Human adipose-derived stem cells support lymphangiogenesis in vitro by secretion of lymphangiogenic factors

Ahmadzadeh, Nima; Robering, Jan W.; Kengelbach‐Weigand, Annika; Al‐Abboodi, Majida; Beier, Justus P.; Horch, Raymund E.; Boos, Anja M.

doi:10.1016/j.yexcr.2020.111816

Cited by 35 publications

(35 citation statements)

References 76 publications

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“…Growth factors secreted by ADSC transplantation (i.e., VEGF, FGF2, TGF-β, HGF, platelet-derived growth factor (PDGF), keratinocyte growth factor (KGF), fibronectin, and collagen I and increased expression of VEGFR-3) promote lymphatic regeneration [24,26,59,61]. Factors associated with lymphangiogenesis and fibrosis include: Tgfb1, suppression of which improves both fibrosis and lymphangiogenesis [18,62]; tumor necrosis factor (TNF)-α and interleukin (IL)-1 [48]; and neutrophils that increase lymphatic vessel density by increasing the number of VEGF-A/VEGFR-2 complexes and releasing VEGF-D [14].…”

Section: Discussionmentioning

confidence: 99%

Adipose-Derived Stem Cells Promote Intussusceptive Lymphangiogenesis by Restricting Dermal Fibrosis in Irradiated Tissue of Mice

Ogino

Hayashida

Yamakawa

et al. 2020

IJMS

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Currently, there is no definitive treatment for lymphatic disorders. Adipose-derived stem cells (ADSCs) have been reported to promote lymphatic regeneration in lymphedema models, but the mechanisms underlying the therapeutic effects remain unclear. Here, we tested the therapeutic effects of ADSC transplantation on lymphedema using a secondary lymphedema mouse model. The model was established in C57BL/6J mice by x-irradiation and surgical removal of the lymphatic system in situ. The number of lymphatic vessels with anti-lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunoreactivity increased significantly in mice subjected to transplantation of 7.5 × 105 ADSCs. X-irradiation suppressed lymphatic vessel dilation, which ADSC transplantation could mitigate. Proliferative cell nuclear antigen staining showed increased lymphatic endothelial cell (LEC) and extracellular matrix proliferation. Picrosirius red staining revealed normal collagen fiber orientation in the dermal tissue after ADSC transplantation. These therapeutic effects were not related to vascular endothelial growth factor (VEGF)-C expression. Scanning electron microscopy revealed structures similar to the intraluminal pillar during intussusceptive angiogenesis on the inside of dilated lymphatic vessels. We predicted that intussusceptive lymphangiogenesis occurred in lymphedema. Our findings indicate that ADSC transplantation contributes to lymphedema reduction by promoting LEC proliferation, improving fibrosis and dilation capacity of lymphatic vessels, and increasing the number of lymphatic vessels via intussusceptive lymphangiogenesis.

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Section: Discussionmentioning

confidence: 99%

Adipose-Derived Stem Cells Promote Intussusceptive Lymphangiogenesis by Restricting Dermal Fibrosis in Irradiated Tissue of Mice

Ogino

Hayashida

Yamakawa

et al. 2020

IJMS

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“…However, similar to angiogenesis, studies have found that the interaction of LECs with stem cells is crucial for expanding the lymphatic endothelial network [57,58]. Moreover, the ADSCs, despite the low production of VEGF-C, were found to enhance the growth of LECs effectively [59]. , Schwann cells exposed to CM from the coculture on SDF-1α GAS organized into significantly (p < 0.01) larger interconnected clusters than the Schwann cells exposed to CM from the coculture on gene-free scaffold.…”

Section: Discussionmentioning

confidence: 98%

SDF-1α gene-activated collagen scaffold enhances provasculogenic response in a coculture of human endothelial cells with human adipose-derived stromal cells

