HP Work Summary
Introduction: From Society, To Society

This project focuses on the severe global health challenge of liver fibrosis, cirrhosis, and even end-stage liver disease. With engineered exosomes (EVs) as the core therapeutic technology, we have built an integrated HP closed loop of "social demand input → social interactive co-creation → social feedback of achievements". This is our fundamental path to connect science and society, and also a key pillar to promote exosome therapy from a "technical concept" to a "patient-accessible solution".

Originating from Real-World Needs: Taking Social Pain Points as the "Calibrator" for Scientific Research

If we ignore the public’s cognitive gaps in liver disease, the diagnostic and therapeutic bottlenecks faced by clinicians, and the patient demands that cannot be fully covered by medical record data, even the most advanced technology will eventually become an unimplementable theory.
We conducted surveys among the public to identify their cognitive blind spots regarding "reversibility of liver fibrosis" and "exosome therapy", laying the groundwork for future knowledge dissemination. We engaged in in-depth dialogues with clinicians to understand industry dilemmas such as "liver sources only meeting 10% of demand" and "limited efficacy of single therapies", obtaining professional guidance for technological iteration. Furthermore, we empathized deeply with patients and their families to uncover "hidden predicaments" that cannot be quantified— the financial burden of daily medication, the physical and mental exhaustion from repeated hospitalizations, and the emotional anxiety of worrying about affecting family members. These demands collectively defined the rigid bottom line of "safety, efficacy, and affordability" for our research and development. At the same time, we proactively aligned with ethical standards and regulatory frameworks to ensure the project complies with regulations from the very beginning. It is this multi-dimensional insight into needs that ensures our exosome research is never "innovation for innovation’s sake", but rather a "targeted solution" to real social problems.

Integrating into Co-Creation with Diverse Wisdom: Turning External Feedback into a "Calibrator" for Technology

The "cognitive limitations" of research teams are major obstacles to technology translation. To address this, our "social interactive co-creation" segment is designed to open a "window of diverse perspectives" for the project. Through the collision of cross-boundary wisdom, our technical solutions can be aligned closely with real clinical needs.
We rejected the limitations of traditional academic exchanges and designed pathways for in-depth participation by different groups:

Cooperating with teachers and students from multiple majors in universities, we broke free from single-disciplinary thinking and adopted valuable suggestions on "equipment miniaturization" and "process simplification", opening up new ideas for cost control.

For the public and patients, we used vivid formats such as animations and H5 to not only explain "how exosomes repair the liver" but also collect their acceptance and concerns about the new technology.

Close collaboration with clinical experts and experimental teams ensured "targeted optimization" of scientific research— from determining surface modification strategies to improve liver targeting efficiency to supplementing adaptive data for different fibrosis stages, every interaction transformed external wisdom into practical research steps.

This "co-creation" model ensures that our exosome therapy continues to move closer to the ultimate goal of "being implementable and usable" during iteration, effectively avoiding the disconnection between technology and reality.

Returning to the Value of Benefiting the Public: Taking Achievement Feedback as the "Foothold" of the Closed Loop

The ultimate value of HP work lies in promoting the "feedback of scientific research achievements to society" and effectively addressing the "accessibility" issue that patients care about most. In the "social feedback of achievements" stage, we partnered with the "Zhixing Program" (a volunteer teaching initiative) and went deep into 3 rural primary schools in Longnan, Gansu. There, we compared "exosomes" to "little couriers for the liver", used building block games to simulate the treatment process, and encouraged children to pass on the knowledge they learned to their families through "family science popularization task cards", thereby filling the cognitive gap in liver disease in rural areas.

The essence of this initiative is to drive scientific research beyond the limitations of laboratory reports, moving toward the goal of "being usable and understandable at the grassroots level", and completing the final leap from "technological breakthrough" to "social value".

From demand insight to interactive co-creation, and then to achievement feedback, our HP work has always centered on the core concept of "scientific research serving society", forming a complete closed loop. Every step stems from our belief that "technology must be rooted in society", and every action aims to make exosome therapy truly benefit those in need. We hope this HP model can provide a valuable reference for the iGEM community, and jointly promote synthetic biology to become a powerful tool for solving human health challenges.

