Dr. Yosef Buganim, a research scientist at the Hebrew University of Jerusalem, has been honored by the American Association for the Advancement of Science (AAAS), the prestigious journals Science and Science Translational Medicine, and the Boyalife industrial research consortium, for his work in stem cells and regenerative medicine (see Dr. Buganim’s essay Back to basics).
Dr. Buganim is a young researcher who recently joined the Department of Molecular Biology and Cancer Research at the Institute for Medical Research Israel-Canada (IMRIC). Part of the Hebrew University’s Faculty of Medicine, IMRIC is one of the most innovative and multidisciplinary biomedical research organizations in the world.
Awarded for the first time this year, the Boyalife Science & Science Translational Medicine Award in Stem Cells & Regenerative Medicine honors researchers for outstanding contributions in stem cell research and regenerative medicine around the globe. AAAS, Science, and Science Translational Medicine joined efforts with Boyalife, an industrial-research consortium formed in Wuxi, China, in 2009, to sponsor the award. Composed of prominent researchers, the judging panel was co-chaired by a Science and a Science Translational Medicine editor.
At his Hebrew University laboratory, Buganim uses somatic cell conversion models to identify and investigate the elements that facilitate safe and complete nuclear reprogramming. As a postdoctoral fellow at the Whitehead Institute for Biomedical Research at MIT, he used single-cell technologies and bioinformatic approaches to shed light on the molecular mechanisms that underlie the reprogramming of somatic cells to iPSCs.
Regenerative medicine is a developing field aimed at regenerating, replacing or engineering human cells, tissues or organs, to establish or restore normal function. Embryonic stem cells have enormous potential in this area because they can differentiate into all cell types in the human body. However, two significant obstacles prevent their immediate use in medicine: ethical issues related to terminating human embryos, and rejection of foreign cells by a patient’s immune system.
In 2006, Japanese researchers discovered that it is possible to reprogram adult cells and return them to their embryonic stage, creating functional embryonic stem-like cells. These cells are known as induced pluripotent stem cells (iPSCs), and constitute a solution to these two obstacles. In addition, these cells provide a good basis for modeling diseases and finding medical solutions, because they can be reproduced from different patients and different diseases.
Despite these cells’ enormous potential, their quality is still not sufficient to be used in clinical practice, and there is a need to find the best protocol that will enable production of high-quality iPSCs that will not endanger patients.
Dr. Buganim’s laboratory has made two major breakthroughs in this area, representing a major step forward in the field of regenerative medicine and transplantation.
Project A: To improve the quality of embryonic stem cells, Dr. Buganim and colleagues conducted bioinformatics analyses which pointed to four new key genes capable of creating iPSCs from skin cells, of superior quality to stem cells in current use. These cells produced in his laboratory (in this case mouse cells) are able to clone a whole mouse at a much higher percentage (80%) than other iPSCs (30%). This test is the most important one determine the quality of the cells.
Project B: Many women suffer recurrent miscarriages and abnormal development of the placenta, which causes fetal growth restriction and in some cases produces children with mental retardation. Dr. Buganim’s lab found the key genes of the placenta stem cells and by expressing them in surplus in skin cells, created placental iPSCs. These cells looked and behaved like natural placental stem cells. Various tests showed that these cells have cell-generating capability in a Petri dish and inside a placenta that develops following a transplant. These cells have potential for use in regenerative medicine in cases of problematic placental functioning. The success of this project may enable women with placenta problems to give birth to healthy children and rescue pregnancies at risk of dysfunctional placenta (see Scientists Convert Skin Cells Into Functional Placenta-Generating Cells).
Alongside creating specific cell types (e.g. nerve cells in patients with Parkinson’s disease, ALS and Alzheimer) from a patient’s skin cells, a potential future use of iPSCs is the creation of whole organs (such as heart, liver or kidney) in a suitable animal model using cells taken from the patient.