Translating stem cells into ligaments for regenerative medicine

Funding Type: 
Early Translational III
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

In California, over 12,000 people will rupture their anterior cruciate ligament (ACL) this year. Most of these people will sacrifice one of their healthy ligaments in order to reconstruct the ACL in an effort to stabilize the knee and prevent arthritis. Even though the surgeries are usually successful at stabilizing the knee, most people who undergo this operation experience pain and a loss of function at the donor site. Therefore, it is extremely important to develop new clinical choices to replace damaged ligaments. We have recently developed the first engineered ligaments containing both the ligament and bone. The ligament is made from stem cells isolated from a patient’s bone marrow, while the bone is made from the same calcium phosphate that makes up our skeleton. The ligaments are completely tailorable in their size and shape. Over the past 3 years, we have improved the ligament grafts to the point that they are ready for testing in appropriate animal models. This proposal will allow us to finalize the conditions in which to grow the grafts before implantation and assess their function once implanted. Upon successful completion of this work we will be close to reaching our goal of engineering ligament grafts to treat the thousands of Californians who must reconstruct their ACL each year.

Statement of Benefit to California: 

Approximately 1 in 3,000 people in California will rupture their ACL this year and need it reconstructed. For patients with active professions, such as policemen, firemen, construction, and crop workers, ACL reconstruction will mean a minimum of 6-12 weeks out of work costing Californians millions of dollars. Currently, the only clinical option is to reconstruct the ACL using part of the patient’s healthy patellar or hamstrings tendon (autografts) or a ligament taken from a cadaver (allografts). There are serious drawbacks to both autografts and allografts including donor tendon rupture and a 3-fold greater incidence of failure, respectively. Successful engineering of ligaments from bone marrow stromal cells would provide a novel clinical option and may accelerate return to activity resulting in easier rehabilitation, less time and money lost to disability, and an improved quality of life for tens of thousands of Californians annually.