Focusing on Reality: Scientific Questions Originating from the Real Predicaments of Liver Disease Patients

At the start of the project, we took "social demand input" as a fundamental principle. By systematically connecting patients, clinicians, and the bottlenecks of existing therapies, and proactively integrating ethical considerations, we jointly established the core R&D criterion of "safety, efficacy, and affordability". This ensures that our exosome therapy ,from its inception, is firmly anchored in the unsolved clinical problems.

"Voices Beyond Medical Records": In-Depth Patient Interviews Reveal Unmet Core Needs

To ensure our research accurately addresses patients’ most real pain points, we visited the gastroenterology wards of multiple top-tier hospitals in western China and conducted in-depth interviews with several liver fibrosis/cirrhosis patients and their families. From their tired yet sincere accounts, we touched on the triple predicaments (physical, financial, and psychological) that cannot be fully reflected in medical record data. These "voices beyond medical records" ultimately became the most critical basis for guiding our research direction.

The desire for "gentleness" and "stability": Aunt Li, a 58-year-old retired teacher, has been diagnosed with cirrhosis for 5 years. She needs to take more than a dozen medications every day, which is not only time-consuming but also accompanied by side effects such as stomach discomfort, edema, and insomnia. Liver transplantation is a cure, but the long wait for a liver source has left her tormented. "I just want a gentle treatment that allows me to spend more years with my grandchildren." Behind this sentence is a deep longing for reduced side effects and long-term disease stability.

The demand for "affordability" and "efficiency": Worker Chen, a 47-year-old construction worker, has been hospitalized repeatedly 5-6 times in two years. The severe pain of ascites and the depletion of his savings have put him under enormous pressure. "I just want treatment that is less painful, doesn’t require frequent hospitalizations, and doesn’t burden my children." His wish directly points to the pain point of existing therapies— inability to effectively control disease recurrence, leading to a surge in medical costs. His family has thus fallen into a dual dilemma of financial and energy strain, urgently needing a more affordable and effective treatment option.

The expectation for "quality of life" and "inner peace": Ms. Zhang, 34, has symptoms such as yellowing skin and pruritus caused by the disease, which seriously affect her daily life and mental state. She is even more worried that her condition will distract her children. Her family hopes for a reliable treatment that, even if it takes effect slowly, can restore stability and peace to the family.

From these real stories, we clearly summarized four major bottlenecks commonly existing in current treatment options: significant drug side effects, frequent disease recurrence, heavy financial burden, and extreme scarcity of liver sources (the ultimate treatment method). Patients’ expectations for "safety, efficacy, and affordability" have thus been transformed into specific, quantifiable research benchmarks:
In terms of safety: Must avoid the hepatotoxicity and nephrotoxicity of traditional drugs.
In terms of efficacy: Must stabilize the disease and control the progression of fibrosis.
In terms of affordability: Must strive to reduce direct treatment costs and indirect hospitalization expenses.

These real feedbacks from patients ultimately established our "patient-centered" R&D logic, driving every step of our design to address their real predicaments. (To protect patient privacy, no photos were taken during the interviews.)

"From Literature to Clinic": Evidence-Based Research and Expert Insights Define the Technical Path

On the basis of deeply understanding patient needs, we must ensure that the technical path is built on solid scientific evidence and clinical feasibility. To this end, we adopted a strategy combining "evidence-based collation" and "expert interviews". Evidence-Based Collation: Objective Evaluation of the Limitations of Existing Therapies
End-stage liver disease (ESLD) is the final stage of various liver diseases, characterized by irreversible structural damage and functional loss of liver tissue【1】. Although liver transplantation is the only potentially curative method, problems such as donor scarcity, high costs, and immune rejection severely limit its application【2】【3】. By systematically searching databases such as PubMed and CNKI, we integrated the efficacy and bottlenecks of current mainstream liver disease therapies, as shown in the table below:

Treatment Methods Main Application Stages Therapeutic Efficacy Bottlenecks/Limitations
Antiviral Therapy Liver fibrosis, early cirrhosis Effectively inhibits viral replication and slows disease progression. Cannot reverse formed fibrosis; drug resistance exists; ineffective for non-viral liver diseases.
Antifibrotic Drugs Liver fibrosis Some drugs can mildly inhibit fibrosis, but clinical efficacy is limited. Lack of specific targets; severe side effects such as hepatotoxicity and nephrotoxicity; significant individual differences in efficacy.
Lifestyle Intervention All stages Significant benefits for early-stage patients; can slow disease progression. Poor patient compliance; weak efficacy for middle-to-late stages.
Liver Transplantation End-stage liver disease The only curative method; 5-year survival rate can reach 70-80%. Severe donor shortage; high surgical risks and costs; lifelong immunosuppression required.
Interventional Therapy (TIPS) Cirrhosis complications Effectively relieves portal hypertension and improves short-term survival rate. Does not improve liver fibrosis itself; prone to complications such as hepatic encephalopathy.
Symptomatic Supportive Therapy End-stage liver disease Improves quality of life, but cannot stop the core progression of the disease. Palliative method; poor long-term efficacy; high resource consumption.

