Differentiation of multipotent vascular stem cells contributes to vascular diseases

Tang, Zuoyin; Wang, Aijun; Yuan, F.T.; Yan, Zhiqiang; Liu, Bo; Chu, Julia; Helms, Jill A.; Li, Song

doi:10.1038/ncomms1867

Cited by 257 publications

(409 citation statements)

References 51 publications

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“…Hyperplasia of SMCs contributes to vascular disease, such as stenosis and atherosclerosis. 1,2 Although the origin of SMCs in the lesion area is controversial, [3][4][5][6] SMC migration and proliferation play a central role in disease development. Multiple cytokines or growth factors have been documented to regulate SMC migration and proliferation, 2,7,8 in which platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF)-β play important roles.…”

mentioning

confidence: 99%

XBP 1-Deficiency Abrogates Neointimal Lesion of Injured Vessels Via Cross Talk With the PDGF Signaling

Zeng

Yang

et al. 2015

ATVB

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Objective-Smooth muscle cell (SMC) migration and proliferation play an essential role in neointimal formation after vascular injury. In this study, we intended to investigate whether the X-box-binding protein 1 (XBP1) was involved in these processes. Approach and Results-In vivo studies on femoral artery injury models revealed that vascular injury triggered an immediate upregulation of XBP1 expression and splicing in vascular SMCs and that XBP1 deficiency in SMCs significantly abrogated neointimal formation in the injured vessels. In vitro studies indicated that platelet-derived growth factor-BB triggered XBP1 splicing in SMCs via the interaction between platelet-derived growth factor receptor β and the inositolrequiring enzyme 1α. The spliced XBP1 (XBP1s) increased SMC migration via PI3K/Akt activation and proliferation via downregulating calponin h1 (CNN1). XBP1s directed the transcription of mir-1274B that targeted CNN1 mRNA degradation. Proteomic analysis of culture media revealed that XBP1s decreased transforming growth factor (TGF)-β family proteins secretion via transcriptional suppression. TGF-β3 but not TGF-β1 or TGF-β2 attenuated XBP1s-induced CNN1 decrease and SMC proliferation. Conclusions-This study demonstrates for the first time that XBP1 is crucial for SMC proliferation via modulating the platelet-derived growth factor/TGF-β pathways, leading to neointimal formation. under stress conditions. [21][22][23] Under ER stress conditions, XBP1 mRNA undergoes unconventional splicing through an ER-resident kinase that possesses ribonuclease activity, the inositol-requiring enzyme 1 α (IRE1α). 24 Our recent studies and reports from other groups showed that physiological stimuli such as vascular endothelial cell growth factor could trigger XBP1 splicing in an ER stress response-independent manner. [25][26][27][28] In endothelial cells (ECs), XBP1 splicing plays diverse roles, including cell proliferation, 26 autophagy response, 29 and apoptosis. 30 In SMCs, bone morphogenetic protein-2 was reported to activate XBP1 splicing, 31 but the exact role of XBP1 in SMCs still remains unclear. In this study, we demonstrated that XBP1 splicing is crucial in PDGF-BB-induced SMC proliferation and contributes to neointima formation after vascular injury. Materials and MethodsMaterials and Methods are available in the online-only Data Supplement. Results Vascular Injury Increased XBP1 Expression and SplicingIn response to vascular injury, vascular SMCs will be activated undergoing migration, proliferation, and apoptosis. 32 To test whether XBP1 was involved in SMC activation, femoral artery injury model was introduced into the right side of C57Bl/6 mice. The injured vessels were harvested at day 1, and day 3 post surgery, whereas the left uninjured vessels were collected as control. Double immunofluorescence staining with anti-α SMC actin and antispliced XBP1 (XBP1s) or unspliced XBP1 (XBP1u) antibodies were performed on the cryo-sections. As shown in Figure 1A, low levels of XBP1s and XBP1u were detected in the uninjure...

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mentioning

confidence: 99%

XBP 1-Deficiency Abrogates Neointimal Lesion of Injured Vessels Via Cross Talk With the PDGF Signaling

Zeng

Yang

et al. 2015

ATVB

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“…To our knowledge, 8,19,39 these vascular resident stem cells can differentiate into either ECs or PCs to promote angiogenesis in vivo, but cannot acquire both kinds of cells to form capillary-like structures. Early studies demonstrated that MSCs formed capillary-like structures, composed of an endothelial tube covered by PCs.…”

Section: Mpcs Are Capillary-forming Stem Cellsmentioning

confidence: 99%

“…This transdifferentiation across germ layers has been previously demonstrated in perivascular stem/progenitor cells. 19,37,38 It is widely believed that MSCs are derived from mesoderm. Recent advances in cellular imaging and lineage tracing techniques indicated that MSCs have several different embryonic origins, such as the neural crest, in addition to mesoderm.…”

Section: Mpcs Exhibit Bipotential Pluripotencymentioning

confidence: 99%

“…[15][16][17] In a vascular remodeling setting following vascular injury, in parallel with adventitial neovascularization, adventitial progenitor cells start a process of proliferation, migration and differentiation and contribute to vascular remodeling. 18,19 Therefore, the growing vasa vasorum may serve as a vascular niche for adventitial stem cells, including mutipotent PCs, and plays an active role in vascular remodeling. 17 A transgenic mouse harboring the temperature-sensitive SV40 large T-antigen gene (tsSV40Tg mouse) expresses inactive tsSV40 in all tissues.…”

