Mechanical Regulation of Microvascular Angiogenesis

Ruehle, Marissa A.; Eastburn, Emily A.; LaBelle, Steven A.; Krishnan, Laxminarayanan; Weiss, Jeffrey A.; Boerckel, Joel D.; Wood, Levi B.; Guldberg, Robert E.; Willett, Nick J.

doi:10.1101/2020.01.14.906354

Cited by 13 publications

(15 citation statements)

References 62 publications

(85 reference statements)

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“…Yet how these cell behaviors are coordinated with the angiogenic genetic programs, developmental pre-patterning and mechanotransduction is far from being understood. The mechanical environment that ECs experience is also highly relevant, since it affects the way cells react to forces (Ruehle et al, 2020). In addition, the contribution of different flow-derived forces (e.g., shear stress and circumferential stretch) to specific EC behaviors involved in vascular morphogenesis still needs to be clarified.…”

Section: Resultsmentioning

confidence: 99%

Blood Flow Forces in Shaping the Vascular System: A Focus on Endothelial Cell Behavior

2020

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The endothelium is the cell monolayer that lines the interior of the blood vessels separating the vessel lumen where blood circulates, from the surrounding tissues. During embryonic development, endothelial cells (ECs) must ensure that a tight barrier function is maintained whilst dynamically adapting to the growing vascular tree that is being formed and remodeled. Blood circulation generates mechanical forces, such as shear stress and circumferential stretch that are directly acting on the endothelium. ECs actively respond to flow-derived mechanical cues by becoming polarized, migrating and changing neighbors, undergoing shape changes, proliferating or even leaving the tissue and changing identity. It is now accepted that coordinated changes at the single cell level drive fundamental processes governing vascular network morphogenesis such as angiogenic sprouting, network pruning, lumen formation, regulation of vessel caliber and stability or cell fate transitions. Here we summarize the cell biology and mechanics of ECs in response to flow-derived forces, discuss the latest advances made at the single cell level with particular emphasis on in vivo studies and highlight potential implications for vascular pathologies.

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Section: Resultsmentioning

confidence: 99%

Blood Flow Forces in Shaping the Vascular System: A Focus on Endothelial Cell Behavior

2020

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“…When engineering biomaterials to treat ischemic diseases is pivotal to promote blood reperfusion by encouraging the formation of new blood vessels. [ 29a ] As such, these biomaterials must modulate cell fate by promoting cell adhesion and migration, [ 31 ] and provide mechanical support that triggers proliferation signals via mechanotransduction. [ 32 ]…”

Section: Biomaterials Application For Cltimentioning

confidence: 99%

Therapeutic Biomaterial Approaches to Alleviate Chronic Limb Threatening Ischemia

2021

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Chronic limb threatening ischemia (CLTI) is a severe condition defined by the blockage of arteries in the lower extremities that leads to the degeneration of blood vessels and is characterized by the formation of non‐healing ulcers and necrosis. The gold standard therapies such as bypass and endovascular surgery aim at the removal of the blockage. These therapies are not suitable for the so‐called “no option patients” which present multiple artery occlusions with a likelihood of significant limb amputation. Therefore, CLTI represents a significant clinical challenge, and the efforts of developing new treatments have been focused on stimulating angiogenesis in the ischemic muscle. The delivery of pro‐angiogenic nucleic acid, protein, and stem cell‐based interventions have limited efficacy due to their short survival. Engineered biomaterials have emerged as a promising method to improve the effectiveness of these latter strategies. Several synthetic and natural biomaterials are tested in different formulations aiming to incorporate nucleic acid, proteins, stem cells, macrophages, or endothelial cells in supportive matrices. In this review, an overview of the biomaterials used alone and in combination with growth factors, nucleic acid, and cells in preclinical models is provided and their potential to induce revascularization and regeneration for CLTI applications is discussed.

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“…[1][2][3][4][5] Uterine factor for cell adhesion, growth and proliferation, and thereby have been widely used for uterus repair. [19][20][21][22][23][24][25] In the downstream application, they are usually patched onto a small defective uterus wall to achieve function regeneration. [17,[26][27][28][29] As is well known, the uterus is a hollow muscular organ, which is composed of the endometrium (inside layer), myometrium (middle layer), and the perimetrium (outside layer).…”

Section: Introductionmentioning

confidence: 99%

Reconstructable Uterus‐Derived Materials for Uterus Recovery toward Efficient Live Births

et al. 2022

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infertility caused by endometrial injuries is becoming more and more common, and ≈6% of women are suffering from uterus repair treatment. [5] Several clinical strategies, including hysteroscopic transcervical resection of adhesion, physical barriers (contraceptive device, intrauterine balloon, etc.), and hormone drugs, have been developed to repair injured uterus. [6][7][8] However, it is difficult to efficiently repair the uterus and restore fertility by these strategies, thereby leading to irreparable infertility because of intrauterine adhesion. [9][10][11] Therefore, new efficient solutions to regenerate the structure and function of the injured uterus to support live births are urgently needed.Extracellular matrix (ECM) materials derived from tissues/organs have recently received much concern in material science and regenerative medicine. [12][13][14][15][16][17][18] These ECM materials are usually fabricated by decellularization of tissues/organs, through which they well maintain the integrity of original tissues/organs. Owing to retaining physical scaffolds and biochemical signals from original tissues/organs, they have shown excellent capacities on providing favorable microenvironment Uterine factor infertility is increasingly common in modern society and has severely affected human life and health. However, the existing biomaterial scaffold-mediated systems remain limited in efficient uterus recovery, leading to low pregnancy rate and live births. Here, reconstructable uterus-derived materials (RUMs) are demonstrated by combining uterus-derived extracellular matrix and seeded chorionic villi mesenchymal stem cells for uterus recovery, achieving highly efficient live births in rats with severe uterine injury. The RUMs can be designed into different states (such as, liquid RUMs and solid RUMs) and shapes (such as, cuboid, triangular-prism, and cube) in terms of requirements. The RUMs can effectively prevent intrauterine adhesion, and promote endometrial regeneration and muscle collagen reconstruction, as well as, accelerate wound healing by constructing a physical barrier and secreting cytokines, allowing efficient uterus recovery. The injured uterus nearly achieves complete recovery after treating with the RUMs and has normal pregnancies for supporting fetal development and live births, similar to the normal rats. The study provides a regenerative medicine therapeutics for uterine factor infertility.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.202106510.

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Mechanical Regulation of Microvascular Angiogenesis

Cited by 13 publications

References 62 publications

Blood Flow Forces in Shaping the Vascular System: A Focus on Endothelial Cell Behavior

Blood Flow Forces in Shaping the Vascular System: A Focus on Endothelial Cell Behavior

Therapeutic Biomaterial Approaches to Alleviate Chronic Limb Threatening Ischemia

Reconstructable Uterus‐Derived Materials for Uterus Recovery toward Efficient Live Births

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