Improvement of Induced Pluripotent Stem Cell as a Tool for Clinical use in Cardiology

Funding Type: 
Tools and Technologies I
Grant Number: 
RT1-01127
Investigator: 
ICOC Funds Committed: 
$0
Public Abstract: 
Very recently, November of 2007 , a discovery was made that could broaden the prospects of rapid development of stem cell therapies without the ethical barriers. It is called “Induced Pluripotent Stem Cells” ( iPS) or direct reprogramming of adult cells, turning them back into embryonic like cells without involving any embryos. These cells could be used as stem cells that would turn into any type of cell required to treat human diseases. However we are not there yet. iPS cells have been produced by the use of retro viruses which could induce tumors in the recipient. At least one of the transcription factors used was cancer causing. Further the iPS cells have not been compared to other studies of adult stem cells as therapy for important diseases. We need to have a reliable method to make iPS effective for human use. So far the main source of donor cells has been skin cells ( fibroblasts) . To be practical, medicine will need to obtain cels from easily available sources. The goal of our proposal is to develop iPS as a tool that can be easily produced in large quantities and used safely and effectively in human diseases. We propose to avoid tumorogenesis by delivering the necessary and sufficient transcription factors to reprogram adult cells by a non retro viral vector and two non viral delivery systems. 1) We will deliver selected transcription factors in adeno-associated viral vectors (AAV). These vectors have been used in human trials and are safe and non cancerous. 2) We will test a cell membrane penetrating protein ( VP22) to deliver the factors effectively. These novel methods could allow us to produce a large quanity of the critical factors and then mix them in the appropriate cocktail to produce many iPS cells ready for use in humans. Further, we will apply the techniques to three different sources of human cells that are easily obtained by standard methods, skin fibroblasts, adipocytes ( fat cells ) and bone marrow stromal stem cells. To test that the stem cells derived from iPS made by these methods are therapeutic and clinically relevant we will test the human stem cells in a model of heart failure. The proposal could have several benefits. First we will define a way of safely producing pluripotent stem cells for human use. Second we will test them in cardiovascular disease.
Statement of Benefit to California: 
The State of California and its citizens have led the world in investing in stem cell research. They are looking for benefits both to patients health and to business in creating new industries that provide employment and reap the economic benefits of their investment. Originally CIRM addressed research on human embryonic stem cells because of the federal government ban on federal funding for stem cell research. Very recently, November of 2007 , a discovery was made that could change this focus and broaden the prospects of rapid development of stem cell therapies without the ethical barriers. It is called ìInduced Pluripotent Stem Cellsî ( iPS) or direct reprogramming of adult cells turning them back into embryonic like cells without involving any embryos. These cellscould be used as stem cells that would turn into any type of cell required to treat human diseases. However we are not there yet. iPS cells have been produced by the use of retro viruses which could induce tumors in the recipient. At least one of the transcription factors used was cancer causing. Further the iPS cells have not been compared to other studies of adult stem cells as therapy for important diseases. We need to have a reliable method to make iPS effective for human use. So far the main source o donor cells has been skin cells ( fibroblasts) . To be practical, medicine will need to obtain cells from easily available sources. The goal of our proposal is to develop iPS as a tool that can be easily produced in large quantities and used safely and effectively in human diseases. We propose to avoid tumorogenesis by delivering the necessary and sufficient transcription factors to reprogram adult cells by a non retro viral vector and two non viral delivery systems. 1) We will deliver selected transcription factors in adeno-associated viral vectors (AAV). These vectors have been used in human trials and are safe and non cancerous. 2) We will test a cell membrane penetrating protein ( VP22) to deliver the factors effectively. The VP-22 combined with AAV could allow us to produce a lage quantitiy of these critical factors and then mix them in the appropriate cocktail to produce many iPS cells ready for use in humans. Further, we will apply the techniques to three different sources of human cells that are easily obtained by standard methods, skin fibroblasts, adipocytes ( fat cells ) and bone marrow stromal stem cells. To test that the stem cells derived from iPS made by these methods are therapeutic and clinically relevant we will test the human stem cells in an animal model of heart ailure. The proposal could have several benefits for California. First we will define a way of safely producing pluipotent stem cells for human use. Second we will test them in cardiovascular disease . Third we may develop a new business in California working with such companies as [REDACTED] to produce stem cells.

© 2013 California Institute for Regenerative Medicine