Adult testicles could one day become a common source for stem cells to cultivate a host of tissue types to combat disease, while at the same time avoiding the ethical resistance to embryonic stem cells, say researchers from Weill Cornell Medical College, New York City, USA. You can read about this latest research in the journal Nature, September 20 issue.
Using SPCs (spermatogonial progenitor stem cells) which came from the testes of mice, the scientists were able to tweak them in the lab to form MASCs (multi-potent adult spermatogonial-derived stem cells). These cells were developed into endothelial (working blood vessel) cells and tissue, cardiac cells, brain cells and a range of other cell types.
Previous research had managed to reprogram genetically manipulated adult cells derived from connective tissue to become potential stem cells. However, this method, known as induced pluripotency, increased the risk of transforming some of these cells into malignant ones, the writers explain.
Team leader, Dr. Shahin Rafii, explained “What’s really novel about our work is that – unlike induced pluripotency – these mouse SPCs do not require any addition or tweaking of genes to get them to form the multi-potent cells (MASCs) that then go on to produce all of these cell types. Some hurdles remain, of course – we have to replicate these findings in humans, and we haven’t discovered the exact ‘switch’ that would allow us to control SPC development on demand. Nevertheless, it appears that these unique specialized spermatogonial cells could be an easily obtained and manipulated source of stem cells with exactly the same capability to form new tissues that we see in embryonic stem cells.”
SPCs, which are located in the testicles, have one function – to make the precursors to sperm.
Lead author, Dr. Marco Seandel, wrote “Normally, the spermatogonial progenitor cell is committed to only that function, and they’re remarkably efficient, keeping men fertile well into advanced age.” Dr. Seandel is a researcher at the Howard Hughes Medical Institute and provided the first real breakthrough in this research – he developed the first effective/efficient way of growing lots of SPCs for experimental laboratory use.
Dr. Rafii says that that really allowed them to go full steam ahead in exploring the potential of these fascinating cells.
In this study, the team created the ideal in vitro biochemical environment for the SPCs, involving particular helper cell types and growth factors designed to foster SPCs development away from creating germ cells and toward the ability to turn into varying types of cells (multipotency).
“One problem,” explained Dr. Seandel “with working with SPCs is that they’ve been extremely difficult to identify. We discovered that, within the testicular environment, only SPCs express a particular marker called GPR125. That’s a quantum leap forward in terms of being able to harvest and work with these cells.”
After being left for some time in their special environment, the SPCs eventually turned into what the team had been hoping for. Rather than turning into germ cells they developed into MASCs (spermatogonial-derived stem cells).
In mouse-tissue and in vitro studies the MASCs turned into a full range of cell types.
Co-author and investigator, Dr. Daylon James, who works in Dr. Raffia’s lab, said “We took them furthest when it came to endothelial cells. In experiments in live mouse tissue, we were able to show that these MASC-derived endothelial cells did more than just form – they also joined up with, and functioned alongside, other blood vessels.”
MASCs also produced cardiac cells, muscle cells, and neurons in the lab.
In order to be able to create MASCs on a routine bases, Dr. Seandel says it will be necessary to fully understand the exact biochemical and genetic switch that instructs the cells to become MASCs – they do not fully understand that yet.
Team member, Dr. Pier Paolo Pandolfi, Harvard Medical School, said “The other hurdle is to repeat this success in human cells, by utilizing the same stem-cell markers, including GPR125 and also another specific marker, Plzf.”
Dr. Rafii explained that it could one day mean having a readily available source of stem cells for male patients, without having to go through the ethical gauntlet of embryonic stem cells. Such issues as transplant rejection would be avoided, as these stem cells originate from the patient’s own body.
The female ovary has a large population of germ cells. Could this approach work there? According to the Weill Cornell team it might.
Dr. Rafii added “Our achievement using these testes-derived cells has taken us over a decade of painstaking investigation to achieve. It points to the potential of this remarkable, but – until now – poorly accessed and understood stem cell. We hope this seminal paper will set the stage for designing clinical strategies for regenerating failing organs in patients with heart disease, Alzheimer’s, Parkinson’s, stroke, diabetes, arthritis, macular degeneration and infertility induced by chemotherapy and irradiation. Delivering stem cells derived from MASCs, loaded with toxic factors, to the tumor microenvironment may also provide a novel strategy to target tumor blood vessels and inhibit cancer growth and metastasis.”
— http://www.med.cornell.edu
— http://www.nature.com
Written by: Christian Nordqvist