"The expression of MLLT3 gene is the key to determining the self-renewal ability of hematopoietic stem cells."
Ding Mian stood in front of the operating table filled with various equipment, pointing to the bright red in the rectangular petri dish in front of him, and introduced it eloquently.
"This is the result of our hard work for more than half a year, real artificial blood."
"We took epithelial cells from more than ten experimental mice and introduced a combination of four factors, Oct4, Sox2, Nanog and LIN28, to induce all of them into induced pluripotent (iPS) stem cells."
"Following this, five special transcription factors were introduced to induce the iPS stem cells into hematopoietic stem cells."
"Up to this point, the systematic laboratory training I have received is just basic operations, which are quite easy. I think back then, when I was in the doctoral laboratory, I had done such experiments countless times, so I was so familiar with them. Flow, that's all..."
"Ahem~" Tang Que stood behind him, coughed twice, and said expressionlessly: "Let's get to the point."
"Yes, yes, the focus is on the MLLT3 gene. We used gene editing technology to insert the active MLLT3 gene into the hematopoietic stem cells. Subsequently, the hematopoietic stem cells in the culture dish multiplied at least 20 times and showed no tendency to stop."
"We have transplanted these hematopoietic stem cells into mice and tested them. The mice developed a fully functional and long-lasting blood system, in addition to all the normal components of the immune system, with no signs of leukemia or any other blood disease. This way The results are enough to confirm the success of the experiment.”
"However, this is only half the battle."
There were about twenty staff members in white coats standing around, their eyes shining, listening attentively.
After being reminded, Ding Mian stopped talking and went straight to the topic.
“Since we wanted real artificial blood in addition to hematopoietic stem cells, we quickly started on the next step.”
"This has to talk about another H gene that controls blood type."
"It is well known that the antigens expressed on the red blood cell membrane determine the blood type, the most important of which is the ABO blood group system."
"Type O red blood cells do not contain A and B antigens, but the plasma contains anti-A and anti-B antibodies; type A red blood cells have type A antigens on their membranes, and plasma contains anti-B antibodies; type B red blood cells have type B antigens on their membranes , lAnd the plasma contains anti-A antibodies."
"Type AB red blood cells have type A and type B antigens on their membranes, but no antibodies are present in the plasma. Any red blood cells of the ABO blood group can be accepted."
"If the wrong blood type is entered and the antigens on the surface of red blood cells meet the corresponding antibodies in the serum, A versus A or B versus B, blood coagulation will occur immediately, which can lead to death in severe cases."
"The H gene can control the synthesis of H antigen. H is the antigen of Hh, the second largest blood group system. A and B are the antigens of the ABO blood group system. The two systems are inherited independently, but the H antigen is the precursor substance of the ABO blood group. It has A, The B antigenic sugar group needs to be connected to the H antigen in order to be converted into A and B antigens and show the corresponding A, B, and AB phenotypes."
"If the expression of the H gene is missing in hematopoietic stem cells, there will be no H antigen in the blood, and A and B antigens will not be produced. This means that this blood can be transfused into any ABO blood type and is truly universal blood. .”
"So, while inserting the active MLLT3 gene fragment, we also inhibited the expression of the H gene, so that the genetically modified hematopoietic stem cells can be induced to generate universal artificial blood that can be delivered to humans."
"Of course," he smiled: "Since there are hundreds of antigens on the human red blood cell membrane, some rare blood types are not included."
There was a burst of knowing chuckles from all around.
A young man in his early 20s said with excitement: "This is the legendary Bombay blood. This is a very rare blood type. I didn't expect that we could synthesize it in the laboratory. This is definitely a shocking breakthrough in synthetic biology." .”
Everyone else nodded and praised him all the time.
"Bombay blood was discovered in Mumbai, India, in the 1950s. It is comparable to the legendary dinosaur blood in China. It seems that there are only more than a hundred cases in the country. It is of great significance!"
"This blood can be transfused to most people regardless of popular blood types. If used in large quantities, it can greatly improve the storage and transportation of blood banks."
"From now on, our country will never be short of food. It's exciting to think about it."
"This is the meaning of our work. To personally change the world, what job can be as fulfilling as that?"
"Yes, even if I have been working overtime during this period, it is still worth it."
"But we are only generating it in the laboratory, the real difficulty is yet to come."
