This project will develop and verify a microtissue engineered bioreactor platform to expand bone marrow cancer stem cells and create xenograft models using frozen MDS patient marrow cells. The project specific aims are: (1) Specific Aim 1: Microfluidic bioreactor for human HSC expansion from a low volume marrow sample; (2) Specific Aim 2: Genetically engineered scaffolds to recreate a MDS microenvironment ex vivo; and (3) Specific Aim 3: Ex vivo differentiation testing of MDS stem cells to predict leukemic transformation. The deliverable of the project will be a qualified bioreactor culture system and protocol to expand rare cells, such as pre-leukemic stem cells, from a small volume bone marrow biopsy tissue sample for use in prospective clinical trials.

Public Health Relevance

An engineered bone marrow stem cell bioreactor is proposed that continuously perfuses a 3D hydrogel scaffold for low volume marrow biopsy studies. The scaffold is customized to mimic a bone marrow cancer microenvironment by using genetically engineered stromal cells with the objective to expand pre- leukemic cells from patient bone marrow samples (which cannot otherwise grow ex vivo or in mouse xenografts) using this bioreactor system. Patient MDS cells grown in the scaffold will be tested for ex vivo growth and results will be correlated to patient outcomes as a companion model. This research can pave the way for immediate applications in prospective, companion clinical trials in MDS patients as well as using this small volume bioreactor platform for other rare bone marrow cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
2R01EB012521-08A1
Application #
9446640
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Rampulla, David
Project Start
2011-08-01
Project End
2022-05-31
Budget Start
2018-09-15
Budget End
2019-05-31
Support Year
8
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Rutgers University
Department
Social Sciences
Type
Schools of Arts and Sciences
DUNS #
001912864
City
Piscataway
State
NJ
Country
United States
Zip Code
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