Laiva

O’Brien

Keogh

2021

J Mater Sci: Mater Med

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Novel biomaterials can be used to provide a better environment for cross talk between vessel forming endothelial cells and wound healing instructor stem cells for tissue regeneration. This study seeks to investigate if a collagen scaffold containing a proangiogenic gene encoding for the chemokine stromal-derived factor-1 alpha (SDF-1α GAS) could be used to enhance functional responses in a coculture of human umbilical vein endothelial cells (HUVECs) and human adipose-derived stem/stromal cells (ADSCs). Functional responses were determined by (1) monitoring the amount of junctional adhesion molecule VE-cadherin released during 14 days culture, (2) expression of provasculogenic genes on the 14th day, and (3) the bioactivity of secreted factors on neurogenic human Schwann cells. When we compared our SDF-1α GAS with a gene-free scaffold, the results showed positive proangiogenic determination characterized by a transient yet controlled release of the VE-cadherin. On the 14th day, the coculture on the SDF-1α GAS showed enhanced maturation than its gene-free equivalent through the elevation of provasculogenic genes (SDF-1α—7.4-fold, CXCR4—1.5-fold, eNOS—1.5-fold). Furthermore, we also found that the coculture on SDF-1α GAS secretes bioactive factors that significantly (p < 0.01) enhanced human Schwann cells’ clustering to develop toward Bünger band-like structures. Conclusively, this study reports that SDF-1α GAS could be used to produce a bioactive vascularized construct through the enhancement of the cooperative effects between endothelial cells and ADSCs.

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“…Transportation of injected methylene blue dye was shown across the incision site only in the treated group. 90 Similarly, ASCs have been noted to induce the formation of tubular-like structures when co-cultured with LECs in vitro, with denser lymphatic networks found with increasing concentrations of VEGF-C. 102 Ahmadzadeh et al found that ASCs stimulated lymphangiogenesis in LECs to a higher degree compared to VEGF-C. 101 To examine whether VEGF-C and ASCs exerted a synergistic effect on lymphatic regeneration in vivo, Hwang et al injected ASCs with and without the application of VEGF-C gelatin hydrogel in a mouse hind limb lymphedema model. Their results showed significantly reduced footpad thickness and higher lymphatic density at day 28 in the VEGF-C/ASC group compared to controls or either treatment group alone.…”

Section: Cell-based Therapymentioning

confidence: 99%

“…13 In general, ASCs and BMSCs act through two primary mechanisms-terminal differentiation to specialized cells such as LECs 91,92,94 or through paracrine effect on native cells, such as secretion of VEGF-C leading to mobilization of host LECs. [90][91][92]101 Conrad et al assessed the efficacy of BMSC in restoring lymphatic drainage in a mouse tail model. Using weekly subcutaneous injections of BMSC, the authors demonstrated a significant reduction in tail circumference in the stem-cell treated group.…”

Section: Cell-based Therapymentioning

confidence: 99%

Tissue Engineering Strategies for Cancer-Related Lymphedema

Asaad

Hanson

2021

Tissue Engineering Part A

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Tissue engineering has witnessed remarkable advancement in various fields of medicine and has the potential of revolutionizing the management of lymphedema. Combining approaches of biotechnology with the evolving understanding of lymphangiogenesis may offer promising treatment modalities for patients suffering from lymphedema. The strategies to lymphatic vessels tissue engineer can be grouped into four main categories: Delivery of chemokines, cytokines, and other growth factors to induce lymphangiogenesis; cell-based approach using lymphatic endothelial cells or stem-cells; scaffold-based tissue engineering; or a combination of these. This review will summarize the current approach to cancer-related lymphedema and advances in lymphatic tissue engineering strategies and the challenges facing the regeneration of lymphatic vasculature, particularly in an oncologic setting.

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Human adipose-derived stem cells support lymphangiogenesis in vitro by secretion of lymphangiogenic factors

Cited by 35 publications

References 76 publications

Adipose-Derived Stem Cells Promote Intussusceptive Lymphangiogenesis by Restricting Dermal Fibrosis in Irradiated Tissue of Mice

Adipose-Derived Stem Cells Promote Intussusceptive Lymphangiogenesis by Restricting Dermal Fibrosis in Irradiated Tissue of Mice

SDF-1α gene-activated collagen scaffold enhances provasculogenic response in a coculture of human endothelial cells with human adipose-derived stromal cells

Tissue Engineering Strategies for Cancer-Related Lymphedema

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