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Direct and Bone Marrow Mediated Effects of Adipose Stem Cells in Emphysema

Award Number: R01HL105772
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/21/2015
PERIOD OF PERFORMANCE END DATE: 11/30/2016

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Direct and Bone Marrow Mediated Effects of Adipose Stem Cells in Emphysema - DESCRIPTION (provided by applicant): Pulmonary emphysema is a prevalent lung disease defined by permanent enlargement of airspaces, but also associated with systemic effects on organs that include the bone marrow and the cardiovascular system. Little is known about the mechanisms of systemic illness in emphysema and their impact, if any, on the lung disease. The lung destruction, clinically apparent after years of cigarette smoking has been attributed to protease-antiprotease imbalance, chronic inflammation, oxidative stress, and excessive alveolar cell death with loss of pulmonary capillaries that support the alveolar unit. We demonstrated that pluripotent cells contained in adipose stroma, called adipose stem or stromal cells promote capillary growth and limit ischemic tissue damage in models of acute skeletal muscle, myocardial, and cerebral ischemia and these salutary effects are mediated by angiogenic and anti-apoptotic paracrine factors. Given the feasibility of obtaining these stem cells, requiring no or limited ex vivo expansion, we tested the effect of adipose stem cells on cigarette smoke-induced murine emphysema. This form of regenerative treatment resulted in preservation of alveolar surface area and marked protection of the bone marrow from the suppressive effects of smoke on the number and cycling of multiple lineages of progenitor cells. We therefore generated the novel hypothesis that treatment with adipose stem cells will ameliorate the alveolar structural loss induced by cigarette smoking by decreasing lung structural cell death and reducing the loss of bone marrow-derived progenitor cells. To test this novel promising therapy for emphysema and to advance understanding of the crosstalk between the lung and bone marrow in emphysema development, we focused on 3 specific aims: 1. to determine the efficacy of adipose stem cells to limit cigarette smoke-induced murine emphysema; 2. to determine the effect of adipose stem cell treatment on the cigarette smoke-induced bone marrow-derived progenitor cell loss and to establish its importance to the development of emphysema; 3. to establish the role of adipose stem cell-secreted paracrine factors VEGF, HGF, and TSG-6 in the inhibition of lung destruction and of bone marrow hypoplasia induced by adipose stem cell exposure. We have assembled a multidisciplinary team with expertise in emphysema pathobiology, adipose stem cell-, vascular-, and bone marrow stem cell-biology to investigate the proposed comprehensive research plan. If completed, this work will determine the effectiveness, optimal approach, and mechanisms of adult, thus generally ethically accepted, adipose stem cell therapy in a relevant emphysema model, and will accelerate its implementation as a potential therapeutic approach in COPD.


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: 2017 ( Subtotal = $0 )
2017	2015	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	5	2/21/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $0 )
2016	2015	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Lung Diseases Research	001	4	12/18/2015	NON-COMPETING CONTINUATION	$22,745
2016	2015	NATIONAL JEWISH HEALTH	1400 JACKSON STREET	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	5	12/17/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$22,745
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $384,150 )
2015	2015	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Lung Diseases Research	000	4	11/21/2014	NON-COMPETING CONTINUATION	$351,000
2015	2015	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Lung Diseases Research	001	4	2/26/2015	NON-COMPETING CONTINUATION	$33,150
2015	2015	NATIONAL JEWISH HEALTH	1400 JACKSON STREET	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	002	5	8/14/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$289,883
2015	2015	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Lung Diseases Research	003	4	8/14/2015	NON-COMPETING CONTINUATION	-$289,883
														Subtotal = $384,150

Issue Date FY: 2014 ( Subtotal = $382,200 )
2014	2014	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Lung Diseases Research	000	3	2/6/2014	NON-COMPETING CONTINUATION	$351,000
2014	2014	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Lung Diseases Research	001	3	2/27/2014	NON-COMPETING CONTINUATION	$31,200
														Subtotal = $382,200

Issue Date FY: 2013 ( Subtotal = $371,280 )
2013	2013	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Lung Diseases Research	001	2	6/25/2013	NON-COMPETING CONTINUATION	$20,280
2013	2013	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Lung Diseases Research	000	2	11/19/2012	NON-COMPETING CONTINUATION	$351,000
														Subtotal = $371,280

Issue Date FY: 2012 ( Subtotal = $380,140 )
2012	2012	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Lung Diseases Research	000	1	12/2/2011	NEW	$380,140
														Subtotal = $380,140

Grand Total All Awards = $1,517,770

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Direct and Bone Marrow Mediated Effects of Adipose Stem Cells in Emphysema

Award Number: R01HL105772

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/21/2015

PERIOD OF PERFORMANCE END DATE: 11/30/2016

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