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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB012521-03
Application #
8469758
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
2013-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$582,897
Indirect Cost
$213,334
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Fletcher, Anne L; Elman, Jessica S; Astarita, Jillian et al. (2014) Lymph node fibroblastic reticular cell transplants show robust therapeutic efficacy in high-mortality murine sepsis. Sci Transl Med 6:249ra109
Elman, Jessica S; Li, Matthew; Wang, Fangjing et al. (2014) A comparison of adipose and bone marrow-derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation. J Inflamm (Lond) 11:1
Shen, Keyue; Luk, Samantha; Hicks, Daniel F et al. (2014) Resolving cancer-stroma interfacial signalling and interventions with micropatterned tumour-stromal assays. Nat Commun 5:5662
Milwid, Jack M; Elman, Jessica S; Li, Matthew et al. (2014) Enriched protein screening of human bone marrow mesenchymal stromal cell secretions reveals MFAP5 and PENK as novel IL-10 modulators. Mol Ther 22:999-1007
Shen, Keyue; Lee, Jungwoo; Yarmush, Martin L et al. (2014) Microcavity substrates casted from self-assembled microsphere monolayers for spheroid cell culture. Biomed Microdevices 16:609-15
Elman, Jessica S; Murray, Ryan C; Murray, Ryan M et al. (2014) Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells. PLoS One 9:e89882
Kam, L C; Shen, K; Dustin, M L (2013) Micro- and nanoscale engineering of cell signaling. Annu Rev Biomed Eng 15:305-26
Lee, Jungwoo; Wang, Jennifer B; Bersani, Francesca et al. (2013) Capture and printing of fixed stromal cell membranes for bioactive display on PDMS surfaces. Langmuir 29:10611-6