Microfluidic model for B-cell lymphoma
(2020) KIMM05 20201Department of Immunotechnology
- Abstract
- Cancer patients often show varying response when given the same treatment for the same cancer type. This is especially true for cancer types with high molecular heterogeneity such as B-cell lymphomas which is a haematological cancer subtype. Because of this varying treatment response, research is moving towards enabling personalized medicine where a treatment is selected for each individual patient. To enable personalized treatment in clinics many steps need to be made. In vitro models that mimic the in vivo environment can be used to culture primary patient samples. Using a previously published in vitro model for B cell lymphoma, published by Mannino et al (2018), this thesis project is aimed at creating a microfluidicsbased culture... (More)
- Cancer patients often show varying response when given the same treatment for the same cancer type. This is especially true for cancer types with high molecular heterogeneity such as B-cell lymphomas which is a haematological cancer subtype. Because of this varying treatment response, research is moving towards enabling personalized medicine where a treatment is selected for each individual patient. To enable personalized treatment in clinics many steps need to be made. In vitro models that mimic the in vivo environment can be used to culture primary patient samples. Using a previously published in vitro model for B cell lymphoma, published by Mannino et al (2018), this thesis project is aimed at creating a microfluidicsbased culture system that can potentially mimic the extracellular environment within lymph nodes. The objective is to develop a model for mantle cell lymphoma (MCL) which is a particularly aggressive B-cell lymphoma subtype and which has high diversity of response to currently available therapies. Our results show that it is possible to grow B- and T-cells in our constructed microfluidic setups and that the growth is of the same magnitude when compared to static cultures. This opens the possibility of creating a model that can be used in clinics to determine specific treatment methodology for mantle cell lymphoma patients. (Less)
- Popular Abstract
- Cancer is one of the most common causes of death in the world. There are multiple cancer types which all behave differently based on their biology. Until recently, treatment has been limited to chemotherapy and surgical interventions. But because of the molecular variation in cancer and among health status of patients the treatment response is varying. This diversity in responses to treatment has opened the door to personalized treatment, where a patient would be given a more tailored treatment.
One group of cancers are the lymphomas that derive from the immune system and where there is a large diversity between patient in relation to drug resistance. Thus, personalized medicine could be an important step toward improved treatment,... (More) - Cancer is one of the most common causes of death in the world. There are multiple cancer types which all behave differently based on their biology. Until recently, treatment has been limited to chemotherapy and surgical interventions. But because of the molecular variation in cancer and among health status of patients the treatment response is varying. This diversity in responses to treatment has opened the door to personalized treatment, where a patient would be given a more tailored treatment.
One group of cancers are the lymphomas that derive from the immune system and where there is a large diversity between patient in relation to drug resistance. Thus, personalized medicine could be an important step toward improved treatment, especially in aggressive lymphoma subtypes such as Mantle cell lymphoma (MCL).
For personalisation, not only do we need better treatment drugs but also a way to evaluate them with respect to how each patient will respond. This would help in creating patient specific treatment regimens. Thus, a possible way is to test the effect of drugs on the patient‘s own tumor cells derived from biopsy samples, as their behaviour can be extrapolated to patient response to treatment and thus outcome. Hence, culturing these cells in lab is important. These growth models are usually referenced to as in vitro models. This thesis aimed to create such a model for culturing MCL patient cells using simple tools readily available in most labs. For this purpose, we utilised the concept of microfluidics i.e. manipulation of fluid at micro scales, to create microchips and thus establish a dynamic setup.
These microchips were made of silicone (PDMS). The moulds had a culture chamber in the centre and two channels, one inlet and one outlet leading to it. The chamber was filled with hydrogel containing either B- or T-cells from lymphoma-specific cell lines. These cells are two types of immune cells vital to our system. The inlet was connected to tubing system with syringes that continuously pumped media containing nutrition and other molecules needed for cells to grow. The hydrogel and the pumping of media together creates a 3D structure and flow; two important parameters present in the lymph nodes where B-cell lymphomas normally reside.
In this type of dynamic setup, the growth was comparable to conventional static culturing methods as observed during our experiments. This indicates that this simple model has potential to be a starting point to create a MCL in vitro model to grow primary cells, which can help evaluate drug response in the clinics. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9029229
- author
- Lengquist, Alexandra LU
- supervisor
-
- Sara Ek LU
- Lavanya Lokhande LU
- organization
- course
- KIMM05 20201
- year
- 2020
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- Microfluidics, Hydrogel, Matrigel, Lymphoma, in vitro model
- language
- English
- id
- 9029229
- date added to LUP
- 2020-10-05 10:27:10
- date last changed
- 2020-10-05 10:27:10
@misc{9029229,
abstract = {{Cancer patients often show varying response when given the same treatment for the same cancer type. This is especially true for cancer types with high molecular heterogeneity such as B-cell lymphomas which is a haematological cancer subtype. Because of this varying treatment response, research is moving towards enabling personalized medicine where a treatment is selected for each individual patient. To enable personalized treatment in clinics many steps need to be made. In vitro models that mimic the in vivo environment can be used to culture primary patient samples. Using a previously published in vitro model for B cell lymphoma, published by Mannino et al (2018), this thesis project is aimed at creating a microfluidicsbased culture system that can potentially mimic the extracellular environment within lymph nodes. The objective is to develop a model for mantle cell lymphoma (MCL) which is a particularly aggressive B-cell lymphoma subtype and which has high diversity of response to currently available therapies. Our results show that it is possible to grow B- and T-cells in our constructed microfluidic setups and that the growth is of the same magnitude when compared to static cultures. This opens the possibility of creating a model that can be used in clinics to determine specific treatment methodology for mantle cell lymphoma patients.}},
author = {{Lengquist, Alexandra}},
language = {{eng}},
note = {{Student Paper}},
title = {{Microfluidic model for B-cell lymphoma}},
year = {{2020}},
}