Reviews

Professor Matt Kutys gave a talk on the afternoon of Oct 27th, 2022. He identifies himself as a biologist who uses engineering tools to make micro physiological systems that would allow deeper inquiries into biological questions. His research gave a clear idea of how microphysiological systems can advance our understanding of biology.

His research on tuberculosis highlights why it is necessary to develop microphysiological systems and how powerful they can be. Tuberculosis is caused in human by a bacterium called Mycobacterium tuberculosis. Once contracted, M.Tuberculosis can be either confined in granulomas or spread further, leaving necrotic tissues behind. It is unclear what parameters dictates granuloma formation or spreading. Unfortunately, animals are relatively less susceptible. This limits the research on tuberculosis as researchers have to rely on human biopsies. The development of an in vitro microphysiological system modeling the development of tuberculosis will allow researchers to use human cells and modulate various parameters to investigate the mechanism of tuberculosis development.

Throughout his presentation, he showed various live images of flow inside vasculature, cell migration, vasculature collapsing, etc. Such visualization is very helpful for scientists to understand what is going on and gain insight into the underlying mechanisms, which would lead to meaningful hypotheses and discoveries. Such live imaging is difficult, if not impossible, in animal models.

Also, microphysiological systems allow control of variables that are hard to modulate in animal models or traditional 2D cultures. The professor presented a project on mechanobiology of vasculatures. He controlled the speed of flow inside microphsyological vasculatures and investigated changes in cadherin interactome, notch activation, etc.

Overall, microphysiological systems provide a powerful tool for biological and biomedical research. The use of human cells provide a human relevant platform. Compatibility with live imaging helps researchers understand the biological phenomena unraveling in the system. Controllability and high-throughput nature of these systems enable rapid sweep of parameter space while enabling perturbations difficult, if possible at all, in vivo, such as mechanical perturbations. It would be exciting to witness the development of microphysiological systems and how it changes biology and biomedical research.

In December 2021, Professor Masaya Nakamura and Professor Hideyuki Okano, both at the Keio University Hospital, successfully transplanted neural progenitors derived from induced pluripotent stem cells (iPSCs) into spinal cord injury patients (link). Treating spinal cord injury using stem cells have been extensively tested using animal models. The professors at the Keio University Hospital managed to finally apply the technology to humans.

We take for granted a lot of things and one of them is our own body. Even the slightest damage like a cut in the finger reminds us that we should appreciate every inch of our body, although we forget soon after taking off the band-aid. However, what if the damage is irreversible? For example, an amputated finger, severed spinal nerves, or a balding head. This can happen to anyone, including myself and my loved ones. I envision a world where such injuries/diseases are simply cured by replacing it with a new one, a vision shared by others in the name of regenerative medicine.

To rebuild our organs, it makes sense to start by studying how it was built in the first place. To this end, I have joined professor Jianping Fu’s research group to study embryonic development. Currently, I am developing an in vitro hESC model for the nervous system development. In theory, the knowledge of the early development can be utilized for regeneration of the nervous system. However, specifically of how the knowledge can be used is still unclear to me. Thus, I plan to review the followings: 1) the current knowledge and knowledge gaps in the development of the nervous system, 2) the anatomy and physiology of the fully developed nervous system, 3) status quo of the treatment and regeneration of the nervous system. Sufficient knowledgeability on these three fronts will enable me to identify possible junctions of embryology and regenerative medicine.

Specific aspects I will review in the three fronts are as follows:

1. The current knowledge in development of the nervous system
   • Formation of the neural tube
   • AP patterning of the neural tube
   • DV patterning of the spinal cord
     • Mechanism of Shh signaling
     • Mechanism of dorsalizing signals such as BMPs and Wnts
     • Pattern scaling
   • Development of the brain (Forebrain ~ hindbrain)
   • Neurogenesis
2. The anatomy and physiology of the fully developed nervous system
3. The Status quo of the treatment and regeneration of the nervous system