Clinical Expert Interviews: Accurately Identifying Breakthrough Points for Technology R&D
Literature collation reveals the macro-level treatment dilemmas, while the experience of frontline clinicians points out specific breakthrough directions for us. We conducted in-depth dialogues with two senior experts from the Hepatology Department of the First Clinical Medical College of Lanzhou University.

Dean Li Xun (an expert in liver fibrosis staging and diagnosis) pointed out the necessity of "precision targeting": He noted that nearly 60% of liver fibrosis patients are already at stage F2 (moderate) when diagnosed. Existing drugs have poor targeting and cannot accurately act on hepatic stellate cells (the "culprit" of fibrosis), leading to disease progression in some patients even with long-term medication. He emphasized that a therapy capable of targeted delivery would greatly improve efficacy and reduce systemic side effects— this directly inspired our idea of using exosomes as "precision navigation" carriers.

Fig1-Dr. Li Xun is performing a liver transplant surgery

Associate Director Yan Jun (an expert in perioperative management of liver transplantation) proposed the urgent need for "bridging therapy": In his department, more than 80 patients wait for liver transplantation every year, but only about 20 liver donors are available. During the waiting period of several months, approximately 30% of patients’ conditions deteriorate to the point where they lose eligibility for transplantation. He suggested that if exosome therapy could be used as a "pre-transplant bridging" program to help patients stabilize liver function and survive the waiting period, it would have enormous clinical value. In addition, he recommended using exosomes to deliver targeted miRNAs to intervene in complications, achieving a more fundamental treatment effect.

Fig2-Dr. Li Xun

Integrating the urgent needs of patients, the bottlenecks of existing therapies, and the core suggestions of clinical experts, our research direction became clear: To develop a new therapy that can not only accurately resist fibrosis but also has the potential to be used as pre-transplant bridging therapy, using engineered exosomes as carriers and loading specific targeted miRNAs to target hepatic stellate cells.

"Ethics First": Building an Ethical and Compliant Framework for Responsible Innovation Path

An innovation aimed at helping patients must place ethical care and regulatory compliance at its core from the very beginning. We systematically identified ethical key points and formulated practical paths around the entire process of exosome therapy:

In terms of donor source management: Ensure informed consent and compliance with genetic resource regulations. The sources of exosomes (such as umbilical cords and adipose mesenchymal stem cells) involve human genetic resources, which are strictly regulated by the Regulations on the Management of Human Genetic Resources. To this end, we formulated strict operating guidelines: When using umbilical cord sources, we designed a dedicated informed consent form to clearly distinguish between "scientific research donation" and "commercial self-storage", and explained the core clauses in plain language to ensure that parturients make voluntary choices based on full understanding.

In terms of research process ethics: Strictly control risks and ensure quality. We clearly stated that exosome therapy is still in the clinical research stage and must comply with the Administrative Measures for Stem Cell Clinical Research— it must be carried out in registered hospitals and no fees shall be charged to subjects. We focused on two aspects: First, risk-benefit ratio assessment— truthfully informing patients of potential risks and the uncertainty of benefits; second, standardized quality control— establishing strict preparation and testing processes to address "batch-to-batch variation" and respond to patients’ expectations for "stable, non-recurrent" treatment.

In terms of clinical application ethics: Guard against commercial chaos and ensure information transparency. In response to illegal treatments and false promotions existing in the current market, we emphasized the need to collaborate with regulatory authorities to protect patient rights and interests. When communicating with patients, we clearly distinguished between "clinical research" and "mature treatment", and objectively explained the advantages and limitations of the program. At the same time, we established a long-term follow-up mechanism to promptly feedback changes in the patient’s condition, alleviating the anxiety caused by information asymmetry.

