Clinical transplantation of hematopoietic stem cells (HSCs) has been used to treat a broad range of hematologic, immune, genetic, and neoplastic diseases. A major obstacle for this treatment is the limited availability of HSCs. In vitro expansion of HSCs can solve the issue by generating quality-controlled, off-the-shelf HSC products. However, to date, it remains difficult to expand, or even maintain HSCs in vitro. Here, we propose to create micro-engineered artificial stromal cells that offer the spatial presentation of stromal factors necessary for HSC maintenance and expansion. Our central hypothesis is that spatial presentation of HSC niche signals by stromal cells is critical for HSC maintenance and expansion. We will develop biomimicry ?artificial stromal cell? platforms with more realistic in vivo features of HSC niches, with mouse HSCs as a model. We will carry out our study by a) evaluating the spatial organization of membrane-bound signals and its impact on HSC maintenance and expansion at subcellular and cellular levels, and b) evaluating the maintenance and expansion of HSCs on a microparticle-based platform of artificial stromal cells. The proposed study will provide novel insights and concepts into the signaling dynamics of HSC with its stromal microenvironment. Our long term goal is to translate our findings to human HSCs and their large-scale production to meet the demand of clinical bone marrow transplantations. The knowledge developed here can also be extended to a broad range of tissue and organ systems with stem cell-stromal cell interactions.

Public Health Relevance

Clinical transplantation of hematopoietic stem cells (HSCs) can treat a wide range of diseases related to the blood and immune systems. A major obstacle for this treatment is the limited availability of HSCs. We propose to create micro-engineered artificial stromal cells that can controllably maintain and expand HSCs in vitro. This project will broadly impact our understanding of HSC interactions with its stromal microenvironment and other stem cell-stromal cell interactions. It can also be translated to the large-scale production of human HSCs to meet the demand of clinical bone marrow transplantations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB024748-01
Application #
9375817
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Mamaghani, Shadi
Project Start
2017-08-01
Project End
2020-04-30
Budget Start
2017-08-01
Budget End
2018-04-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Southern California
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90033
Ando, Yuta; Ta, Hoang P; Yen, Daniel P et al. (2017) A Microdevice Platform Recapitulating Hypoxic Tumor Microenvironments. Sci Rep 7:15233