Development Story

Organ culture system
Episode 1
To study the site
Dive
Episode 2
Difficult beyond our imagination
Episode 3
Organ perfusion
to many researchers
Episode 4
Our feelings to deliver

Episode 1

Dive to the research site

​"Can you make a container for creating organs in vitro?"

 

When we received the first offer, we decided that we would start developing, thinking that we could make use of our technology for small culture devices.

 

 

 

Thinking that "This problem cannot be solved without jumping into the actual research site", I managed to persuade the president to do organ perfusion research as a research student at the Institute for Advanced Biomedical Science, Tokyo Women's Medical University It was decided.

 

As a researcher, I started the days of developing devices while researching, and as a manufacturer developer, checking the "desired functions" and "usability".

 

 

 

When I entered the laboratory, it was the first time I had ever seen anything from equipments and techniques, animal management to anesthesia techniques that I had never seen in the company's development room. At first, the days of training in which I was able to observe the technique of extracting tissue from animals from behind a researcher's teacher were repeated many times.

 

 

I was wondering if I would be able to do something like this, but thanks to the patiently instructing teacher, I gradually learned the technique and managed to extract organs from animals with my own hands. It has become possible to extract and perform perfusion.

 

Episode 2

Difficult beyond our imagination

The research involved collecting the rat skeletal muscle tissue of the femur called the vascular bed with arteriovenous tissue, perfusing and culturing it with a perfusion device, and laminating a myocardial sheet on it. In an actual experiment, one week before the start of perfusion, blood vessels were processed in the rat's body and then perfusion of the excised muscle tissue was started (up to this stage of preparation), and then cell sheets were laminated to form myocardial tissue. Was made (this is the main experiment), and this was the experiment at that time (Note 1).

 

In the beginning, the preparation was not enough, contamination occurred in the preparation stage, the organs that could not be removed due to the inability to insert blood vessels could not be perfused, and the days when it was difficult to proceed to the main experiment continued. It was I felt literally how hard it was to prepare for each perfusion experiment and how much time and effort it took.

 

The hardest part was how to fix a soft organ in a hard container. In particular, blood vessels are slippery anyway. In the continuous situation that we can understand only after actually performing organ perfusion, we devised "How about such a structure", "Let's use a slightly softer material" etc. one by one, and returned to the company and made a prototype. Then, in the next week, I will try it in the laboratory and find the next task. "If you use this material, it may be easier to fix soft organs," he says. This time, the trial and error process was repeated, saying, "The softness of the material was good, but it melted because it could not withstand sterilization."

 

At that time, I reported the experimental results on Mondays and immediately designed the countermeasures myself, but I was greatly assisted by colleagues in the company who made prototypes quickly. Occasionally, there was a week where I could complete the design on Monday, finish the prototype in two days, and use that week for actual testing. Everyone was already crazy. It took more than half a year for the success rate of starting organ perfusion to exceed 50%, but now I can manage organ perfusion.

 

Note 1 See paper for details:

Sekine H, Shimizu T et al. In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels. Nat Commun, 2013.

Available from: https://www.nature.com/articles/ncomms2406

 
​培養チャンバーのチューブセッティングの様子

Episode 3

Organ perfusion to many researcher

After that, as a graduate student at the Tokyo Women's Medical University as a graduate student, I actually conducted research on the subject of perfusing rat thigh skeletal muscle in vitro. In addition, a new project (Note 2) was adopted, and it was decided that the organ perfusion device could be used in the experiment of the project.

Researchers other than myself will also be using organ perfusion devices, and in addition to the parts I have felt so far, "complex initial setting" "difficult to hold soft organs and blood vessels" "small lab We received many opinions such as "It is better to be as compact as possible to install it inside." "I don't know if the temperature around the actual organs can be controlled accurately."

If you dig deeper into the opinions that "the initial setting is complicated" and "it is difficult to connect soft organs and blood vessels", the selection of tubes and pumps is complicated, and the connection of blood vessels cannot be done well. Then, I found that it took a lot of time and effort at the setting stage before I tried the challenging tasks such as perfusing the organs to make the organs.

Similarly, the opinion that "it is better to be as compact as possible to install it in a small laboratory" and "I do not know whether the temperature near the actual organs can be controlled accurately" is the same as that of our small culture device. It seemed possible to solve it by applying the technology.

Therefore, I began to have a strong desire to “reduce the hurdles to start organ perfusion and spend time on subsequent research”, and complete an “organ culture system” that everyone can use. I decided

*2 AMED business “Medical device/system research and development business that realizes future medical care” Development of functional biological tissue manufacturing technology by three-dimensional modeling / Research and development of functional three-dimensional organ production technology using cells / Cell sheet engineering Development of innovative solid organ manufacturing technology based on

 
 

Episode 4

Our feelings to deliver

The aim of the " organ culture system " is a device that can be widely used by everyone and that can be used as a tool for organizing new research ideas.

In order to eliminate the hurdles of "complex initial setting" and "difficult connection of soft organs and blood vessels", all tubes that connect the medium bottle to blood vessels are set as a " tube set " and it is necessary to select tubes Lost.

In addition, the pump that delivers liquid into the blood vessel is large, and its characteristics are various, so selection was complicated, so we also made a set.

The "organ chamber " that actually holds the soft organ is customized for each organ to be perfused. Since the characteristics and size differ depending on the organ, it is possible to customize it, and it is quickly customized using know-how to securely hold a soft organ and know-how to connect a tube to a blood vessel of about 1 mm. In the future, it will be possible to consider making it disposable by mass production (with a track record in the laboratory).

In addition to custom-made products, we have added a lineup of chambers for rat small intestine and rat skeletal muscle in response to everyone's requests (2020.2.25 added).

In addition, in order to eliminate the hurdles of installation and temperature control, such as "it is better to be as compact as possible for installation in a small lab", "I do not know whether the temperature near the actual organ can be controlled accurately", The " bioreactor unit " enables highly precise temperature control. It is possible to control the temperature from 4°C to 37°C by the setting obtained by measuring the temperature around the actual organ in the verification. For temperature control, we apply 25 years of know-how of our Stage Top® Incubator Thermoplate®.

It's more difficult than the imagination that the developer could see for the first time by actually jumping into the research site and actually performing an experiment. In order to overcome this, we have made steady improvements and built up the basic technology of the "organ culture system". After that, we continued the development aiming to provide organ perfusion to many people, and lowered the hurdle for organ perfusion start with the three configurations of "culture chamber", "tube set" and "bioreactor unit".

Why don't you start organ perfusion research with an "organ culture system" filled with a lot of developer's thoughts that "I want people to widely use it and perform organ perfusion as a research tool"?

​ Product manager: Kazunori Sano

Tokai Hit Development Co., Ltd.

Organ Culture System product manager

Ph.D. (medicine)

Biography:

Completed Department of Applied Life Sciences, Tokyo University of Agriculture and Technology

Joined Tokai Hit Development Division (at that time)

Tokyo Women's Medical University

Completed 44th term of biomedical curriculum

Tokyo Women's Medical University

Completed doctoral degree in the field of substitute organs in the Department of Advanced Biomedical Sciences

2012 

 

2012 

 

2012 

                             

2018 

                              

TERMIS-World (2018 Kyoto)

TERMIS-EU (2018 Swiss),

TERMIS-AP (2017 Taiwan),

Japan Regenerative Medicine Society (2015-2018)

​Main presentation society:

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