The ultimate goal of ethical practice is to respond to patients’ simple wish of "receiving treatment with peace of mind". Only by integrating rigorous regulatory requirements with profound humanistic care can technological innovation truly become a healing force that warms people’s hearts.

Co-Creating the "Messenger": Iterating Exosome Therapy Programs with Diverse Wisdom

After completing the initial demand input, "social interactive co-creation" became a key link for us to break the cognitive barriers of the research team and ensure the program does not deviate from real needs. We designed a diversified interaction mechanism, inviting university teachers and students, clinical experts, patients, and the public to participate together, integrating their wisdom and experience into project iteration. Every interaction became a catalyst for feeding back into scientific research, transforming external feedback directly into motivation for program optimization, and driving our exosome therapy research to move forward continuously toward the goal of "being implementable and truly useful".

"Campus Think Tank":Optimizing Program Practicality from an Interdisciplinary Perspective

To test and improve the feasibility and convenience of the program in a laboratory environment, we held a special lecture on "New Paths for Liver Disease Treatment" for undergraduates with multi-disciplinary backgrounds from top Chinese universities. Through group discussions and questionnaire feedback, we gained valuable suggestions from different disciplinary perspectives. Although these suggestions did not involve core technological breakthroughs, they accurately optimized the "practicality" gene of the project.

The bioscience major focused on optimizing experimental efficiency. Students questioned the efficiency of the exosome extraction process, pointing out that ultracentrifugation is time-consuming (6-8 hours) and has poor purity (impurity protein removal rate <85%). This feedback prompted the experimental team to take immediate action: by adjusting centrifugation parameters (e.g., increasing the speed from 10,000g to 12,000g) and optimizing the process, they successfully reduced the time for a single extraction to within 5 hours and increased the impurity protein removal rate to 90%, effectively solving the sample preparation bottleneck in the early stage of the project.

Fig3-Discussion among students from different majors

The medical major focused on enhancing targeting accuracy. Students majoring in clinical medicine proposed from the perspective of pathophysiology that exosomes without precise targeting may cause off-target effects on normal hepatocytes. They suggested that "cell-specific peptides" could be used for surface modification to improve targeting. This suggestion aligned with our plan and promoted us to launch a pre-experiment in advance. The results showed that the enrichment rate of exosomes modified with C1q short peptides in hepatic stellate cells increased by approximately 30%, laying a solid foundation for subsequent engineering modification.

Fig4-Discussion among students from different majors

The engineering major focused on improving equipment adaptability. Students majoring in materials and mechanical engineering pointed out that the existing large centrifuges (covering an area of 1.2㎡) have problems of inconvenient movement and complex operation from the perspective of space utilization and operational convenience. Based on their suggestions, we researched and replaced it with a mini ultracentrifuge, which not only reduced the floor area to 0.5㎡ but also shortened the training time for new team members from 2 days to half a day, significantly improving the flexibility and convenience of the experiment.

The humanities and social sciences major focused on promoting the popularization of publicity. Students majoring in Chinese language and administrative management suggested that safety data should be presented in more intuitive charts, and professional terms should be replaced with popular metaphors such as "liver-exclusive navigation" to facilitate public understanding. Based on this, we produced the Exosome Therapy Safety Verification Summary Table and optimized the popular science language— this not only improved the transparency of the project but also accumulated valuable materials for subsequent social feedback activities.

"Clinical and Social Consensus":Driving Three Strategic Iterations of Core Technology

Interactions with students optimized the "operability" of the project, while in-depth collaboration with clinical experts and patient communities directly reshaped the core strategy of our treatment program. Based on real clinical feedback and social concerns, we completed three key technological iterations. Iteration 1: From "Single-Target Attack" to "Network Regulation" — Solving the Clinical Drug Resistance Bottleneck
Our initial idea, based on clear laboratory data, was to use a single miRNA (miR-455-3p) to inhibit the Notch single signaling pathway.

However, frontline liver disease experts pointed out sharply that this "single-target" strategy is highly likely to fail in complex clinical settings. One chief physician shared a typical case: The patient improved initially after using a single-pathway inhibitor, but relapsed three months later due to the "compensatory activation" of the HSF1 pathway. The real clinical need is a "combination strategy" that can suppress multiple key pathways simultaneously.

