Moment of Transition Tissues Produced from Stem Cells and Microphysiological Systems: A Framework

Charlotte Lewis^*
*Correspondence: Charlotte Lewis, Departments of Pathology, Cell Biology, University of Perth, Australia, Email:

Description

Almost all cancer-related deaths are caused by metastasis. The protective milieu of the metastatic niche limits the efficiency of cancer therapies, and as a result, these disseminated cancers remain incurable. Because of a dearth of relevant model systems, metastatic disease progression remains poorly understood. To close this knowledge gap, we propose an all-human micro physiological system for studying cancer behaviour in the liver metastatic habitat. This current Liver Chip is a 3D-system that models the hepatic niche. It contains a full complement of human parenchymal and non-parenchymal cells and effectively mimics micrometastases. Furthermore, this approach enables real-time monitoring of micrometastasis as well as assessment of humanspecific signals [1].

It is being used to advance our understanding of chemotherapeutic efficacy by investigating the activity of existing and novel drugs on micrometastases under circumstances that replicate diurnal fluctuations in hormones, nutrition, and mild inflammatory states utilising programmable microdispensers. These cues have an effect on the cues that drive tumour cell responses. The following signalling groups are being studied glucose/insulin responses, the stress hormone cortisol, and the gut microbiome in response to inflammatory signals. Currently, the system can sustain functioning hepatocytes for at least 15 days, as measured by urea, antitrypsin, fibrinogen, cytochrome P450, and damage. Breast cancer cell lines readily integrate into the hepatic niche without causing observable tissue disturbance, and preliminary evidence suggests that a subgroup of breast cancer cells experiences growth inhibition. Map technology, in conjunction with systems biology modelling, is also used to assess cellular crosstalk and depict communication networks in the early microenvironment of micrometastases. This model is expected to identify new therapeutic options for metastasis by clarifying the paracrine effects of hepatic and metastatic cells while also evaluating drug efficacy for metastasis [2].

Metastasis is the leading cause of cancer-related death. Metastases are caused by a set of consecutive biological processes that allow cancer cells to move from a primary site to secondary organs. Intravasation into the circulation followed by extravasation into the parenchyma of a distant organ allows cells to escape from the underlying tumour. Those cells that successfully disperse may either grow immediately or stay latent for years to decades as tiny or pre-malignant micrometastases before becoming clinically obvious. This is especially concerning in the case of breast cancer, where, while the primary tumour is frequently effectively treated, up to 30% of women with early stage breast cancer will subsequently recur with metastatic illness. Because of the broad development of metastatic tumours. The limits of current model systems are one of the biggest impediments to the development of cancer treatments that target micrometastases [3,4]. Animal models are not appropriate for this type of research because they often only give endpoint assessments in addition to issues relevant to the human situation.

Although immunocompromised mouse models are commonly employed, investigations have shown that immune systems are important in the micrometastatic microenvironment. Because of interspecies variances in cytokines and metabolism, animal researches that use syngeneic models are not fully representative of the human condition. During in vitro culture research current 2D culture systems lack essential characteristics that effect tumour behaviour, such as 3D design to give tissue depth for tumour intercalation; functional aspects, such as fluid flow and oxygen content regulation, and do not allow for extended culture. There is also a notable lack of models capable of reproducing micrometastasis while also evaluating drug efficacy, toxicity, and metabolism. To address these difficulties, a number of researchers have used organotypic cultures in bioreactors as investigative tools.

The liver is an appropriate organ system for studying micrometastasis as well as the efficiency of cancer therapies. For starters, it is a prominent location of metastasis for a variety of carcinomas, including breast, lung, colon, prostate, brain, and melanomas. Hepatic metastases affect 30–70% of cancer patients, depending on the underlying tumour type. Second, the liver is the primary location for drug metabolism, both activation and detoxification, which is important in evaluating efficacy and reducing toxicities in cancer therapy. Furthermore, there is evidence that metastatic disease affects liver function, potentially increasing toxicity and modifying the agent's potency against the tumour [5].

Conflict of Interest

None.

References

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