"That's right." Ding Mian took over the conversation and said confidently: "In fact, many of the prerequisite theories for artificial blood are quite mature, and it is not particularly difficult to develop them in the laboratory."
“In the past few years, teams at home and abroad have been trying to generate hematopoietic stem cells in vitro in the laboratory. Of course, some teams have indeed made progress, but they only stay in the laboratory stage, and there is no further progress after animal experiments. "
"We can go one step further and generate real artificial blood in the laboratory, which means we have gone further than others."
"However, there is still one big boss on this difficult road, which is mass production."
"We are an enterprise. If the products we develop cannot be commercialized and mass-produced, it is meaningless."
Having said this, Ding Mian raised four fingers, and his slightly childish face finally turned serious.
"Let me summarize, there are five stages in the conversion of human epithelial cells into artificial blood."
“The first stage is the induction period, which is 0-8 days after the introduction of exogenous genes. During this period, epithelial cells will begin to be induced into iPS stem cells.
"The second phase, the differentiation period after this, about 7 to 10 days, is when the iPS stem cells transform into hematopoietic stem cells."
"The third stage involves genetic modification of hematopoietic stem cells, mainly MLLT3 and H genes. This technology is very mature and can be completed within 3 days.
"The fourth stage, about 15 days after cell fate determination, is the expansion period. At this time, the newly generated hematopoietic stem cells proliferate in large numbers and have transcriptomes and long-term self-renewal capabilities similar to normal adult hematopoietic stem cells. The length of this time Depends on the number of hematopoietic stem cells required."
"In the fifth stage, three special factor combinations are introduced again, and the hematopoietic stem cells are officially transformed into universal blood in the culture dish, which takes about a week."
"When the conversion is complete, we can collect the blood in the petri dish and store it for use."
"These five processes don't seem complicated, but if they are applied directly to biofactories without improvement, it is likely to turn into a complete disaster during mass production."
"Next, our first priority is to do our best during the clinical trial period to improve the production process so that it can be successfully commercialized and mass-produced at an affordable cost."
"In this way, the artificial blood project can truly succeed, and our efforts over the past six months will be meaningful."
"Are you ready to overcome the next bigger difficulty?"
Ding Mian raised his clenched fists and shouted loudly.
"Ready!"
Everyone roared in unison.
Their eyes shot out with gleams of light, and their expressions were extremely excited, like a group of warriors getting ready to go to the battlefield.
Seeing everyone walking out of the laboratory in high spirits, Tang Que looked at Ding Mian and said with approval.
"What you just said was very good, and your mobilization skills are also good. You are as good as me."
Ding Mian chuckled and said, "Of course, I learned from you. Can the effect be bad?"
Tang Que smiled slightly and was about to say something modest.
But I heard Ding Mian continue: "Everyone in the biology laboratory has been conditioned by your PUA. I just learned how to turn it on and off, and the effect is natural."
He squeaked, snapped his fingers, and said triumphantly: "Brother Que, if not you are the boss, the effect of this brainwashing magic is really amazing. When I first saw it, It was like a pupil earthquake, I never thought that the laboratory could still be managed and played like this."
Tang Que's expression changed and turned as dark as the bottom of a pot.
A flash of light flashed in his eyes, and he said calmly: "Okay, you can report to General Wei yourself later."
After saying that, he turned around and left.
"Ah, I was wrong, Brother Que, you shouldn't be so insignificant." Ding Mian suddenly panicked and hurriedly caught up.
"Mr. Wei is such a big shot. If you weren't there when I met him, I would be really nervous."
Tang Que touched his chin speechlessly, turned around and said, "You have been here for more than half a year, why are you still like this? You are not stable at all."
"Did you develop this artificial blood technology by yourself? If it hadn't been for the company's platform, if it hadn't been for the hard work of colleagues, and if it hadn't been for President Wei's presence, would you have achieved such results as soon as you entered the company?"
He shook his head and said, "You are raising your tail so quickly? When you can really develop something new, no matter how proud and complacent you are, I will not care about you, I will only cheer for you. Now." , just save it."
"Originally, I wanted you to show your face in front of President Wei this time and gain impression points, forget it!"
"I'll do this report myself."
Ding Mian's face fell instantly. He pursed his lips and muttered in his heart before returning to his seat.