Combined with mechanism verification by scientific research experts, we confirmed the "crosstalk" relationship between the Notch and HSF1 pathways, and introduced miR-148a-5p which can inhibit the HSF1 pathway. Finally, we constructed a dual-miRNA network with the synergistic effect of miR-455-3p and miR-148a-5p [4][5][6]. This strategic upgrade aims to fundamentally block "pathway compensation" through multi-pathway synergistic regulation, improve the durability of treatment, and simultaneously achieve the dual effects of "anti-fibrosis" and "anti-inflammation", systematically addressing clinical pain points.

Fig5-Experimental plan discussion - HP group, experimental group and clinical doctors

Iteration 2: From "Basic Homing" to "Precision Guidance" — Responding to Doctor-Patient Safety Concerns
We once planned to rely on the natural liver homing effect of MSC exosomes for "basic delivery".

A doctor from the interventional therapy department raised a sharp safety question: "How to ensure that the drug acts accurately on diseased cells rather than damaging normal hepatocytes?" At the same time, through surveys of patient communities, we found that patients generally feel fear and anxiety about the side effects of existing therapies that "harm one thousand enemies and damage eight hundred".

The professional questions of doctors and the safety demands of patients jointly pushed "precision delivery" to the core position. We collaborated with the School of Materials Science to screen and identify peptides with specific binding capabilities to hepatic stellate cells, and used them for the engineering modification of exosome surfaces. Experiments proved that exosomes after engineering modification are like being equipped with a "precision guidance system" — their targeting efficiency is significantly improved, and the non-specific adsorption to normal hepatocytes is greatly reduced. This optimization is a strong response to doctors’ technical questions and a solemn commitment to patients’ safety demands.

Fig6-Experimental plan discussion - HP group and experimental group

Iteration 3: From "Efficacy First" to "Experience-Oriented" — Balancing Treatment Accessibility and Humanization
In the early stage of the project, our focus was mainly on improving treatment efficacy.

During continuous interactions with patients and their families, we deeply realized that the convenience and accessibility of treatment directly determine the quality of life and dignity of patients. Frequent drug administration and high costs are another heavy burden for them besides the disease itself.

This insight prompted us to integrate "humanized design" into R&D. We fully utilized the natural long-acting circulation characteristics of exosomes, and strived to reduce the frequency of drug administration and alleviate the burden on patients by optimizing the administration plan and preparation process. At the same time, in the selection of technical paths, we prioritized solutions with large-scale production potential, such as genetic engineering modification, to lay the groundwork for future "treatment accessibility".

Through this series of iterations driven by social interaction, our project has transformed from a basic laboratory concept into a comprehensive treatment program with clinical feasibility, safety, and humanistic care. This process has built a positive interaction model of "scientific research - clinic - society" and deepened our understanding of the iGEM spirit of "cooperation and co-creation".

Sowing Hope-Bringing Awareness of Cutting-Edge Therapy to Rural Classrooms

After completing the preliminary exploration of exosome therapy, we did not let the achievements stop at the laboratory. In response to the pain point of "significant cognitive gaps in liver disease in rural areas" identified in previous surveys, we chose to turn our attention to the corners most in need of popular science and launched our journey of social feedback.

Origin and Design:How to Communicate with Rural Children?

Surveys showed that some villagers regard liver fibrosis as an "incurable disease" or have fears about new therapies. To break this cognitive barrier, we partnered with the "Zhixing Program" volunteer teaching team and entered 3 rural primary schools in the mountainous area of Longnan, Gansu. We hoped to spread the seeds of health into every family through children. To make complex scientific knowledge understandable and acceptable to children, we carried out a thorough creative transformation of the popular science content from a "child’s perspective":

We compared "exosomes" to "little couriers for the liver" and described "targeted miRNAs" as the "drug packages" they carry. The process of liver fibrosis was designed as a "defense battle of the liver castle", and exosome therapy was the "support force" coming to the rescue.

In addition, we produced hand-drawn comics and "cell model building blocks". Children could personally build "healthy" and "fibrotic" livers, and move the "blue building blocks" representing exosomes to intuitively simulate the process of "repairing damaged cells". This "visualization + interaction" design turned boring knowledge into an interesting game.

