Conditionally Reprogrammed Cells and Robotic High-Throughput Screening for Precision Cancer Therapy

Alkhilaiwi, Faris

doi:10.3389/fonc.2021.761986

Cited by 4 publications

(3 citation statements)

References 90 publications

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“…In order to enhance the success rate of primary cancer cell culture, the utilization of conditional reprogramming has been explored. By employing a co-culture approach involving fibroblast cells and the supplementation of Y-27632, the success rate has been significantly improved [41]. Further optimization of the conditional reprogramming technique holds the potential to further enhance the success rate of LCO cell culture.…”

Section: Discussionmentioning

confidence: 99%

Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids

Park

Lee

Kim

et al. 2023

Cells

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One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent need to successfully generate LCOs from biopsy specimens. Conventional lung biopsy techniques, such as transthoracic needle biopsy and forceps biopsy, only yield small amounts of lung tissue, resulting in a low success rate for culturing LCOs from biopsy samples. Furthermore, potential complications, like bleeding and pneumothorax, make it difficult to obtain sufficient tissue. Another critical issue is the overgrowth of normal lung cells in later passages of LCO culture, and the optimal culture conditions for LCOs are yet to be determined. To address these limitations, we attempted to create LCOs from cryobiopsy specimens obtained from patients with lung cancer (n = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (n = 46). Transbronchial cryobiopsy enables the retrieval of significantly larger amounts of lung tissue than bronchoscopic forceps biopsy. Additionally, cryobiopsy can be employed for peripheral lesions, and it is aided via radial endobronchial ultrasonography. This study significantly improved the success rate of LCO culture and demonstrated that the LCOs retained characteristics that resembled the primary tumors. Single-cell RNA sequencing confirmed high cancer cell purity in early passages of LCOs derived from patients with advanced lung cancer. Furthermore, the three-dimensional structure and intracellular components of LCOs were characterized using three-dimensional holotomography. Finally, drug screening was performed using a specialized micropillar culture system with cryobiopsy-derived LCOs. LCOs derived from cryobiopsy specimens offer a promising solution to the critical limitations of conventional LCOs. Cryobiopsy can be applied to patients with lung cancer at all stages, including those with peripheral lesions, and can provide sufficient cells for LCO generation. Therefore, we anticipate that cryobiopsy will serve as a breakthrough strategy for the clinical application of LCOs in all stages of lung cancer.

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Section: Discussionmentioning

confidence: 99%

Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids

Park

Lee

Kim

et al. 2023

Cells

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“…In addition to the intrinsic limitations of cancer cell lines, most traditional cell lines used today are without detailed documentation for treatment. The cell lines are over-simplified for different therapies, which may lead to overtreatment, inefficiency, and even unnecessary side effects [ 29 , 30 ]. The radioresistant and radiosensitive CR cell lines established in the current study maintained the characteristics of the original PDTs both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Insights into the characteristics of primary radioresistant cervical cancer using single-cell transcriptomics

Xing

Chen

et al. 2023

Human Cell

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Radioresistance is a major cause of radiotherapy failure among patients with cervical cancer (CC), the fourth most common cause of cancer mortality in women worldwide. Traditional CC cell lines lose intra-tumoral heterogeneity, posing a challenge for radioresistance research. Meanwhile, conditional reprogramming (CR) maintains intra-tumoral heterogeneity and complexity, as well as the genomic and clinical characteristics of original cells and tissues. Three radioresistant and two radiosensitive primary CC cell lines were developed under CR conditions from patient specimens, and their characteristics were verified via immunofluorescence, growth kinetics, clone forming assay, xenografting, and immunohistochemistry. The CR cell lines had homogenous characteristics with original tumor tissues and maintained radiosensitivity in vitro and in vivo, while also maintaining intra-tumoral heterogeneity according to single-cell RNA sequencing analysis. Upon further investigation, 20.83% of cells in radioresistant CR cell lines aggregated in the G2/M cell cycle phase, which is sensitive to radiation, compared to 38.1% of cells in radiosensitive CR cell lines. This study established three radioresistant and two radiosensitive CC cell lines through CR, which will benefit further research investigating radiosensitivity in CC. Our present study may provide an ideal model for research on development of radioresistance and potential therapeutic targets in CC.

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“…More than 80% of men with PCa have metastatic disease in bones and it is a known challenge to obtain adequate bone tissue samples for genetic sequencing. Moreover, proteomics, organoid cultures, and patient-derived xenograft-model may not always reveal the pathophysiology of a disease [ 94 , 95 , 96 ]. Prior to the invention of the CR technique, it was challenging to develop efficient and straightforward procedures in a single model with a high success rate.…”

Section: Applications Of Cr Cells In Pca Initiation and Progressionmentioning

confidence: 99%

Patient-Derived Conditionally Reprogrammed Cells in Prostate Cancer Research

Elbialy,

Kappala,

Desai

et al. 2024

Cells

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Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research. This review explores the applications of the conditional reprogramming (CR) cell culture approach, showcasing its capability to rapidly and effectively cultivate patient-derived normal and tumor cells. The CR strategy facilitates the acquisition of stem cell properties by primary cells, precisely recapitulating the human pathophysiology of PCa. This nuanced understanding enables the identification of novel therapeutics. Specifically, our discussion encompasses the utility of CR cells in elucidating PCa initiation and progression, unraveling the molecular pathogenesis of metastatic PCa, addressing health disparities, and advancing personalized medicine. Coupled with the tumor organoid approach and patient-derived xenografts (PDXs), CR cells present a promising avenue for comprehending cancer biology, exploring new treatment modalities, and advancing precision medicine in the context of PCa. These approaches have been used for two NCI initiatives (PDMR: patient-derived model repositories; HCMI: human cancer models initiatives).

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Conditionally Reprogrammed Cells and Robotic High-Throughput Screening for Precision Cancer Therapy

Cited by 4 publications

References 90 publications

Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids

Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids

Insights into the characteristics of primary radioresistant cervical cancer using single-cell transcriptomics

Patient-Derived Conditionally Reprogrammed Cells in Prostate Cancer Research

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