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Biomimetic Artificial Niche for Hematopoietic Stem Cell Expansion

Award Number: F32HL123224
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/02/2014
PERIOD OF PERFORMANCE END DATE: 07/01/2016

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Biomimetic Artificial Niche for Hematopoietic Stem Cell Expansion - DESCRIPTION (provided by applicant): Each year, over 30,000 patients suffering from hematological diseases such as leukemia, lymphoma, multiple myeloma, and severe aplastic anemia are treated with high-dose chemotherapy followed by hematopoietic stem cell (HSC) transplantations. The ability of HSCs to reconstitute all blood lineages post transplantation can be life-saving for these patients. However, their need is severely outweighed by their availability due to the difficulty in finding a suitable donor match coupled with their low expansion potential ex-vivo. A variety of culture conditions have been evaluated for in vitro expansion of HSCs but have yielded limited success due to an increase in differentiation, loss of stemness and promotion of cell cycle abnormalities in culture. Thus, this project aims to develop novel biomimetic biomaterial substrates and harbor the innate ability of co-existing niche cells to promote HSC expansion in vitro. Aim 1 will develop a biomaterial substrate to emulate the native bone marrow extracellular matrix environment and promote HSC expansion in vitro. Aim 2 will investigate if alternative sources of Nestin positive MSCs exist, which can be harnessed towards the expansion of HSCs in vitro. Finally, Aim 3 will determine the role of additional candidate niche cells in promoting HSC expansion in vitro. This proposal will characterize the molecular mechanisms behind HSC expansion due to the effects of the biomaterial or other candidate niche cells in culture with HSCs by analyzing cell surface receptors, cytoskeleton changes, soluble factors, genetic changes and associated intracellular pathways. Innovative methods for promoting HSC expansion could be used for life-saving transplantations to significantly impact the prognosis of patients with hematological malignancies. Additionally, this system can serve as a model for studying niche cell-cell interactions, cell-matrix interactions, drug screening and genetic diseases. These studies will significantly contribute to the knowledge base of the bone marrow niche microenvironment and potentially lead to the development of new patient therapies so they can live longer and more fulfilling lives.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Blood Diseases and Resources Research	001	3	11/17/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,146
2018	2014	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Blood Diseases and Resources Research	000	1	11/17/2017	NEW	-$1,146
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = -$12,446 )
2016	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Blood Diseases and Resources Research	000	2	11/18/2015	NON-COMPETING CONTINUATION	-$56,042
2016	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Blood Diseases and Resources Research	001	3	11/19/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$56,042
2016	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Blood Diseases and Resources Research	002	3	8/18/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$12,446
														Subtotal = -$12,446

Issue Date FY: 2015 ( Subtotal = $56,042 )
2015	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Blood Diseases and Resources Research	000	2	8/3/2015	NON-COMPETING CONTINUATION	$56,042
														Subtotal = $56,042

Issue Date FY: 2014 ( Subtotal = $53,282 )
2014	2014	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Blood Diseases and Resources Research	000	1	9/1/2014	NEW	$0
2014	2014	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Blood Diseases and Resources Research	001	1	9/1/2014	NEW	$53,282
														Subtotal = $53,282

Grand Total All Awards = $96,878

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Biomimetic Artificial Niche for Hematopoietic Stem Cell Expansion

Award Number: F32HL123224

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/02/2014

PERIOD OF PERFORMANCE END DATE: 07/01/2016

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