Fig7-A painting created by children in volunteer teaching based on liver disease

Fig8- Volunteers introduce exosome therapy for liver cirrhosis to children

Responses and Insights:The Ripple Effect of Knowledge

The positive feedback from children in the classroom exceeded our expectations. A sixth-grade boy, after seeing the comic, held up a building block and asked curiously: "Will this 'little courier' get lost?" This question provided us with an excellent opportunity to explain the principle of "targeted modification". What moved us even more was that when talking about healthy living habits, a fourth-grade girl immediately said: "I will go back and tell my grandma not to drink water that has been left for several days!"

At this moment, we deeply realized that children are not only receivers of knowledge but also "little links" connecting scientific research and families, and breaking the intergenerational information barrier. Rural parents often ignore liver disease prevention due to busy lives or limited information channels, while the innocent and straightforward "childlike science popularization" of children can most effectively root health awareness in daily family life.

To amplify this effect, we designed "family science popularization task cards". Nearly 80% of the children carefully recorded their interactions with their families in the collected cards. One child wrote: "Dad said he will no longer drink too much alcohol in the future, for fear of liver disease"; a parent left a message on the back of the card: "It’s the first time I’ve heard of such a gentle liver disease treatment method, and I hope it can be truly used in the future." These feedbacks confirmed that our initiative successfully delivered scientific knowledge and health concepts to the groups that need them most through the family communication chain.

Future Outlook:From " One-Time Outreach " to " Sustained Symbiosis "

Although this volunteer teaching achieved initial success, a one-time activity is far from the end. From the perspective of continuously optimizing HP, we clearly recognize the existing shortcomings and have planned future directions based on this.

First, filling the "sustainability gap": Knowledge is easily forgotten after a one-time popular science class. To this end, we plan to establish long-term cooperation with local schools, produce a series of popular science short animations, and train local teachers to become "popular science liaisons", integrating health education into daily life and realizing the transformation from "short-term volunteer teaching" to "long-term companionship".

Second, improving "personalized adaptation": A unified curriculum cannot meet the cognitive needs of children of different age groups. In the future, we will develop interactive picture books for lower grades and design mini-scientific experiments for higher grades to achieve hierarchical and precise popular science.

Third, opening up the "reverse feedback loop": We found that parents’ concerns about treatment costs and cycles are precisely important directions for guiding the optimization of our scientific research, but this information chain has not yet been connected. In the future, we will add "family demand questionnaires" to popular science activities to systematically collect real demands at the grassroots level and directly feed them back to the experimental team to guide the optimization of programs such as low-cost preparation and long-acting drug administration, truly realizing the two-way cycle of "social interaction ⇌ scientific research optimization".

The "achievement feedback" of HP is not a one-way "giving", but a "symbiotic" relationship: We pass on knowledge to children, children pass on awareness to families, and families ultimately pass on valuable demands that drive scientific research to be closer to reality to us. We will carry these reflections, make popular science more warm and effective, and make exosome therapy not only a laboratory breakthrough but also a hope that people in remote areas can "understand, look forward to, and access".

Overall Reflection: From Exosome Technology Innovation to a Universal Social Solution

Looking back on the HP journey of this project, we have never regarded it as an "additional question" for scientific research, but always as a core driving force throughout the project from conception to implementation. The closed loop of "demand input → interactive co-creation → achievement feedback" we built closely connects laboratory exploration with the broad social reality. From the heartfelt voices of patients in the wards of the First Clinical Medical College of Lanzhou University to the "liver castles" built by children on the desks of rural primary schools in Longnan, Gansu, every interaction has profoundly shaped the direction of the project, allowing our scientific research path to take root in the soil of real society.

At the beginning of the project, we entered the clinic with the question of "how to implement technology", and the personal experiences of patients calibrated our direction. The vivid predicaments quickly made us jump out of the mindset of simply pursuing technical parameters such as "extraction efficiency", and instead placed humanistic goals such as "avoiding hepatotoxicity and nephrotoxicity" and "reducing the number of hospitalizations" at the top. Patients’ simple expectations for "safety, efficacy, and affordability" became an important driving force for our R&D. At the same time, through the evidence-based collation of existing therapies, we found that macro data such as "severe shortage of liver sources" and "significant drug side effects" resonated with patients’ individual sufferings— this allowed us to accurately anchor our research focus on the real need of "targeting hepatic stellate cells and blocking fibrosis" from the very beginning. To break the cognitive limitations within the team, we also proactively embraced society, allowing diverse wisdom to become a key force in reshaping the program.

