Core–shell cell bodies composed of human cbMSCs and HUVECs for functional vasculogenesis

Lee, Wen-Yu; Tsai, Hung‐Wen; Chiang, Jen-Hao; Hwang, Shiaw-Min; Chen, Ding-Yuan; Hsu, Li-Wen; Hung, Yi-Wen; Chang, Yen; Sung, Hsing‐Wen

doi:10.1016/j.biomaterials.2011.07.061

Cited by 31 publications

(18 citation statements)

References 41 publications

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“…Contact coculture of ECs with MSCs can induce vascularization both in vitro and in vivo [20,[45][46][47], and thus is a promising solution to controlled vascularization enhancement in therapeutic needs. Here, we uncovered the underlying communication mechanism in MSCs-ECs coculture at molecular level by scrutinizing their transcriptional profiles separately.…”

Section: Discussionmentioning

confidence: 99%

“…Tissue engineering-based research in both two-dimensional (2D) and three-dimensional cocultures in vitro revealed that the active interaction between ECs and MSCs (or osteoprogenitor and fibroblast) induced the formation of tube-like cell aggregation structures. This result indicates that angiogenesis and prevascularization are involved in the cellcell communication and remodeling of the functional blood vessel development in vivo [5,[18][19][20][21][22][23][24][25][26]. Moreover, MSCs could repress ECs by regulating cytokine-induced leukocyte recruitment [27], while the activated ECs could regulate the MSCs-to-ECs transmigration in a leukocyte-like mechanism [28,29].…”

mentioning

confidence: 99%

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Transcriptional Profiling Reveals Crosstalk Between Mesenchymal Stem Cells and Endothelial Cells Promoting Prevascularization by Reciprocal Mechanisms

LiJunxiang

MaYing

TengRuifang

et al. 2015

Stem Cells and Development

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Mesenchymal stem cells (MSCs) show great promise in blood vessel restoration and vascularization enhancement in many therapeutic situations. Typically, the co-implantation of MSCs with vascular endothelial cells (ECs) is effective for the induction of functional vascularization in vivo, indicating its potential applications in regenerative medicine. The effects of MSCs-ECs-induced vascularization can be modeled in vitro, providing simplified models for understanding their underlying communication. In this article, a contact coculture model in vitro and an RNA-seq approach were employed to reveal the active crosstalk between MSCs and ECs within a short time period at both morphological and transcriptional levels. The RNA-seq results suggested that angiogenic genes were significantly induced upon coculture, and this prevascularization commitment might require the NF-kB signaling. NF-kB blocking and interleukin (IL) neutralization experiments demonstrated that MSCs potentially secreted IL factors including IL1b and IL6 to modulate NF-kB signaling and downstream chemokines during coculture. Conversely, RNA-seq results indicated that the MSCs were regulated by the coculture environment to a smooth muscle commitment within this short period, which largely induced myocardin, the myogenic co-transcriptional factor. These findings demonstrate the mutual molecular mechanism of MSCs-ECs-induced prevascularization commitment in a quick response.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Transcriptional Profiling Reveals Crosstalk Between Mesenchymal Stem Cells and Endothelial Cells Promoting Prevascularization by Reciprocal Mechanisms

LiJunxiang

MaYing

TengRuifang

et al. 2015

Stem Cells and Development

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“…Regulation of MSCs by endothelial cells in vasculogenesis and angiogenesis has not been delineated in detail and is an area of needed research. Lee et al described large core-shell bodies (5,000 cells per spheroid) composed of HUVECs and bone marrow MSCs, with MSCs forming the core and HUVECs forming the shell [48]. These investigators used a two-step process that took 48 hours to force a core-shell body arrangement, and the sprouting from these spheroids was seen first at day 3 after embedding in Matrigel.…”

Section: Discussionmentioning

confidence: 99%

Characterization and Angiogenic Potential of Human Neonatal and Infant Thymus Mesenchymal Stromal Cells

Wang

Mundada

Johnson

et al. 2015

Stem Cells Translational Medicine

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Mesenchymal stromal cells (MSCs) are present in large numbers in discarded neonatal and infant thymus tissue and can be isolated by an explant culture method. Explant culture‐isolated thymus MSCs demonstrate the classical characteristics of bone marrow MSCs. Thymus MSCs also possess proangiogenic qualities and deserve further consideration as a potential cell therapeutic agent to promote tissue regeneration and repair and for use in strategies to vascularize engineered tissues.

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“…Few, if any, MSC can physically incorporate into the endothelium of new blood vessels, 47,48 but play a supportive role via paracrine effects. 53,54 HIF1 is a hypoxic sensor in engineered tissue Results discussed thus far suggest that hypoxia may have an important role in vascularization of engineered tissue. Importantly, HIF1a is part of the cellular response to environmental stresses including, but not limited to, hypoxia.…”

Section: Graft-derived Vascularization May Be Governed By a Hif1-medimentioning

confidence: 98%

Tuning Graft- and Host-Derived Vascularization in Modular Tissue Constructs: A Potential Role of HIF1 Activation

Lam

Sefton²

2015

Tissue Engineering Part A

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A better understanding of the factors governing the vascularization of engineered tissues is crucial for their advancement as therapeutic platforms. Here, we studied the effect of implant volume and cell densities on the in vivo vascularization of modular engineered tissue constructs. Sub-millimeter collagen modules containing adipose-derived mesenchymal stromal cells (adMSC) and enveloped by human umbilical vein endothelial cells (HUVEC) were subcutaneously implanted in severe-combined immunodeficient mice with a beige-mutation (SCID-bg) mice. Implant volume and cell density was varied relative to a base case, defined as a 0.01 mL implant containing 1.5×10(7) adMSC/mL and 3.9×10(6) HUVEC/mL. At 7 and 14 days post-transplantation, the constructs were harvested for immunohistochemical analysis of total (CD31(+)) and graft-derived (UEA1(+)) vessel formation, hypoxia-inducible factor 1-alpha (HIF1α) expression, infiltration of host-derived leukocytes (CD45), and macrophages (F4/80). Implant volume and cell density affected the relative contributions of host- versus graft-derived vascularization, highlighting that different mechanisms underlie the two processes. Graft-derived vessel formation was most rapid and robust in implants with high HIF1α expression, namely large volume implants and implants with high adMSC and HUVEC density (p<0.01 compared to base case at day 7). Many HIF1α(+) cells were vessel-lining HUVEC, suggesting that HIF1 activation may be key to vessel assembly in the graft. Host vessel ingrowth, however, dominated the vascularization of small volume implants (of high and low adMSC density alike), which showed low HIF1α expression at day 7. Host vessels were sustained to day 14 when adMSC density alone was increased, presumably due to increased paracrine secretions. This study points to a potential role of HIF1 activation in the vascularization of tissue constructs, which may be harnessed to engineer robust vessels for therapeutic applications.

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Core–shell cell bodies composed of human cbMSCs and HUVECs for functional vasculogenesis

Cited by 31 publications

References 41 publications

Transcriptional Profiling Reveals Crosstalk Between Mesenchymal Stem Cells and Endothelial Cells Promoting Prevascularization by Reciprocal Mechanisms

Transcriptional Profiling Reveals Crosstalk Between Mesenchymal Stem Cells and Endothelial Cells Promoting Prevascularization by Reciprocal Mechanisms

Characterization and Angiogenic Potential of Human Neonatal and Infant Thymus Mesenchymal Stromal Cells

Tuning Graft- and Host-Derived Vascularization in Modular Tissue Constructs: A Potential Role of HIF1 Activation

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