Guide:

Recently, Beijing Daxiang Technology Co., Ltd., together with researchers from Peking University People's Hospital, Peking University and Merck Innovation Center, jointly published an organ-like culture system based on nested microarray organ chips (Organ-like chip). Compared with the traditional plate culture platform, the organo-like chip not only promotes the growth of organ-like organs, but also improves the stability of the culture system, providing a rapid and repeatable new drug screening platform for the precise treatment of tumor.

Precise medical treatment for cancer refers to finding the most effective and safe treatment method for the patient by predicting the response of the patient to different drugs. Currently, high throughput sequencing technology (NGS) is used The detection of tumor mutation genes and the use of targeted drug therapy are regarded as the conventional means of tumor precision medicine. However, the biological behavior of different tumors is quite different, and not all tumors have clear driving genes. Therefore, the proportion of mutations of targeted genes detected in different types of tumor samples is different. Some studies show that only a small number of patients can benefit from NGS, and the treatment status of most patients has not been effectively improved

Another means to achieve accurate cancer treatment is different from the process of NGS pushing "results" from "causes", but directly based on "results" (phenotypes), to intuitively detect the killing results of different drugs on patients' tumors, so as to find the best drug regimen. The patient-derived xenotransplantation model (PDX) has been used in this way, but the limitations of PDX such as long time, low success rate of model construction and high cost greatly limit its clinical application

As an innovative and highly bionic model, patient-derived organoid (PDO) is more and more popular in clinical applications because it can well preserve the cellular structure and molecular characteristics of tumor tissue, and its drug sensitivity detection has high accuracy in predicting the efficacy of patients, and has many advantages such as short operating cycle in vitro. In June 2022, theExpert Consensus on the Guidance of Organ-like Drug Sensitivity Test on the Clinical Application of Tumor Precision Therapy (2022 Version)jointly prepared by several clinical experts was officially released, which also fully confirmed the potential of PDO in tumor precision medicine

Although PDO has made remarkable progress in clinical treatment, the current traditional PDO culture method based on orifice plate has many disadvantages, such as slow growth rate, poor organoid homogeneity, and low repeatability of efficacy results, There are great limitations in practical application. Therefore, the industry is also constantly exploring and iterating new PDO training system to improve its timeliness and stability

Recently, Beijing Daxiang Technology Co., Ltd., together with researchers from Peking University People's Hospital, Peking University and Merck Innovation Center, jointly published aOrgan-like culture system based on nested microarray organ chip (organo-like chip). Compared with the traditional orifice plate culture platform, the organoid chip not only promotes the growth of organoid, but also improves the stability of the culture system, providing a rapid and repeatable new drug screening platform for precise tumor treatment

The figure shows the cross-sectional structure of a cell of the chip. A mixture of 50% matrigel and organoid can be added into the micropores nested at the bottom of the chip, so as to carry out 3D culture of organoid; The drug to be tested can be added to the upper reservoir (a); At the same time, the differences in growth kinetics of organoids on different culture platforms were also shown (b). The special structural design of the chip ensures that the organoid can grow in a centralized and controlled manner

Organ-like chips promote the growth efficiency and stability of organ-like cells & nbsp;

The researchers first constructed mouse small intestine and colon organoids (a) on the organoid chip, and compared the budding rate (b) and growth area (c) of intestinal organoids under different culture systems, As well as the growth curve (d) of organoid under different inoculation densities (per microliter of cells), it can be found that the growth rate of organoid has been significantly improved under the organoid chip culture system

At the same time, the CV value difference (e) and organ-like size (f) of organ-like ATP in different culture platforms were compared. It can be seen that the organ-like chip significantly improved the stability of organ-like culture. These results show that the organoid chip can provide a precise controlled microenvironment for organoid culture. On the one hand, it can improve the speed of organoid culture, reduce the service cycle of organoid precision medicine, and find effective treatment methods for patients more quickly in the valuable treatment window period of patients; On the other hand, it improves the stability of the results and makes the efficacy results more accurate

High clinical consistency of organoid chip & nbsp;

The researchers constructed a patient-derived colorectal cancer-like organ on the organoid chip, and found that the diameter of the organoid reached 100 microns at the 7th day of cultivation, which can meet the needs of drug screening (a). At the same time, the researchers also carried out corresponding biological characterization of PDO and primary tumor tissue of patients: based on pathological detection, organoid microarray was highly consistent with the original sample in terms of tissue morphology and tumor specific marker expression (b); Through full exon analysis, the organ-like chip well preserved the gene copy number (c), point mutation feature (d) and cancer-driven gene (e) of the original sample. High clinical consistency ensures that the pharmacodynamic results of organoid chips can reflect the actual drug use of patients and improve the clinical benefits of patients

Organ-like chip platform for precise tumor treatment & nbsp;

Finally, the researchers established PDO models of 3 patients on organoid cores and selected 9 clinically common colorectal cancer treatment methods for drug sensitivity screening (a-i). It can be found that different patients have great differences in drug tolerance, which also confirms the heterogeneity among tumor patients (j). It is particularly important that the pharmacodynamic results of organoid chips have very high stability, the average CV is less than 10% (k), and the Z factor is about 0.75 (l). Therefore, organoid chips provide a repeatable platform for drug screening, and also reproduce the heterogeneous response of individual patients to anticancer drugs

At the same time, compared with the actual clinical medication of three patients, the drugs screened by the PDO model based on the organoid chip have achieved good therapeutic effect in the actual clinical practice

About Big Oak & nbsp;

Beijing Daxiang Technology Co., Ltd., founded in 2018 and headquartered in Beijing, is China's leading high-tech company in the research and development and production of human organoid chips, committed to promoting and leading the wide application of organoid chips in new drug research and development, disease modeling, personalized precision medicine and other fields. The company expects to provide more accurate, more efficient and more economical drug R&D solutions and innovative and biomimetic standardized platform for clinical precise drug use, so as to promote the development of human health