Tumor spheroid connected to microengineered vasculature in a 3D hydrogel by Jungho AhnThe cost of drug development has dramatically increased during the last several decades due to the inefficiency of current pre-clinical drug screening models. Major disadvantages of conventional drug screening models are (i) the dissimilarity between two-dimensional (2D) in vitro cell culture systems and in vivo models, and (ii) the phylogenetic difference between human and animal models. Advanced 3D cell culture model systems have demonstrated advantages in providing more physiologically relevant conditions and more predictive ability. The integration of microfluidic technology and cell biology research has recently reached a significant milestone with the development of “organ-on-a-chip” technologies that reconstitute the organ-level in vivo characteristics. Developing improved in vitro models through these innovative technologies will promote fundamental cancer research and accelerate drug discovery and clinical translation.
A tumor microenvironment (TME) consists of a heterogeneous mix of cellular and non-cellular components including surrounding blood vessels, immune cells, fibroblasts, cancer stem cells and extracellular matrix (ECM). The elucidation of the complex cellular interactions within the TME remains one of the main challenges in the treatment of cancer. It has become increasingly recognized that the study of human cancer cannot be simplified to homogeneous collections of neoplastic cells, but must instead be studied as complex multicellular systems to properly reflect interactions between malignant and non-malignant cells. This interplay between the tumor and the stroma has been recognized as a characteristic property of the TME, and this paradigm is now considered to be a hallmark of cancer biology. Animal models are conventionally the gold standard for screening cancer therapeutics because of their capabilities to sustain the complex TME. However, accurate mimicry of human tumorigenesis is extremely difficult, questioning the usefulness of existing in vivo models for therapeutic efficacy translation. Meanwhile, recent advancements in the microengineering of TME using organ-on-a-chip technologies have enabled the development of pathophysiologically relevant human tumorigenesis models. In this review, we describe the most recent existing organ-on-a-chip approaches to study the tumor and its interactions with the surrounding microenvironments including stromal cells, vasculature, and non-cellular components. We also highlight the applications of these leading-edge technologies to cancer drug/nanomedicine prescreening, and discuss the current challenges and future directions for these technologies.
In collaboration with Prof. Noo Li Jeon, we engineer microvascularized tumor environment models that allow unprecedented mechanistic examination of tumor progression and metastasis and will be used for anticancer drug prescreening applications.
Ahn J*, Koo DJ*, Kim DH*, Lim J, Park T, Lee J, Ko J, Kim S, Kim JJ, Kim M, Kang KS, Min DH, Kim SY, Kim Y*, and Jeon NL*, 3D microengineered vascularized tumor spheroid for drug delivery and efficacy testing (2019) Under review.
Ahn J, Lim J, Jusoh N, Park T, Kim Y, Kim J, and Jeon NL, Microengineered vascularized tumor microenvironment in a bone-mimetic hydroxyapatite/fibrin composite (2019) Biofabrication. Under revision.
Ahn J, Sei YJ, Jeon NL, and Kim Y, Tumor microenvironment on a chip: the progress and future perspective (2017) Bioengineering 4 (3): 64 (Link).