tobacco plant 224.88.
(photo credit: William Rafti of the William Rafti Institute)
Natural human type I collagen is the most abundant protein in the human body, and the main protein in all connective tissue. Commercially produced collagen (pro-collagen) is used in surgical implants and many wound-healing devices in regenerative medicine. The current market for collagen-based medical devices in orthopedics and wound healing exceeds $30 billion annually worldwide. Commercial collagen is currently produced from farm animals such as cows and pigs as well as from human cadavers. These materials are prone to harbor human pathogens such as viruses or prions (Creutzfeldt-Jakob or “mad-cow” disease). Human cadavers are scarce, and for certain indications possesses serious ethical issues. Producing human recombinant type I pro-collagen requires the coordinated expression of five different genes.
Now Prof. Oded Shoseyov of the Hebrew University of Jerusalem’s Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture has produced a replica of human collagen from tobacco plants – an achievement with great commercial implications. Shoseyev has established the world’s only lab to report successful co-expression of all five essential genes in transgenic tobacco plants for the production of processed pro-collagen. Shoseyov’s invention has been patented, and the scientific findings behind it were published recently in the journal Biomacromolecules. He is one of the recipients of the Kaye Innovation Award for his work on synthetic collagen. (See New Worlds column on this page about the Kaye prizes.)
A $40 million company named CollPlant Ltd., of which Yissum is a shareholder, has been established based on patents and technology that were developed in his lab, and has raised $15 million to establish Israel’s first commercial molecular farming company. It is already manufacturing collagen-based products that have attracted collaborative commercial interest from companies in the US, Japan Europe and Israel. Shoseyov says the company collagen is not less expensive than animal-source collagen, but is safer and performs much better, since it is “virgin” collagen rather than “old or used” animal or cadaver collagen.
HUMAN EMBRYONIC STEM CELLS MOVE FORWARD
Yet another Kaye Innovation Award winner is Prof. Nissim Benvenisty of HU’s Silberman Institute of Life Sciences. He and his team were the first in the world to demonstrate in-vitro
differentiation of human embryonic stem cells (hESCs) and achieve the first directed differentiation and genetic manipulation of these cells. This work led to a patent on the directed differentiation of human embryonic stem cells, and is now at the center of industrial use of this research, which is aimed primarily at developing a stem cell-based approach to confront type 1 diabetes.
The main goal is to direct hESCs to differentiate into insulin-secreting pancreatic beta cells for transplantation into type 1 diabetes patients. This type, in which patients’ lives are dependent on the frequent injection of insulin, is an autoimmune disease caused by destruction and loss of function of beta cells in the pancreas. As a result, insulin is not produced, and blood glucose levels are not regulated. The disease can cause many complications, including heart disease, blindness, kidney disease and nerve damage.
Although insulin therapy has dramatically reduced mortality from diabetes, patients often succumb to the long-term complications. Transplantation of functional pancreatic cells represents one of the most promising approaches toward curing diabetes. However, this approach is now limited by a shortage of tissues, but hESCs could eventually offer an unlimited source of beta cells for transplantation once an effective differentiation protocol is developed.
A pluripotent (developmentally undefined) cell that may differentiate
in culture to all cell types is the “holy grail” of the study of
cellular differentiation and cell-based therapy. HESCs may give rise to
many cell types, such as nerve, muscle, liver, heart and blood, so they
promise to change the face of transplantation medicine. These cells may
eventually be used to treat a large number of diseases, including
Parkinson’s, diabetes, liver cirrhosis, heart failure and others. Over
the years, Benvenisty’s lab has made significant discoveries in the
field, showing for the first time in-vitro differentiation of hESCs and
generation of embryoid bodies – aggregates of cells derived from
embryonic stem cells. They also have been able to induce
differentiation of such cells by placing them next to developing chick
Benvenisty cautions that the hESC might be rejected by the body after
transplantation; his analysis of hESC immunogenicity has shown that
although undifferentiated ones express extremely low levels of
immunogenic (rejecting) molecules, that may increase when they
differentiate. Thus, hESCs will probably be a target for cell
rejection, and ways to overcome this issue should be further explored,
During the past decade, the research coming out of Benvenisty’s lab has
been published in over 50 papers, with many of the articles on hESCs
appearing as scientific journal cover stories. SCT-Stem Cell
Technologies Ltd. was founded in 2004 to capitalize on this experience
in research by HU and Haifa’s Technion-Israel Institute of Technology.