A specialist in the biology of stem cells, Dr. Dafna Benayahu is attempting to develop a “lab on a chip” as her part of CellPROM.An Israeli team led by Dr. Dafna Benayahu of Tel Aviv University’s Sackler Faculty of Medicine is working with 27 other research groups from throughout Europe to revolutionize medical technology. Their goal in the five-year project is to develop the nano-scale tools needed to create a ’tissue machine’ – a device using stem cells that could produce, for the first time, a specific population of cells or tissue needed to heal a variety of ailments.
“Imagine that we could transplant into a patient’s body new cartilage or bone to reverse spinal cord damage, or heart muscle tissue to repair a damaged heart,” says Benayahu of the Department of Cell and Developmental Biology. “The research we’re doing could turn that vision into reality.”
The project, being supported by the European Union at a cost of 30 million euro, is called ‘CellPROM,’ short for ‘cell programming.’ Scientists already know how to take individual stem cells, nature’s template cell, and program them to turn into one or another kind of tissue. CellPROM strives to lay the scientific foundations for accelerating and automating this process on a large and industrially viable scale.
The kind of stem cells being studied are not embryonic, but rather adult stem cells, which are found in bone marrow.
“Using the adult type helps us bypass the ethical issues associated with embryonic stem cells,” explains Benayahu. “In addition, growing tissues based on a patient’s own stem cells could significantly lessen the body’s rejection of that tissue when it is transplanted back into the patient,” she says.
A specialist in the biology of stem cells, Benayahu is attempting to develop a “lab on a chip” as her part of CellPROM, together with microsystems expert Prof. Yosi Shacham of TAU’s Research Institute for Nanoscience and Nanotechnology.
The chip needs to automate the process of identifying stem cells from among the widely varied types of cells found in bone marrow. This is no easy task, as only one out of 100,000 cells is a stem cell. After it recognizes the right cells, the chip has to sort and channel them to a culture dish where they can reach the critical mass point for tissue engineering.
“The next challenge is to identify the conditions whereby a stem cell will turn into each type of required tissue,” says Benayahu. “The nano-biotechnological tools we design will have to mimic natural processes of cellular signaling and differentiation.”
Benayahu points out the multidisciplinary nature of the project. Biologists are investigating different types of cells and cellular mechanisms; engineers are designing the chips; and physicists and chemists are working on the interface between biology and nano-mechanics. Every three months the research teams meet for a day-long symposium to share their findings, and occasionally one or a few partners will hold a smaller gathering.
“By the end of the project we hope to build a prototype of the tissue machine, or at least parts of it,” says Benayahu. “There is tremendous interest by the biomedical industry in this technology, which could improve the quality of life of hundreds of thousands of patients the world over,” she says.
In addition to its participation in CellPROM, Tel Aviv University is the only Israeli institution affiliated with another major pan-Europe initiative – the Nano2Life European Network of Excellence in Nanobiotechnology. The driving force behind TAU’s joining the network were Prof. Shacham; Dr. Yair Sharan, Director of the Interdisciplinary Center for Technological Analysis and Forecasting (ICTAF); and Dr. Ron Maron, Managing Director of the Institute for Nanoscience and Nanotechnology.
A four-year project, Nano2Life provides a framework for collaborative thinking among 200 researchers from 23 institutions in the fields of biology, medicine and nanotechnology.
“The main objective of Nano2Life is to promote research and applications in the hottest nanobiotech fields, such as sensing devices, drug delivery and fabrication of new materials like nanowires,” says Prof. Rafi Korenstein, a biophysicist at the Sackler Faculty of Medicine, the head of the Marion Gertner Institute for Medical Nanosystems, and the coordinator of TAU activity in Nano2Life.
“TAU has recognized strengths in these fields,” says Korenstein. “We’re a major partner in the network in terms of both the scope and quality of the research we’re initiating.”
Out of 10 strategic research areas identified by Nano2Life, three are led by TAU faculty members. Korenstein heads nano-based drug delivery; Prof. Ehud Gazit of the Department of Molecular Microbiology and Biotechnology, Wise Faculty of Life Sciences, heads the nanoscale assemblies group; and Dr. Mira Marcus-Kalish, Senior Researcher at ICTAF, leads the converging technologies group. Other research topics range from nano-imaging and improvement of biochips to nanotechnology and cancer.
Dr. Marcus-Kalish also coordinates the joint research activities of the entire Nano2Life network. This includes determining the focus of the 10 research areas, arranging for exchanges between students and faculty members, bringing scientists together for meetings and for writing joint grant proposals, and enabling researchers to gain access to facilities and equipment. Two gatherings have been held on the TAU campus, and the network’s one-year anniversary conference was held recently in Germany.
“We’re hoping to evolve into a permanent European Institute of Nanobiotechnology,” notes Marcus-Kalish. Along with overseeing research, this body would also tackle ethics and regulatory issues, conduct short and long-term health risk assessments, and manage technology transfer. Nano2Life is already working closely with more than 20 industrial partners to develop new nanobiotechnological instruments and materials for health care, the environment, security, and food safety.
A specialist in biological modeling, Marcus-Kalish is enthusiastic about the possibilities inherent in the nano-bio interface. “Nano is the language of the body. If you want to speak this language, you have to work on the nano scale,” she says.
In the converging technologies area, which Marcus-Kalish leads, nanotechnology experts and engineers are working with biologists, medical doctors and cognitive science specialists to provide all-encompassing, holistic solutions for treating diseases or enhancing the physical and mental capabilities of the human body.
“More than describing any specific product or process, the term ‘converging technologies’ represents a call to action,” says Marcus-Kalish. “The new trend in the scientific world is to see a person – body, psychology and cognition – as inextricably connected to environment and society as a whole. If you want to solve a problem, you need to address every angle of it simultaneously, and to find new ways of integrating and exploiting existing and new knowledge,” she says.
“For example, when designing a drug, you need to take into account the patient’s individual biology, state of mind, eating habits, and environmental and cultural context,” Marcus-Kalish says.
Korenstein believes that “nano is the last visible frontier of science – miniaturization on the atomic and molecular level.”
“If you can implant a nano device in the body and operate it, you may be able to repair single cells or parts of cells,” he says. Likewise, new materials fabricated on the nano scale could be more reliable, stronger and of multiple uses.
Korenstein would like to recruit more scientists across the campus to interdisciplinary research activity in nanoscience and nanotechnology, “but we need more resources,” he says. “We’ve got the people with the talent, imagination and multidisciplinary approach – TAU has tremendous nano potential.”