Translational models of tumor angiogenesis: A nexus of in silico and in vitro models

Soleimani, Shirin; Shamsi, Milad; Ghazani, Mehran Akbarpour; Modarres, Hassan Pezeshgi; Valente, Karolina Papera; Saghafian, Mohsen; Mohammadi, Mehdi; Akbari, Mohsen; Sanati‐Nezhad, Amir

doi:10.1016/j.biotechadv.2018.01.013

Cited by 43 publications

(30 citation statements)

References 147 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sung et al, ; K.E. Sung & Beebe, ; Ma, Middleton, You, & Sun, ; Mi et al, ; Soleimani et al, ; Staton et al, ; Yamada & Cukierman, ; Zhang & Radisic, ; Zheng et al, ). Some of the features not simulated in 2D culture include but are not limited to cell‐cell and cell‐matrix signaling, transport studies, and impact of mechanical and chemical gradients on cellular response.…”

Section: Introductionmentioning

confidence: 99%

“…Groups have utilized subtractive and additive tissue engineering processes to form microfluidic collagen scaffolds (Bettinger, Borenstein, & Tao, ; Bhatia & Ingber, ; Peela et al, ; Tien, ). Scaffolds with complex microfluidic networks have also been formed using additive methods of combining layers of natural materials formed with lithographic techniques and have been used to investigate various behaviors such as cell‐cell interactions during angiogenesis or metastasis, extravasation of breast cancer cells and interactions with the endothelium (Bhatia & Ingber, ; Bischel, Young, Mader, & Beebe, ; Farahat et al, ; Ghousifam et al, ; Jeon et al, ; Lee et al, ; Mi et al, ; Nagaraju et al, ; Peela et al, ; Price et al, ; Soleimani et al, ; Song et al, ; Y. Ma et al, ; Zheng et al, ). While these microfluidic devices have provided insight into tumor behavior, the in vitro platforms consist of small number of cells limiting the use of biological assays such as polymerase chain reaction or enzyme‐linked immunosorbent assay, or they lack a continuous endothelium failing to recapitulate the in vivo tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

“…Groups have utilized subtractive and additive tissue engineering processes to form microfluidic collagen scaffolds (Bettinger, Borenstein, & Tao, 2012;Bhatia & Ingber, 2014;Peela et al, 2017;Tien, 2014). Scaffolds with complex microfluidic networks have also been formed using additive methods of combining layers of natural materials formed with lithographic techniques and have been used to investigate various behaviors such as cell-cell interactions during angiogenesis or metastasis, extravasation of breast cancer cells and interactions with the endothelium (Bhatia & Ingber, 2014;Bischel, Young, Mader, & Beebe, 2013;Farahat et al, 2012;Ghousifam et al, 2017;Jeon et al, 2015;Lee et al, 2014;Mi et al, 2016;Nagaraju et al, 2018;Peela et al, 2017;Price et al, 2008;Soleimani et al, 2018;Song et al, 2009;Y. Ma et al, 2018;Zheng et al, 2012).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Vascularized microfluidic platforms to mimic the tumor microenvironment

