Stem Cells for Vascular Tissue Regeneration

Funding Type: 
Disease Team Planning
Grant Number: 
DT1-00702
Investigator: 
ICOC Funds Committed: 
$0
oldStatus: 
Closed
Public Abstract: 
The goals of this proposal are to establish adult and embryonic cell lines and construct cellular vascular grafts to treat peripheral vascular diseases (PVD), a common condition that affects approximately ten million adults in the U.S. Vascular diseases can be caused by atherosclerosis and aneurysm. Advanced atherosclerosis can cause diseases in different organs such as stroke, heart attacks, leg pain, deficient wound healing and ulcers. When the vascular disease involves multiple areas or a long segment of an artery, bypass surgery may be necessary. In the U.S., about 500,000 bypass surgeries are performed each year, with about half of which for PVD treatment, In this project, we will focus on developing vascular grafts using stem cells to treat PVD, with the aim of reaching clinical trials in 5 years. The technologies developed in this project could also be used to treat vascular diseases in heart and brain in the future. For bypass surgery, autologous vein (or artery) graft is the only small-diameter choice for clinical use. However, harvesting autologous graft involves additional surgery and complications at donor site. In addition, it is difficult to find healthy and appropriate vein (or artery) graft in some patients. Tissue engineering of small-diameter blood vessels is a promising approach. Since human vascular cells are difficult to expand for cell therapies, we propose to use mesenchymal stem cells (MSCs) and embryonic stem cell (ESCs)-derived progenitor cells as cell sources for vascular graft construction. We will seek to establish MSCs or ESC-derived progenitor cells with low immune responses, and use short-term immunosuppression as needed to prevent graft rejection. Our research will advance stem cell-derived therapy for vascular diseases and meet CIRM’s primary goal for the Disease Team Initiative. With our expertise and established technologies, it is likely that cellular vascular grafts seeded with stem cells/progenitor cells can lead to clinical studies in 5 years, which will provide new solutions to bypass surgery and benefit patients in the near future. These unmet challenges required a multidisciplinary team approach. We will assemble a team including bioengineers, stem cell biologists, vascular biologists, immunologists, clinicians and industry partners from multiple institutions, define the milestones and a full proposal, and facilitate the transfer of cellular vascular graft technologies to clinical studies.
Statement of Benefit to California: 
Vascular diseases can be caused by atherosclerosis and aneurysm. Advanced atherosclerosis can cause diseases in different organs such as stroke, heart attacks, leg pain, deficient wound healing and ulcers. When the vascular disease involves multiple areas or a long segment of an artery, bypass surgery may be necessary. In the U.S., about 500,000 bypass surgeries are performed each year, with about half of which for peripheral vascular diseases (PVD), a common condition that affects approximately ten million adults in the U.S. In this project, we will focus on developing vascular grafts using stem cells to treat PVD, with the aim of reaching clinical trials in 5 years. The technologies developed in this project could also be used to treat vascular diseases in heart and brain in the future. For bypass surgery, autologous vein (or artery) graft is the only small-diameter choice for clinical use. However, harvesting autologous graft involves additional surgery and complications at donor site. In addition, it is difficult to find healthy and appropriate vein (or artery) graft in some patients. Our approach can be used for allogeneic transplantation and are available off-the-shelf. We will seek to establish stem cell lines with low immune responses, and use short-term immunosuppression as needed to prevent graft rejection. Our research will advance stem cell-derived therapy for vascular diseases and meet CIRM’s primary goal for the Disease Team Initiative. With our expertise and established technologies, it is likely that cellular vascular grafts seeded with stem cells/progenitor cells can lead to clinical studies in 5 years, which will provide new solutions to bypass surgery and benefit patients in the near future.

© 2013 California Institute for Regenerative Medicine