At the laboratory operation level, students from different professional backgrounds brought us a "practical revolution":

The questioning of ultracentrifugation efficiency by bioscience students directly prompted us to reduce the extraction time from 8 hours to 5 hours and increase the purity to 90%.

The targeting suggestions of clinical medicine students promoted the launch of key pre-experiments, increasing the exosome enrichment rate by 30%.

The suggestions on equipment adaptability from engineering students not only saved us valuable laboratory space but also improved the work efficiency of the team.

At the core technology strategy level, in-depth dialogues with clinical experts led to a complete "restructuring": Our initial idealized design of "focusing on a single pathway" was decisively revised in the face of experts’ clinical experience that "pathway compensation easily leads to recurrence". Finally, we constructed a dual-pathway synergistic regulation program of "anti-fibrosis + anti-inflammation", and further clarified the clinical positioning of the product based on the urgent need for "pre-transplant bridging therapy". At the same time, in response to the common safety concerns of doctors and patients, we completed the surface engineering modification of exosomes, realizing the leap from "basic delivery" to "precision guidance".

Throughout the process, ethical considerations have always gone hand in hand with scientific research. The dedicated informed consent forms we designed and the personalized explanations provided to donors from different cultural backgrounds aim to ensure that informed consent is not a mere formality. In risk assessment, we transformed Aunt Li’s wish to "accompany her grandchildren" and Worker Chen’s concern about his ability to work into quantitative indicators for evaluating "patients’ quality of life". The popular science manuals we produced are designed to help patient families resist the harm of false medical information. Behind these actions is our firm belief: Ethics is not a cold compliance checklist, but the integration of patients’ most fundamental wish of "receiving treatment with peace of mind" into every detail of scientific research.

In the final stage of the project, we chose to go deep into rural areas and sow the seeds of science in the places that need them most. Through the story of "little couriers for the liver" and "family science popularization task cards", we were delighted to see health awareness spread between children and parents. But more importantly, we conducted in-depth reflections during this process: A one-time volunteer teaching cannot bring sustained changes, and standardized courses also need personalized adjustments. We realized that we must open up the reverse loop from "grassroots needs" to "scientific research optimization". In the future, by adding "family demand questionnaires" and other methods, we will allow the real demands of rural areas to become a guide for subsequent research on low-cost preparation and long-acting drug administration, realizing the two-way engagement between scientific research and society.

Looking back on the entire process, our greatest gain is truly understanding the connotation of iGEM’s "scientific research serves society"— it is not a slogan, but every listening session in the ward, every suggestion accepted from different professions, and every moment of squatting down to build blocks with children. In the future, we will continue to improve this HP model, allowing exosome therapy technology to truly take root in real needs. We hope that this practice, which originated from society, was co-created with society, and ultimately gave back to society, can provide a reference for the iGEM community: to make cutting-edge technology no longer out of reach, but a solution that can warm everyone in need.

Reference

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[2] Kostallari, E., Valainathan, S., Biquard, L., Shah, V. H., & Rautou, P. E. (2021). Role of extracellular vesicles in liver diseases and their therapeutic potential. Advanced drug delivery reviews, 175, 113816.

[3] Li, L., Liu, Y., Wang, K., Mo, J., Weng, Z., Jiang, H., & Jin, C. (2025). Stem cell exosomes: new hope and future potential for relieving liver fibrosis. Clinical and molecular hepatology, 31(2), 333–349.

[4] Li, L., Liu, Y., Wang, K., Mo, J., Weng, Z., Jiang, H., & Jin, C. (2025). Stem cell exosomes: new hope and future potential for relieving liver fibrosis. Clinical and molecular hepatology, 31(2), 333–349.

[5] Zhou Q, Rong C, Gu T, Li H, Wu L, Zhuansun X, Zhao X, Xiao Z, Kuang Y, Xu S, Wang S. Mesenchymal stem cells improve liver fibrosis and protect hepatocytes by promoting microRNA-148a-5p-mediated inhibition of Notch signaling pathway. Stem Cell Res Ther. 2022 Jul 26;13(1):354.

[6] Yuan M, Yao L, Chen P, Wang Z, Liu P, Xiong Z, Hu X, Li L, Jiang Y. Human umbilical cord mesenchymal stem cells inhibit liver fibrosis via the microRNA-148a-5p/SLIT3 axis. Int Immunopharmacol. 2023 Dec;125(Pt A):111134.

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