He is an only child with no brothers or sisters. Tang Que has always been with him when he was lonely, so he subconsciously treats him as an elder brother. After a short period of time after starting work, he has not adapted to this hierarchical relationship between superiors and subordinates. .
So after being scolded by Tang Que, he didn't feel any resistance. Instead, he knew that the other party's words were good words.
"Okay, isn't it just a matter of keeping a low profile and being insignificant? No one understands this better than me."
He turned on the computer, twirled his fingers, turned all his emotions into motivation, and devoted himself to selfless work.
****
Kunming First People's Hospital, Department of Hematology.
Early in the morning, Liu Zhengming walked to the office and saw someone waiting at the door.
"Hello, Director Liu. I am Jia Qing, a clinical researcher at Sanqing Group. I recently have a clinical project on blood products, and I would like to conduct a clinical trial with the hematology department." The visitor is a young and energetic guy with a very polite attitude. .
"Oh, people from Sanqing, the young man is quite young. Come in." Liu Zhengming opened the door and walked in.
Jia Qing quickly made two cups of tea, handed over one cup, and then sat down opposite.
"Okay, since you are a researcher at Sanqing, just follow the procedures." Liu Zhengming said calmly.
"First tell me carefully what kind of clinical trial it is." He picked up the tea cup and blew hot air gently on the rim of the cup.
"It is a clinical project of artificial blood. We use human epithelial cells to induce differentiation into hematopoietic stem cells, and use genetic technology to remove the antigens on red blood cells to obtain artificial blood without the three antigens A, B, and H."
"Success has been achieved in experimental animals such as mice and macaques..."
Jia Qing felt a little nervous and pretended to be calm.
He is an employee who just joined the company this year. The first project he followed up on when he joined the company was so important, so he was a little uneasy.
"Huh?" Liu Zhengming was about to drink tea. He quickly put down the cup and said with a shocked look on his face: "Wait, you are talking about artificial blood?"
"iPS stem cells are induced to differentiate into hematopoietic stem cells, and then universal artificial blood is produced outside the body?"
Jia Qing nodded and handed over the project introduction materials he was holding tightly in his hand.
Liu Zhengming stopped drinking tea. He took the information and browsed it carefully as if he was facing a formidable enemy.
While watching, he slapped his thigh fiercely.
When he was about to finish reading, he suddenly looked up and asked in disbelief: "That's not right. Why didn't you publish a paper for such an important achievement?"
"This project is definitely a top-level paper. It covers science, cells, and nature. It must be published casually. Don't you want to publish it?"
Jia Qing curled his lips and whispered: "Because we are at odds with foreign academic circles, our findings will no longer be published in foreign academic journals."
Liu Zhengming suddenly felt itchy: "How can this be done? How can such an important experimental result not have a paper? If it cannot be published in foreign publications, just publish it in China. Isn't it possible that domestic publications can't do it?"
Jia Qing was stunned for a moment, scratched his head and said, "This seems to have been posted on the Sanqing internal forum."
Liu Zhengming said sadly: "You are too stingy. Is it appropriate not to show such important results to others?"
He angrily said: "Who is your leader? I want to respond to him. No, I have to respond to President Wei online."
Jia Qing smiled and said: "Okay, Director Liu, I will convey it to the leader for you. You should first see how this clinical trial is carried out?"
"Should we first recruit some volunteers and receive two small blood transfusions four months apart, and then monitor them closely to see if there are any adverse reactions in the body?"
Liu Zhengming nodded: "That's about it. At least 10 subjects must participate in the first batch, two small blood transfusions of 5-10ml, one with standard donated blood, and one with laboratory-cultured artificial blood. To determine the lifespan and response of artificial blood in the human body."
"Very good, artificial blood is also marked with medical radioactive substances, so that we can better monitor its whereabouts in the human body and understand how long the artificial blood survives in the body."
"However, you need to be bolder in choosing this person." He frowned and slammed the table. "This is rare Bombay blood. It is in short supply everywhere."
Jia Qing suddenly trembled with fright.
Li Zhengming didn't even look at him, and took out his mobile phone to make a call.
"Hello, Sioux Blood Center?"
“How many of you have Bombay blood?”
"I need a list of Bombay Blood and Bombay Blood-like personnel."
"There's a major clinical trial of artificial blood here that they need to take part in."
(End of chapter)
