In July's Nature Review, six leading stem cell researchers discussed the state of current research and challenges in developing and applying therapeutic applications using human stem cell technology. The researchers from leading institutes worldwide shared many similar views regarding the value of engineered stem cells as compared with those derived from embryos, and the potential of treatments that reprogram cells in the body versus growing replacement in the lab. Here's an overview of some of their perspectives.
Induced Pluripotent Cells v. Embryonic Stem Cells
There are differences between embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells) from different sources, but the researchers did not see any significant consistent differences between the two types of stem cells. They were of the opinion that iPS cells were essentially equivalent to stem cells isolated directly from embryos.
As Dr. George Daley, the Director of Stem Cell Transplantation Program at Children's Hospital Boston, stated, "iPS cells are virtually indistinguishable from ES cells by functional and molecular criteria." Dr. Cedric Blanplain, a researcher at the Universite Libre de Bruxelles that studies stem cell development and cancer voiced the belief that, "it is very likely that iPS cells will replace human ES cells for most applications."
To emphasize the equivalence, Dr. Konrad Hochedlinger, from Harvard's Department for Stem Cell and Regenerative Biology noted that, "certain mouse iPS cells can be used to make a whole mouse, so they pass the strictest developmental assay." However, of course, human iPS cells have not been evaluated in such a way. He felt there still may be some differences between the two types of stem cells yet to be discovered.
While believing the two cells types to be virtually equivalent, the panel all agreed that much more research needed to be done with embryo-derived stem cells. These cells are necessary to build a strong enough understanding of the differentiation process to be able to tell if iPS cells are really interchangeable with ES cells in all circumstances.
Transdifferentiation v. Regneration
The process of cultivating stem cells in the lab so that they grow into fully differentiated functional cells involves a lot of work. For medical purposes, it may be much more practical to "reprogram" already differentiated cells right in the body. This reprogramming process to turn one type of body cells into another, for example inducing skin cells to become nerve cells, is called trandifferentiation. While most of the researchers felt this approach had real practical benefits for many therapeutic applications, the biggest obstacle is the lack of understanding of how to do it.
As Dr. Daley put it, "transdifferentiated cells remain rather poorly characterized and not well understood." Dr. Hochedlinger agreed that, we still have a poor understanding of the type of cells actually generated by transdifferentiation. This is maybe not surprising. Much of the research is still attempting to dissect the process of going from stem cells to various mature body cells.
It would seem necessary to first understand the many variations of this differentiation process to make all the body's cells before researchers could understand how one type of cell might be turned into another. As Dr. Blanplain put it, "a much better understanding of how stem cells are normally activated during endogeneous tissue repair is a prerequisite" to reactivating body cells to mediate tissue repair.
Biggest Hurdles in Developing Stem Cell Treatments
All the researchers agreed there needs to be a better understanding of the process of differentiation and the specific conditions to grow, maintain, and differentiate stem cells in laboratory cultures. According to Dr. Shinya Yamanaka, the first researcher to make iPS cells expressed that, "techniques need to be developed to differentiate and culture ES and iPS cells into several lineages, such as hematopoietic progenitor cells,and insulin producing cells" Dr. Hochedlinger noted that they have not even been able to get reliable conditions to preserve and maintain multipotent blood progenitor cells in the lab. They have been working with these adult stem cells for more than 30 years.
Dr. Blanplain pointed out that, "at this point, there are major technical hindrances to proper differentiation of stem cells into mature and functional cells that can be engrafted and functional integrated into damaged tissues."
It was clear that there is still not enough practical understanding of the how to handle and culture undifferentiated human stem cells in the laboratory. The tools to manipulate and control the conditions of differentiation are needed to gain a deeper understanding of the details of the differentiation process of both research and therapeutic applications.
See the complete article in Nature Reviews for the discussion in its entirety: Nature Reviews Molecular Cell Biology 13, 471-476 (July 2012). Also, for background information on stem cell technology, you might also take a look at "The Range of Stem Cell Technology."