Proangiogenic features of Wharton's jelly-derived mesenchymal stromal/stem cells and their ability to form functional vessels

Choi, Moran; Lee, Hyun-Sun; Naidansaren, Purevjargal; Kim, Hyun-Kyung; Eunju, O; Cha, Jung-Ho; Ahn, Hyunyoung; Yang, Park In; Shin, Jong-Chul; Joe, Yeonsoo

doi:10.1016/j.biocel.2012.12.001

Cited by 89 publications

(92 citation statements)

References 41 publications

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“…The lack of endothelial differentiation of WJ-MSCs was also recently reported [11]. Importantly, Choi and colleagues showed that WJ-MSCs cultured in these conditions act as a perivascular niche and stabilize blood vessels in vivo .…”

mentioning

confidence: 62%

Transition of mesenchymal stem/stromal cells to endothelial cells

Crisan

2013

Stem Cell Res Ther

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Mesenchymal stem/stromal cells (MSCs) are heterogeneous. A fraction of these cells constitute multipotent cells that can self-renew and mainly give rise to mesodermal lineage cells such as adipocytes, osteocytes and chondrocytes. The ability of MSCs to differentiate into endothelial cells remains controversial. Isolation and in vitro manipulation of MSCs before clinical application are important steps. High numbers of MSCs are needed, requiring the in vitro expansion of these clinically important cells. To this end, a well-controlled procedure for MSC isolation and maintenance in culture is necessary.

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mentioning

confidence: 62%

Transition of mesenchymal stem/stromal cells to endothelial cells

Crisan

2013

Stem Cell Res Ther

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“…Furthermore, it is also worth mentioning that not only proteins but also other molecules (such as the sugar 2′-deoxy-D-ribose) have the ability to induce EC migration [48] and that hDPSC might produce such non-protein angiogenic factors. Other MSC with chemotactic activities include Warton Jelly-derived umbilical vein MSC [49], amniotic MSC [50] and BM-MSC [45], [51], which produce high amounts of VEGF and SDF-1 [51].…”

Section: Discussionmentioning

confidence: 99%

Angiogenic Properties of Human Dental Pulp Stem Cells

et al. 2013

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Angiogenesis, the formation of capillaries from pre-existing blood vessels, is a key process in tissue engineering. If blood supply cannot be established rapidly, there is insufficient oxygen and nutrient transport and necrosis of the implanted tissue will occur. Recent studies indicate that the human dental pulp contains precursor cells, named dental pulp stem cells (hDPSC) that show self-renewal and multilineage differentiation capacity. Since these cells can be easily isolated, cultured and cryopreserved, they represent an attractive stem cell source for tissue engineering. Until now, only little is known about the angiogenic abilities and mechanisms of the hDPSC. In this study, the angiogenic profile of both cell lysates and conditioned medium of hDPSC was determined by means of an antibody array. Numerous pro-and anti-angiogenic factors such as vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1) and endostatin were found both at the mRNA and protein level. hDPSC had no influence on the proliferation of the human microvascular endothelial cells (HMEC-1), but were able to significantly induce HMEC-1 migration in vitro. Addition of the PI3K-inhibitor LY294002 and the MEK-inhibitor U0126 to the HMEC-1 inhibited this effect, suggesting that both Akt and ERK pathways are involved in hDPSC-mediated HMEC-1 migration. Antibodies against VEGF also abolished the chemotactic actions of hDPSC. Furthermore, in the chicken chorioallantoic membrane (CAM) assay, hDPSC were able to significantly induce blood vessel formation. In conclusion, hDPSC have the ability to induce angiogenesis, meaning that this stem cell population has a great clinical potential, not only for tissue engineering but also for the treatment of chronic wounds, stroke and myocardial infarctions.

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“…α-SMA, the specific marker of smooth muscle cells and EndoMT [22], [23], showed a very low level of expression in untreated cells. In contrast, low concentrations of SFO (10–30 µg/ml) treatment significantly increased α-SMA expression at 6 and 12 h ( Fig.…”

Section: Resultsmentioning

confidence: 90%

Finding ATF4/p75NTR/IL-8 Signal Pathway in Endothelial–Mesenchymal Transition by Safrole Oxide

et al. 2014

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Targeting the endothelial-to-mesenchymal transition (EndoMT) may be a novel therapeutic strategy for cancer and various diseases induced by fibrosis. We aimed to identify a small chemical molecule as an inducer of EndoMT and find a new signal pathway by using the inducer. Safrole oxide (SFO), 50 µg/ml, could most effectively induce EndoMT within 12 h. To understand the underlying molecular mechanism, we performed microarray, quantitative real-time PCR and western blot analysis to find key factors involved in SFO-induced EndoMT and demonstrated the involvement of the factors by RNAi. The expression of activating transcription factor 4 (ATF4), p75 neurotrophin receptor (p75NTR), and interleukin 8 (IL-8) was greatly increased in SFO-induced EndoMT. Knockdown of ATF4 inhibited the SFO-induced EndoMT completely, and knockdown of p75NTR or IL-8 partially inhibited the EndoMT, which suggests that all three factors were involved in the process. Furthermore, knockdown of p75NTR inhibited the SFO-increased IL-8 expression and secretion, and knockdown of ATF4 inhibited SFO-increased p75NTR level significantly. The ATF4/p75NTR/IL-8 signal pathway may have an important role in EndoMT induced by SFO. Our findings support potential novel targets for the therapeutics of cancer and fibrosis disease.

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Proangiogenic features of Wharton's jelly-derived mesenchymal stromal/stem cells and their ability to form functional vessels

Cited by 89 publications

References 41 publications

Transition of mesenchymal stem/stromal cells to endothelial cells

Transition of mesenchymal stem/stromal cells to endothelial cells

Angiogenic Properties of Human Dental Pulp Stem Cells

Finding ATF4/p75NTR/IL-8 Signal Pathway in Endothelial–Mesenchymal Transition by Safrole Oxide

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