A novel three-dimensional stromal-based model forin vitrochemotherapy sensitivity testing of leukemia cells

Abstract

The disparate responses of leukemia cells to chemotherapy in vivo, compared to in vitro, is partly related to the interactions of leukemic cells and the 3 dimensional (3D) bone marrow stromal microenvironment. We investigated the effects of chemotherapy agents on leukemic cell lines co-cultured with human bone marrow mesenchymal stem cell (hu-BM-MSC) in 3D. Comparison was made to leukemic cells treated in suspension, or grown on a hu-BM-MSC monolayer (2D conditions). We demonstrated that leukemic cells cultured in 3D were more resistant to drug-induced apoptosis compared to cells cultured in 2D or in suspension. We also demonstrated significant differences in leukemic cell response to chemotherapy using different leukemic cell lines cultured in 3D. We suggest that the differential responses to chemotherapy in 3D may be related to the expression of N-cadherin in the co-culture system. This unique model provides an opportunity to study leukemic cell responses to chemotherapy in 3D.

Three dimensionalde novomicro bone marrow and its versatile application in drug screening and regenerative medicine

“…34 Not only does this 3D system mimic the structure, it also offers the supporting microenvironment required by the leukemia cells. In this 3D system, leukemia cells are more chemo-resistant and proliferative due to this supporting niche.…”

“…Hence, the limitations imposed by conventional animal models and culturing of B/BM stem cell lines in petri dishes restrict our investigations aimed at furthering the understanding of disease processes and hinder the development of high throughput drug screening protocols. 34 Recent developments including 3D printing techniques, biocompatible and biodegradable materials, together with a deeper understanding of the importance of complex dialogues between different components of B/BM, are now fueling the emergence of 3D artificial BM. A 3D BM system induced by biologically modified degradable carrier scaffolds (made of natural or synthetic biocompatible and biodegradable materials) is composed of de novo generated hematopoietic stromal cells, associated growth factors/ ECM proteins, and calcified bones.…”

In Vitro Modeling of Tissue-Specific 3D Microenvironments and Possibile Application to Pediatric Cancer Research

“…This is one of the major issues in designing a 3D model for chemotherapy, since the 3D model need to allow media components and cytotoxic agents to diffuse freely to target cells. An innovative 3D model was set up by Usuludin and coworkers [156]. They developed a hematopoietic coculture system using the hollow fiber bioreactor (HFBR, purchase from FiberCell Systems Inc., Federick, MD, USA).…”

3D multicellular models reflect the efficiency of MSC-directed enzyme/prodrug treatment

“…Previous report from Harma et al showed that specific small molecule inhibitors targeted against PI3-kinase blocked invasive cell growth more effectively in 3D than in 2D monolayer culture of prostate cancer cells [24]. Aljitawi et al compared the chemosensitivity of leukemia cells in a novel 3D stromal-based model and showed on contrary increased chemoresistance of the leukemic cells cocultured with stromal cells in non-adherent conditions [25]. Further correlations and investigation of different non-adherent models of cell proliferation will be useful for predictive testing of anti-cancer and anti-metastatic compounds.…”