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AGING EFFECTS ON CELLULAR THERAPY FOR HEART FAILURE

Award Number: R01AG027263
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2008
PERIOD OF PERFORMANCE END DATE: 06/30/2012

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AGING EFFECTS ON CELLULAR THERAPY FOR HEART FAILURE - DESCRIPTION (provided by applicant): The long term objective of this project is to design a strategy(s) to improve cardiac function in the aged population after myocardial infarction (Ml). The impaired angiogenic capability of the aged heart after Ml may be due to diminished angiogenesis (sprouting of preexisting vessels) and/or vasculogenesis (incorporation of progenitor cells in the newly formed vessels). In contrast to the known impaired angiogenesis, vasculogenesis which is mediated by circulating and/or resident tissue EPCs, is less characterized in the aged heart after Ml. Therefore, determining the role of EPCs in ischemia-induced neovascularization is the main focus of this application. This will provide the foundation to develop an EPC-based strategy to improve cardiac function after Ml in the aged. These EPCs may deliver the needed cytokines for vascularization. Three routes of cell delivery are utilized, intravenous injection, direct injection into the infarct, and delivery using a 3-D collagen scaffold grafted onto the myocardium after Ml. The scaffold approach serves as a model to study cardiac angiogenesis in vivo, and to locally deliver stem cells and/or angiogenic factors to the injured myocardium. Our data, using Brown Norway Fisher 344 cross (BNXF344) rats at different ages (6 weeks, 6 months, and 24 months), indicate that the scaffold initially stabilizes the infarct, promotes angiogenesis, and is replaced by viable tissue. Based on these results, and the current literature, our hypothesis is that cell transplantation of genetically-modified EPCs will enhance ischemia-induced vascularization and will lead to improved cardiac function in the aged after Ml. To test this hypothesis, BNXF344 rat model will be used to determine if the depressed ischemia-induced neovascularization in the aged can be improved using EPC; to elucidate the mechanisms of age-mediated diminished EPCs-contribution to this process; and to determine if overexpression of CXCR4 on EPCs enhances stem cell recruitment to the infarct leading to improve vasculogenesis/cardiac function. Our research will help fill specific gaps in our present knowledge regarding the greater susceptibility to loss of cardiac function after Ml in the elderly and methods to assist recovery. These gaps include: no established treatment exits for the diminished angiogenic capability of the aged heart after Ml; the specific contribution of progenitor cells in this process is unknown; and aging effects on EPCs function are unclear


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: 2011 ( Subtotal = $330,731 )
2011	2011	SUN HEALTH RESEARCH INSTITUTE	P.O. BOX 1278	SUN CITY	AZ	85372	MARICOPA	USA	Aging Research	000	6	6/23/2011	NON-COMPETING CONTINUATION	$330,731
														Subtotal = $330,731

Issue Date FY: 2010 ( Subtotal = $344,081 )
2010	2010	SUN HEALTH RESEARCH INSTITUTE	P.O. BOX 1278	SUN CITY	AZ	85372	MARICOPA	USA	Aging Research	000	5	6/21/2010	NON-COMPETING CONTINUATION	$344,081
														Subtotal = $344,081

Issue Date FY: 2009 ( Subtotal = $347,557 )
2009	2009	SUN HEALTH RESEARCH INSTITUTE	P.O. BOX 1278	SUN CITY	AZ	85372	MARICOPA	USA	Aging Research	000	4	6/18/2009	NON-COMPETING CONTINUATION	$347,557
														Subtotal = $347,557

Issue Date FY: 2008 ( Subtotal = $347,557 )
2008	2008	SUN HEALTH RESEARCH INSTITUTE	POST OFFICE BOX 1278	SUN CITY	AZ	85372	MARICOPA	USA	Aging Research	000	3	6/6/2008	NON-COMPETING CONTINUATION	$347,557
														Subtotal = $347,557

Issue Date FY: 2007 ( Subtotal = $309,550 )
2007	2007	UNIVERSITY OF ARIZONA, COLLEGE OF MEDICINE	1450 NORTH CHERRY AVENUE	TUCSON	AZ	85721	PIMA	USA	Aging Research	000	1	6/21/2007	NEW	$309,550
														Subtotal = $309,550

Grand Total All Awards = $1,679,476

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AGING EFFECTS ON CELLULAR THERAPY FOR HEART FAILURE

Award Number: R01AG027263

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2008

PERIOD OF PERFORMANCE END DATE: 06/30/2012

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