Adult tissue-derived mesenchymal stromal cells (MSC) have demonstrated promise in treating various pathologies including myocardial infarction, graft versus host disease and other tissue injuries such refractory wounds. Much of current work on MSC-based therapies consists of the development of cell entrapment matrix to control cell function and fate after implantation. While MSC had shown to have immunomodulatory properties, the impact of the MSC-encapsulated biomatrix on the host macrophage immunophenotype and host foreign body reaction is less clear. We hypothesize that adult, human bone marrow-derived MSC (BM- MSC) that are encapsulated into a 3-D biomaterial will preferentially modulate the polarization of host primary macrophages from a pro-inflammatory state towards a pro-healing and anti-inflammatory phenotype. A clear understanding of this three-way interaction between encapsulated MSC, macrophages, and biomaterial using primary human cells is required for the development of effective MSC-hydrogel strategies in cell-based regenerative medicine. To achieve this, we will: (1) formulate well-characterized biomaterials with improved biomechanic properties including strength and lack of contraction over commercially-available cell-delivery matrices for BM-MSC encapsulation;(2) assess the immunophenotype of blood-derived primary macrophages as modulated by biomaterial-entrapped BM-MSC in 3-D co-cultures;(3) confirm the ability of 3-D biomaterial- entrapped BM-MSC to recruit and modulate macrophage pro-healing phenotype in a wound model.

Public Health Relevance

Regenerative medicine holds much promise for various pathologies including cardiovascular diseases, traumatic tissue injuries and age related pathologies [1]. While much of current research focuses on developing biomaterials for mesenchymal stromal cell entrapment to control cell fate, little is known about the impact of this cell/biomaterial construct on the host foreign body reaction and macrophage activity, which has a direct impact on the downstream wound healing cascade [2-3]. A clear understanding of this three-way interaction between encapsulated MSC, macrophages, and biomaterial using primary human cells is required for the development of effective MSC-hydrogel strategies in cell-based regenerative medicine for wound healing.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL115482-02
Application #
8714037
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Mitchell, Phyllis
Project Start
2013-08-01
Project End
2015-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$217,196
Indirect Cost
$70,196
Name
University of Wisconsin Madison
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Cohen, Hannah Caitlin; Lieberthal, Tyler Jacob; Kao, W John (2014) Poly(ethylene glycol)-containing hydrogels promote the release of primary granules from human blood-derived polymorphonuclear leukocytes. J Biomed Mater Res A 102:4252-61