Novel therapeutic approaches to regulating the regenerative response in musculoskeletal tissues are based on the understanding of the processes involved, with each stage representing a possible target. Understanding the cells involved in these processes remains an important component. The cellular events in healing of tendon and bone have been extensively characterized and are known to involve several different cell types. However, the progenitor cells that actually contribute to the healing process have not been defined and therefore have never been specifically targeted in vivo. Multipotent cells have been isolated from several tissues including muscle, adipose, blood vessels, and bone marrow. Within these tissues, possible progenitor cells include myoblasts, activated satellite cells, differentiated skeletal muscle cells, vascular and non-vascular smooth muscle cells, pericytes, endothelial cells of developing and mature blood vessels, and bone marrow derived cells. Understanding the heritage of cells in postnatal musculoskeletal tissue repair will identify the progenitor cells as cellular targets for therapeutic approaches. We hypothesize that skeletal muscle satellite cells, pericytes, endothelial cells and bone marrow cells participate in the formation of musculoskeletal tissue such as heterotopic ossification, fracture healing and tendon repair and that cells from these sources will contribute to the new tenocytes and osteoblasts. We differentiated cells that can be identified both by their surface markers as well as by their lineage markings. With the use of this lineage tracing studies, our goal is to provide the first definitive evidence of the heritage of cells in postnatal tendon repair and bone formation and provide direct cellular targets for therapeutic approaches to regulating the regenerative response in these tissues. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
5R03AR052485-03
Application #
7216790
Study Section
Special Emphasis Panel (ZAR1-GHZ-D (J2))
Program Officer
Wang, Fei
Project Start
2005-04-01
Project End
2009-03-31
Budget Start
2007-04-01
Budget End
2009-03-31
Support Year
3
Fiscal Year
2007
Total Cost
$75,143
Indirect Cost
Name
University of Pennsylvania
Department
Orthopedics
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104