSCs-Exo also showed enhanced proangiogenic effects compared to exosomes isolated from MSCs-Exo in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 97%

“…Therapies based on MSC-derived exosomes have been demonstrated to decrease myocardial ischemia and reperfusion injury after MI and promote ischemic hindlimb recovery . However, numerous research studies have demonstrated that the paracrine secretion of proangiogenic factors from MSCs is inadequate, and thus additional proangiogenic factors are needed to ensure their therapeutic efficacy. , …”

Section: Discussionmentioning

confidence: 99%

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Islet-1 Mesenchymal Stem Cells-Derived Exosome-Incorporated Angiogenin-1 Hydrogel for Enhanced Acute Myocardial Infarction Therapy

Ning

Zhao

et al. 2022

ACS Appl. Mater. Interfaces

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Although stem cell-derived exosomes have been recognized as new candidates for cell-free treatment in myocardial infarction (MI), the challenge to improve the exosome retention in ischemic tissue remains. Our previous research indicated that islet-1(ISL1) overexpression enhances the paracrine function of mesenchymal stem cells (MSCs) and promotes angiogenesis in a model of MI. In this study, genetically engineered ISL1-MSC-derived exosomes (ISL1-MSCs-Exo) were collected, and the contents were analyzed by exosomal RNA sequencing. Next, we investigated if ISL1-MSCs-Exo could exert therapeutic effects and their incorporation into a new angiogenin-1 hydrogel (Ang-1 gel) could boost the retention of exosomes and further enhance their protective effects. Our results demonstrated that ISL1-MSCs-Exo could play a therapeutic role in vitro and in vivo, which might be due to changed exosomal contents. Ang-1 gel increased the retention and enhanced the anti-apoptosis, proliferation, and angiogenic capacity of ISL1-MSCs-Exo in endothelial cells. Echocardiography revealed that Ang-1 gel significantly augment the therapeutic effects of ISL1-MSCs-Exo for MI. The main mechanism might result from increased retention of ISL1-MSCs-Exo, herein enhanced pro-angiogenetic effects in an ischemic heart. Taken together, our findings indicated that ISL1-MSCs-Exo had endothelium-protective and pro-angiogenic abilities alone and Ang-1 gel could notably retain ISL1-MSCs-Exo at ischemic sites, which improved the survival and angiogenesis of endothelial cells and accelerated the recovery of MI. These results not only shed light on the therapeutic mechanism of ISL1-MSCs-Exo incorporated with Ang-1 gel but also offer a promising therapeutic option for ischemic disease.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Islet-1 Mesenchymal Stem Cells-Derived Exosome-Incorporated Angiogenin-1 Hydrogel for Enhanced Acute Myocardial Infarction Therapy

Ning

Zhao

et al. 2022

ACS Appl. Mater. Interfaces

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“…Imaging of fluorescent intensity demonstrated a significant reduction of both collagen I and fibronectin in FGRadv CDM, with striking differences in structural organization (Figure 7). To determine whether matrix was uniformly deposited by both control and FGRadv FBs, however, we stained both control and FGRadv CDM with thrombospondin I, a matrix protein that has been shown to be expressed in similar levels within placental stromal cells of normal and growth-restricted pregnancies (38). Both immunofluorescence and gray-scale imaging of thrombospondin demonstrate a similar appearance of the matrix and confirm that the differences seen in collagen I and fibronectin are not the result of a scant matrix in FGRadv CDM (Figure 7).…”

Section: Fgradv Cdm Exhibit Differential Expression Of Key Extracellular Matrix Proteinsmentioning

confidence: 99%

“…To test this, we chose to query thrombospondin-1. While thrombospondin-1 has been shown to be expressed at similar levels within placental stromal cells of both normal and growth-restricted pregnancies (38), it has also been shown to carry significant anti-angiogenic properties in non-placental tissue (51)(52)(53). Thus, we chose this particular matrix protein, hypothesizing that this ECM protein would be seen in either similar or even greater amounts in FGRadv CDM.…”

Section: Fgradv Cdm Exhibit Differential Expression Of Key Extracellular Matrix Proteinsmentioning

confidence: 99%

Human placental villous stromal extracellular matrix regulates fetoplacental angiogenesis in severe fetal growth restriction

Gumina

McPeak

et al. 2021

Clinical Science

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Pregnancies complicated by severe, early-onset fetal growth restriction with abnormal Doppler velocimetry (FGRadv) have a sparse villous vascular tree secondary to impaired angiogenesis. As endothelial cell (EC) and stromal matrix interactions are key regulators of angiogenesis, we investigated the role of placental stromal villous matrix on fetoplacental EC angiogenesis. We have developed a novel model of generating placental fibroblast (FB) cell-derived matrices (CDMs), allowing us to interrogate placenta-specific human EC and stromal matrix interactions and their effects on fetoplacental angiogenesis. We found that as compared with control ECs plated on control matrix, FGRadv ECs plated on FGRadv matrix exhibited severe migrational defects, as measured by velocity, directionality, accumulated distance, and Euclidean distance in conjunction with less proliferation. However, control ECs, when interacting with FGRadv CDM, also demonstrated significant impairment in proliferation and migratory properties. Conversely several angiogenic attributes were rescued in FGRadv ECs subjected to control matrix, demonstrating the importance of placental villous stromal matrix and EC-stromal matrix interactions in regulation of fetoplacental angiogenesis.

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“…A clear example of this is seen in trisomy 21 placentae that feature impaired syncytiotrophoblast fusion and function, where co-culture of trisomy 21 cytotrophoblasts with mesenchymal cells from normal placentae increases cytotrophoblast fusion, an effect partly attributed to the higher Activin-A secretion by the normal mesenchymal cells [ 170 ]. Indeed, the paracrine effects of mesenchymal stromal cells (MSCs) on blood vessel growth and function in a range of tissues, including the placenta, are well described, with alterations observed in pregnancy pathologies [ 171 ]. However, paracrine implications of other mesenchymal components of the villus core have not been well studied, and this is an important area for future work.…”

Section: Introductionmentioning

confidence: 99%

Modelling human placental villous development: designing cultures that reflect anatomy

James

Lissaman

Nursalim

et al. 2022

Cell. Mol. Life Sci.

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The use of in vitro tools to study trophoblast differentiation and function is essential to improve understanding of normal and abnormal placental development. The relative accessibility of human placentae enables the use of primary trophoblasts and placental explants in a range of in vitro systems. Recent advances in stem cell models, three-dimensional organoid cultures, and organ-on-a-chip systems have further shed light on the complex microenvironment and cell–cell crosstalk involved in placental development. However, understanding each model’s strengths and limitations, and which in vivo aspects of human placentation in vitro data acquired does, or does not, accurately reflect, is key to interpret findings appropriately. To help researchers use and design anatomically accurate culture models, this review both outlines our current understanding of placental development, and critically considers the range of established and emerging culture models used to study this, with a focus on those derived from primary tissue.

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Mesenchymal Stem/Stromal Cells from the Placentae of Growth Restricted Pregnancies Are Poor Stimulators of Angiogenesis

Cited by 11 publications

References 37 publications

Islet-1 Mesenchymal Stem Cells-Derived Exosome-Incorporated Angiogenin-1 Hydrogel for Enhanced Acute Myocardial Infarction Therapy

Islet-1 Mesenchymal Stem Cells-Derived Exosome-Incorporated Angiogenin-1 Hydrogel for Enhanced Acute Myocardial Infarction Therapy

Human placental villous stromal extracellular matrix regulates fetoplacental angiogenesis in severe fetal growth restriction

Modelling human placental villous development: designing cultures that reflect anatomy

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