Abstract

This proposal is for basic research on the adult stem cells from bone marrow stroma referred to as mesenchymal stem cells or marrow stromal cells (MSCs). The overall aims of the proposal are: (a) to improve our understanding of the basic biology of human MSCs (hMSCs); (b) to develop new protocols for the ex vivo expansion of hMSCs and (c) to develop ex vivo and in vivo assays for the cells that will be of value for both further basic research with the cells and for their potential clinical applications to diseases of lung.
The Specific Aims are: (1) Elucidate the molecular events that permit and enhance ex vivo expansion of hMSCs. (2) Develop an ex vivo assay for the potential of hMSCs to repair injured lung by co-culturing hMSCs with lung cells that have been damaged by heat-shock and hypoxia. (3) Develop an in vivo assay for engraftment and differentiation of hMSCs to sites of tissue injury in lung. (4) Identify the properties of hMSCs that enhance their engraftment to specific sites of tissue injury in lung.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL073252-04
Application #
7112297
Study Section
Special Emphasis Panel (ZHL1-CSR-J (F2))
Program Officer
Berberich, Mary Anne
Project Start
2003-09-30
Project End
2008-07-31
Budget Start
2006-08-18
Budget End
2008-07-31
Support Year
4
Fiscal Year
2006
Total Cost
$362,526
Indirect Cost

  Institution

Name
Tulane University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118

  Publications

Ohkouchi, Shinya; Block, Gregory J; Katsha, Ahmed M et al. (2012) Mesenchymal stromal cells protect cancer cells from ROS-induced apoptosis and enhance the Warburg effect by secreting STC1. Mol Ther 20:417-23
Block, Gregory J; Ohkouchi, Shinya; Fung, France et al. (2009) Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1. Stem Cells 27:670-681
Lee, Ryang Hwa; Seo, Min Jeong; Pulin, Andrey A et al. (2009) The CD34-like protein PODXL and alpha6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice. Blood 113:816-26
Lee, Ryang Hwa; Pulin, Andrey A; Seo, Min Jeong et al. (2009) Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 5:54-63
Larson, Benjamin L; Ylostalo, Joni; Prockop, Darwin J (2008) Human multipotent stromal cells undergo sharp transition from division to development in culture. Stem Cells 26:193-201
Hung, Shih-Chieh; Pochampally, Radhika R; Hsu, Shu-Ching et al. (2007) Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo. PLoS One 2:e416
Spees, Jeffrey L; Pociask, Derek A; Sullivan, Deborah E et al. (2007) Engraftment of bone marrow progenitor cells in a rat model of asbestos-induced pulmonary fibrosis. Am J Respir Crit Care Med 176:385-94
Prockop, Darwin J; Olson, Scott D (2007) Clinical trials with adult stem/progenitor cells for tissue repair: let's not overlook some essential precautions. Blood 109:3147-51
Spees, Jeffrey L; Olson, Scott D; Whitney, Mandolin J et al. (2006) Mitochondrial transfer between cells can rescue aerobic respiration. Proc Natl Acad Sci U S A 103:1283-8
Wang, Guoshun; Bunnell, Bruce A; Painter, Richard G et al. (2005) Adult stem cells from bone marrow stroma differentiate into airway epithelial cells: potential therapy for cystic fibrosis. Proc Natl Acad Sci U S A 102:186-91

Showing the most recent 10 out of 11 publications