(7g) Organ-on-a-Chip and 3D-Printing Technologies: Applications in Nephro-Cardiovascular Diseases

Approximately 26 million Americans are diagnosed with kidney diseases, with an estimated collective cost to the healthcare system of over $40 billion. Chronic Kidney Disease (CKD) is considered the most fatal and expensive to treat disease since it leads to kidney failure and the only solution may be kidney transplantation. Although organ transplantation has saved millions of patient lives, significant challenges remain, such as the high cost of kidney donor transplant and the long waiting lists for donor organs. In addition, patients who receive a kidney transplant are subject to lifelong anti-rejection medications, which are accompanied with lifelong side-effects such as increased rates of infections, and diabetes. Thus, it is necessary to engineer methods for optimizing organ transplantation and for kidney therapeutics, which can be applied to personalized medical treatment based on individual physiological conditions of each patient.

My past and current research interests focus on the development of new tools to identify new biological targets involved in vascular diseases (1-7). Vascular involvement is a primary cause for acute renal failure (ARF) or acute kidney injury (AKI) which can result in prolonged loss of kidney function and vascular perfusion. Therefore, a deeper understanding of the complex bidirectional and interdependent interactions between the vascular and renal compartments in pathophysiological conditions is needed. My long term vision is the integration of biomedical and technological approaches within a single framework for potential translational and therapeutic purposes of nephro-vascular diseases. Such a vision requires a multidisciplinary research program which encompasses: (i) Organ-on-a-chip technology to build multicellular level functional units of kidney through micro-engineering approaches. This strategy will involve a functional biomimetic microfluidic unit that captures both the microvascular and renal tubular systems, where increasingly complex architectures with tunable biophysical and biochemical properties will be studied. This in vitro platform is ideal to mimic kidney filtration (GFR) and microvascular function (kidney-on-a-chip) and to identify novel drugs/targets involved in acute or chronic renal-vascular diseases. (ii) Engineering stem cell therapy technologies to model the appropriate cells involved in nephro-vascular diseases within the kidney-on-chip and establish such cells for regenerative applications. Engineering functional stem cells (iPS-driven cells/adult stem cells) in combination with molecular biology strategies including CrispR technology will be used to investigate the genetic basis for ARF. Additionally, the differentiated functional cells can be applied for cell therapy purposes needed for personalized medical treatment of CKDs. (iii) 3D printing technology to build functional organ for transplantation. Integration of organ-on-a-chip and stem cells technologies with 3D printing technologies will enable the 3D-printing autologous organ for transplantation in animal disease models, such as spontaneously hypertensive rats (SHR), which are developing abnormalities in vascular-renal functionality.

Aside from the exciting and challenging intellectual aspects of the technologies of organ-on-a-chip, stem cell therapy and 3D printing in treating nephron-vascular diseases, I view them as platforms to address hurdles in developing novel therapeutics for organ diseases and engineering whole organs.

References

1. Alimperti, S., Lei, P., Tian, J., and Andreadis, S. T., “A novel lentivirus for quantitative assessment of gene knockdown in stem cell differentiation”, Gene Therapy, 19, 1123-32 (2012).
2. Alimperti, S., Wen, Y., Lei, P., Tian, J., Campbell, A., and Andreadis, S. T., “Serum-Free Spheroid Culture maintains high proliferation and differentiation potential of MSCs”, Biotechnology progress, 30, 974-983 (2014).
3. Alimperti, S., You, H., George, T., Agarwal, S., Andreadis, S. T., “Cadherin-11 regulates both mesenchymal stem cell differentiation into smooth muscle cells and contractile function in vivo”, Journal Cell Science, 127, 2627-2638 (2014).
4. Alimperti, S., Andreadis, S. T., “CDH2 and CDH11 act as regulators of stem cell fate decisions”, Stem Cell Research, 14, 270-282 (2015).
5. Row, S., Liu, Y., Alimperti, S., Agarwal, S., Andreadis, S. T., “Cadherin-11 is a novel regulator of extracellular matrix and tissue mechanics”, Journal of Cell Science, 129, 2950-2961 (2016).
6. Alimperti, S., Mirabella, T., Bajaj, V., Polachek, W., Pirone, D., Duffield, J., Assoian, R., Chen, C.S., “A 3D biomimetic vascular model reveals a RhoA, Rac1, and N-cadherin balance in pericyte-regulated barrier function” (provisional accepted in PNAS).
7. McCurley, A., Alimperti, S., et.al., “Inhibition of avb5 integrin leads to a pericyte-dependent attenuation of vascular permeability and protects against renal ischemia-reperfusion injury”, Journal of the American Society of Nephrology, 2017

Teaching Interests:

The opportunity to educate future generations of chemical engineers is my principal motivation for pursuing an academic career in Chemical and Biological Engineering departments. During my Ph.D. in chemical and biological engineering department at State University of New York at Buffalo and as well, during my postdoctoral training at Wyss Institute at Harvard University, I established expertise in engineering fundamentals, which I applied them to develop new biomedical engineered tools and ultimately, to investigate new biological questions. My philosophy on teaching in a chemical engineering department is built from this experience, and in the laboratory, I will emphasize in integrating engineering design principles with biology. In the classroom, my major focus will be to establish primary principles that build intuition to enable rational problem solving in biological sciences independently of a student’s chosen career path. Establishing a solid background in chemical engineering courses including mass and heat transport (Transport phenomena), unit operations, tissue engineering, material engineering, and chemistry, I would be comfortable teaching similar or related courses at the undergraduate or graduate level. Finally, one of my key interests is in participating in senior design projects designed to introduce undergraduates to department faculty and their research.