Michna

Gadde

Özkan

et al. 2018

Biotech & Bioengineering

View full text Add to dashboard Cite

Microfluidic technology has led to the development of advanced in vitro tumor platforms that overcome the challenges of in vivo animal and in vitro two dimensional models. This paper presents platform designs and methods used to develop complex vascularized in vitro models to mimic the tumor microenvironment. Features of these platforms include a continuous, aligned endothelium that allows for cell-cell interactions between vasculature and tumor cells. A novel platform for fabrication of a single endothelialized microchannel encased within a collagen platform hosting breast cancer cells was developed and utilized to study the influence of cellular interaction on transport phenomenon through vasculature in a hyperpermeable tumor microenvironment. This platform relies on subtractive tissue engineering fabrication techniques. Through confocal imaging we have demonstrated that the platform produces enhanced vessel leakiness recapitulating physiological features of the tumor microenvironment. The influence of tumor endothelial interactions on transport of particles was also demonstrated. Additionally, we designed two more complex and intricate endothelialized microfluidic networks by combining lithographic techniques with additive tissue engineering methods. We created a network platform consisting of interconnected microchannels to model a highly vascularized system and successfully perfused the system with fluorescent particles. Finally, we developed a physiologically representative in vitro microfluidic platform with vasculature patterned from in vivo data showing the versatility of these systems to replicate the complex geometries of tumor microvasculature and dynamically measured particle transport. Overall, we have shown the ability to develop functional microfluidic vascular tumor platforms of varying complexities and demonstrated their utility for studying spatial particle transport within these systems.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Vascularized microfluidic platforms to mimic the tumor microenvironment

Michna

Gadde

Özkan

et al. 2018

Biotech & Bioengineering

View full text Add to dashboard Cite

show abstract

“…The stress generated as a result of tumor growth compresses lymphatic vessels at the center zone of the tumor rendering them nonfunctional (Padera et al, 2004;Jain et al, 2014). Also tumor vessels are notoriously leaky and discharge inordinately high values of transcapillary fluid into the interstitium (Heldin et al, 2004;Dewhirst & Secomb, 2017;Soleimani et al, 2018). Taken together, vessel leakiness and lack of functional lymphatics give rise to an interstitial fluid pressure (IFP) that uniformly increases throughout central regions of the tumor while it steeply declines at the tumor periphery (Heldin et al, 2004;Chauhan et al, 2011;Liu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Magnetically assisted intraperitoneal drug delivery for cancer chemotherapy

et al. 2018

Self Cite

View full text Add to dashboard Cite

Intraperitoneal (IP) chemotherapy has revived hopes during the past few years for the management of peritoneal disseminations of digestive and gynecological cancers. Nevertheless, a poor drug penetration is one key drawback of IP chemotherapy since peritoneal neoplasms are notoriously resistant to drug penetration. Recent preclinical studies have focused on targeting the aberrant tumor microenvironment to improve intratumoral drug transport. However, tumor stroma targeting therapies have limited therapeutic windows and show variable outcomes across different cohort of patients. Therefore, the development of new strategies for improving the efficacy of IP chemotherapy is a certain need. In this work, we propose a new magnetically assisted strategy to elevate drug penetration into peritoneal tumor nodules and improve IP chemotherapy. A computational model was developed to assess the feasibility and predictability of the proposed active drug delivery method. The key tumor pathophysiology, including a spatially heterogeneous construct of leaky vasculature, nonfunctional lymphatics, and dense extracellular matrix (ECM), was reconstructed in silico. The transport of intraperitoneally injected magnetic nanoparticles (MNPs) inside tumors was simulated and compared with the transport of free cytotoxic agents. Our results on magnetically assisted delivery showed an order of magnitude increase in the final intratumoral concentration of drug-coated MNPs with respect to free cytotoxic agents. The intermediate MNPs with the radius range of 200-300 nm yield optimal magnetic drug targeting (MDT) performance in 5-10 mm tumors while the MDT performance remains essentially the same over a large particle radius range of 100-500 nm for a 1 mm radius small tumor. The success of MDT in larger tumors (5-10 mm in radius) was found to be markedly dependent on the choice of magnet strength and tumor-magnet distance while these two parameters were less of a concern in small tumors. We also validated in silico results against experimental results related to tumor interstitial hypertension, conventional IP chemoperfusion, and magnetically actuated movement of MNPs in excised tissue.

show abstract

“…Another interesting avenue is the development of in silico models capable of exploiting patient-specific data to build personalized medical treatments, such as three-dimensional mathematical models of tumors [17]. The urgency of an integrated approach merging in vivo experiments and in silico representations to obtain more powerful descriptive and predictive models is also emerging: for instance, the integration of microfluidic devices and computational modeling to better study vascularization dynamics in cancer [18].…”

mentioning

confidence: 99%