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confidence: 99%

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Immortalized multipotent pericytes derived from the vasa vasorum in the injured vasculature. A cellular tool for studies of vascular remodeling and regeneration

Kabara

Kawabe

Matsuki

et al. 2014

Laboratory Investigation

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Adventitial microvessels, vasa vasorum in the vessel walls, have an active role in the vascular remodeling, although its mechanisms are still unclear. It has been reported that microvascular pericytes (PCs) possess mesenchymal plasticity. Therefore, microvessels would serve as a systemic reservoir of stem cells and contribute to the tissues remodeling. However, most aspects of the biology of multipotent PCs (mPCs), in particular of pathological microvessels are still obscure because of the lack of appropriate methods to detect and isolate these cells. In order to examine the characteristics of mPCs, we established immortalized cells residing in adventitial capillary growing at the injured vascular walls. We recently developed in vivo angiogenesis to observe adventitial microvessels using collagen-coated tube (CCT), which also can be used as an adventitial microvessel-rich tissue. By using the CCT, CD146-or NG2-positive cells were isolated from the adventitial microvessels in the injured arteries of mice harboring a temperature-sensitive SV40 T-antigen gene. Several capillary-derived endothelial cells (cECs) and PCs (cPCs) cell lines were established. cECs and cPCs maintain a number of key endothelial and PC features. Co-incubation of cPCs with cECs formed capillary-like structure in Matrigel. Three out of six cPC lines, termed capillary mPCs demonstrated both mesenchymal stem cell-and neuronal stem cell-like phenotypes, differentiating effectively into adipocytes, osteoblasts, as well as schwann cells. mPCs differentiated to ECs and PCs, and formed capillary-like structure on their own. Transplanted DsRed-expressing mPCs were resident in the capillary and muscle fibers and promoted angiogenesis and myogenesis in damaged skeletal muscle. Adventitial mPCs possess transdifferentiation potential with unique phenotypes, including the reconstitution of capillary-like structures. Their phenotype would contribute to the pathological angiogenesis associated with vascular remodeling. These cell lines also provide a reproducible cellular tool for high-throughput studies on angiogenesis, vascular remodeling, and regeneration as well.

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“…VSCs are capable of producing neural cells, chondrocytes and mesenchymal stem cell-like cells that may subsequently differentiate into smooth muscle cells [40]. The authors of the latter study propose that the activity of VSCs may be chiefly responsible for the vascular remodelling and intimal hyperplasia typical of vascular disease, as they proliferate in response to vascular injury.…”

Section: Adult Cardiac Progenitor Cellsmentioning

confidence: 99%

We heart cultured hearts. A comparative review of methodologies for targeted differentiation and maintenance of cardiomyocytes derived from pluripotent and multipotent stem cells

Arabadjiev¹,

Petkova²,

Chakarov³

et al. 2014

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Citation: Arabadjiev A, Petkova R, Chakarov S, Pankov R, Zhelev N. We heart cultured hearts. A comparative review of methodologies for targeted differentiation and maintenance of cardiomyocytes derived from pluripotent and multipotent stem cells. AbstractHuman cell lines, including disease cell lines are often superior to routine animal models for the purposes of rapid and safe assessment of the effects of different agents that may modulate myocardial functioning under physiological and pathological conditions. There are several currently existing methodologies for derivation of cardiomyocyte-like cells by targeted differentiation from pluripotent cells and by reprogramming/ transdifferentiation from other types of cells (multipotent progenitors, somatic cells, etc). The present paper reviews the potential sources of cells capable of differentiation along the cardiomyocyte lineage; the existing methodologies for targeted differentiation, outlining the specificities of each method; and the markers for differentiation along the mesodermal and the cardiogenic lineage. The yield of robustly beating cells expressing cardio-specific proteins derived by any of the existing methods, however, still rarely exceeds 70-90 %, even with the newly developed approaches for increasing the differentiation capacity. There still is significant variance in the results obtained by different research groups and even between different experiments carried out in the same laboratory, with the same type of cells and same general type of protocol. Derivation of new lines of human pluripotent and multipotent stem cells according to standardised protocols and in completely defined; xeno-free conditions may increase the reliability and reproducibility of research and speed up the development of potential clinical applications.

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Differentiation of multipotent vascular stem cells contributes to vascular diseases

Cited by 257 publications

References 51 publications

XBP 1-Deficiency Abrogates Neointimal Lesion of Injured Vessels Via Cross Talk With the PDGF Signaling

XBP 1-Deficiency Abrogates Neointimal Lesion of Injured Vessels Via Cross Talk With the PDGF Signaling

Immortalized multipotent pericytes derived from the vasa vasorum in the injured vasculature. A cellular tool for studies of vascular remodeling and regeneration

We heart cultured hearts. A comparative review of methodologies for targeted differentiation and maintenance of cardiomyocytes derived from pluripotent and multipotent stem cells

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