Xu Cao

All Publications

• Clinical Trial in a Dish for Space Radiation Countermeasure Discovery. Life sciences in space research Cao, X., Weil, M. M., Wu, J. C. 2022; 35: 140-149

  Abstract

  NASA aims to return humans to the moon within the next five years and to land humans on Mars in a few decades. Space radiation exposure represents a major challenge to astronauts' health during long-duration missions, as it is linked to increased risks of cancer, cardiovascular dysfunctions, central nervous system (CNS) impairment, and other negative outcomes. Characterization of radiation health effects and developing corresponding countermeasures are high priorities for the preparation of long duration space travel. Due to limitations of animal and cell models, the development of novel physiologically relevant radiation models is needed to better predict these individual risks and bridge gaps between preclinical testing and clinical trials in drug development. "Clinical Trial in a Dish" (CTiD) is now possible with the use of human induced pluripotent stem cells (hiPSCs), offering a powerful tool for drug safety or efficacy testing using patient-specific cell models. Here we review the development and applications of CTiD for space radiation biology and countermeasure studies, focusing on progress made in the past decade.

  View details for DOI 10.1016/j.lssr.2022.05.006

  View details for PubMedID 36336359

• Looking on the horizon; potential and unique approaches to developing radiation countermeasures for deep space travel. Life sciences in space research Bokhari, R. S., Beheshti, A., Blutt, S. E., Bowles, D. E., Brenner, D., Britton, R., Bronk, L., Cao, X., Chatterjee, A., Clay, D. E., Courtney, C., Fox, D. T., Gaber, M. W., Gerecht, S., Grabham, P., Grosshans, D., Guan, F., Jezuit, E. A., Kirsch, D. G., Liu, Z., Maletic-Savatic, M., Miller, K. M., Montague, R. A., Nagpal, P., Osenberg, S., Parkitny, L., Pierce, N. A., Porada, C., Rosenberg, S. M., Sargunas, P., Sharma, S., Spangler, J., Tavakol, D. N., Thomas, D., Vunjak-Novakovic, G., Wang, C., Whitcomb, L., Young, D. W., Donoviel, D. 2022; 35: 105-112

  Abstract

  Future lunar missions and beyond will require new and innovative approaches to radiation countermeasures. The Translational Research Institute for Space Health (TRISH) is focused on identifying and supporting unique approaches to reduce risks to human health and performance on future missions beyond low Earth orbit. This paper will describe three funded and complementary avenues for reducing the risk to humans from radiation exposure experienced in deep space. The first focus is on identifying new therapeutic targets to reduce the damaging effects of radiation by focusing on high throughput genetic screens in accessible, sometimes called lower, organism models. The second focus is to design innovative approaches for countermeasure development with special attention to nucleotide-based methodologies that may constitute a more agile way to design therapeutics. The final focus is to develop new and innovative ways to test radiation countermeasures in a human model system. While animal studies continue to be beneficial in the study of space radiation, they can have imperfect translation to humans. The use of three-dimensional (3D) complex in vitro models is a promising approach to aid the development of new countermeasures and personalized assessments of radiation risks. These three distinct and unique approaches complement traditional space radiation efforts and should provide future space explorers with more options to safeguard their short and long-term health.

  View details for DOI 10.1016/j.lssr.2022.08.003

  View details for PubMedID 36336356

• Acoustic Fabrication of Living Cardiomyocyte-based Hybrid Biorobots. ACS nano Wang, J., Soto, F., Ma, P., Ahmed, R., Yang, H., Chen, S., Wang, J., Liu, C., Akin, D., Fu, K., Cao, X., Chen, P., Hsu, E. C., Soh, H. T., Stoyanova, T., Wu, J. C., Demirci, U. 2022

  Abstract

  Organized assemblies of cells have demonstrated promise as bioinspired actuators and devices; still, the fabrication of such "biorobots" has predominantly relied on passive assembly methods that reduce design capabilities. To address this, we have developed a strategy for the rapid formation of functional biorobots composed of live cardiomyocytes. We employ tunable acoustic fields to facilitate the efficient aggregation of millions of cells into high-density macroscopic architectures with directed cell orientation and enhanced cell-cell interaction. These biorobots can perform actuation functions both through naturally occurring contraction-relaxation cycles and through external control with chemical and electrical stimuli. We demonstrate that these biorobots can be used to achieve controlled actuation of a soft skeleton and pumping of microparticles. The biocompatible acoustic assembly strategy described here should prove generally useful for cellular manipulation in the context of tissue engineering, soft robotics, and other applications.

  View details for DOI 10.1021/acsnano.2c01908

  View details for PubMedID 35671037

• Generation of three induced pluripotent stem cell lines from hypertrophic cardiomyopathy patients carrying MYH7 mutations. Stem cell research Cao, X., Jahng, J. W., Lee, C., Zha, Y., Wheeler, M. T., Sallam, K., Wu, J. C. 2021; 55: 102455

  Abstract

  MYH7 heterozygous mutations are common genetic causes of hypertrophic cardiomyopathy (HCM). HCM is characterized by hypertrophy of the left ventricle and diastolic dysfunction. We generated three human induced pluripotent stem cell (iPSC) lines from three HCM patients each carrying a single heterozygous mutation in MYH7, c.2167C>T, c.4066G>A, and c.5135G>A, respectively. All lines expressed high levels of pluripotent markers, had normal karyotype, and possessed capability of differentiation into derivatives of the three germ layers, which can serve as valuable tools for modeling HCM in vitro and investigating the pathological mechanisms related to MYH7 mutations.

  View details for DOI 10.1016/j.scr.2021.102455

  View details for PubMedID 34352619