Abstract

The overall goal of this project is to optimize and deploy a bioengineered implant to increase the apparent space for transplanted hematopoietic stem cells during states of marrow failure. The project specific aims are: (1) Identify critical manufacturing parameters of the implant. (2) Design a clinical protocol for use of implants to rescue bone marrow failure, and (3) Image-guided monitoring of the implant therapy. Our expected contribution is the development of a novel bioengineered bone marrow patch that is significant because the protocols developed here could rescue thousands of patients who die from marrow failure by making marrow transplantation more efficient.

Public Health Relevance

We have developed stromal cell-laden 3D microfabricated biomaterials (referred to as patches) that mimic the hematopoietic inductive microenvironment of the bone marrow. We now plan to evaluate the implantation of these patches as an approach to increase the effective space for hematopoietic stem cell engraftment during marrow failure. The creation, therapeutic testing, and monitoring of patch therapy is proposed to translate pre-clinical studies towards human trials.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB012521-02
Application #
8293003
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Hunziker, Rosemarie
Project Start
2011-08-01
Project End
2017-07-31
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
2
Fiscal Year
2012
Total Cost
$572,709
Indirect Cost
$207,356

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Mukundan, Shilpaa; Sharma, Kriti; Honselmann, Kim et al. (2018) Image-Based Profiling of Patient-Derived Pancreatic Tumor-Stromal Cell Interactions Within a Micropatterned Tumor Model. Technol Cancer Res Treat 17:1533033818803632
Li, Matthew; Chin, Ling-Yee; Shukor, Syukri et al. (2018) Closed loop bioreactor system for the ex vivo expansion of human T cells. Cytotherapy :
Khong, Danika; Li, Matthew; Singleton, Amy et al. (2018) Orthogonal potency analysis of mesenchymal stromal cell function during ex vivo expansion. Exp Cell Res 362:102-110
Mukundan, Shilpaa; Guan, Dongli; Singleton, Amy et al. (2018) Artificial T Cell Mimetics to Combat Melanoma Tumor Growth. Am J Adv Drug Deliv 6:21-32
Li, Matthew; Khong, Danika; Chin, Ling-Yee et al. (2018) Therapeutic Delivery Specifications Identified Through Compartmental Analysis of a Mesenchymal Stromal Cell-Immune Reaction. Sci Rep 8:6816
Tosi, Lorenzo; Sridhara, Viswanadham; Yang, Yunlong et al. (2017) Long-adapter single-strand oligonucleotide probes for the massively multiplexed cloning of kilobase genome regions. Nat Biomed Eng 1:
Singleton, Amy; Khong, Danika; Chin, Ling-Yee et al. (2017) An engineered biomarker system to monitor and modulate immune clearance of cell therapies. Cytotherapy 19:1537-1545
Lee, Jungwoo; Heckl, Dirk; Parekkadan, Biju (2016) Multiple genetically engineered humanized microenvironments in a single mouse. Biomater Res 20:19
Shen, Keyue; Luk, Samantha; Elman, Jessica et al. (2016) Suicide Gene-Engineered Stromal Cells Reveal a Dynamic Regulation of Cancer Metastasis. Sci Rep 6:21239
Lee, Jungwoo; Kohl, Nathaniel; Shanbhang, Sachin et al. (2015) Scaffold-integrated microchips for end-to-end in vitro tumor cell attachment and xenograft formation. Technology (Singap World Sci) 3:179-188

Showing the most recent 10 out of 22 publications