Friday March 9 2012
Stem cells may stop the body from rejecting a donor kidney (red)
“Stem cells beat kidney rejection,” says BBC News. The broadcaster says that an injection of stem cells given alongside a kidney transplant could remove the need for a lifetime of treatment to suppress the immune system.
The news is based on research detailing the outcomes of eight experimental kidney transplants where the organ came from a living donor. In addition to having their kidney removed, the donor also donated blood stem cells, which can develop into any type of blood cell, including immune system cells. After the recipient patient had received chemotherapy and radiotherapy to suppress their own immune system, the donor kidney and stem cells were transplanted. The aim was to help prevent the organ from being rejected by altering the recipient’s immune system to match that of the donor kidney. Five of the eight patients were able to have their immunosuppressant drugs reduced within one year. Furthermore, there was no evidence that the donor’s transplanted immune cells had started to attack the recipient’s healthy tissue, a possible complication of this type of treatment.
Although this is only early-stage research, the results of this small case series are promising and could have implications for the future of organ transplants, particularly in those cases where the donor and recipient are not matched to each other.
Where did the story come from?
The study was carried out by researchers from Comprehensive Transplant Center, Northwestern Memorial Hospital, Chicago and other institutions in the US. Funding was provided by the US National Institute of Health; the Department of the Army, Office of Army Research; the National Foundation to Support Cell Transplant Research; the WM Keck Foundation; and the American Society of Transplant Surgeons Collaborative Scientist Award. The study was published in the peer-reviewed journal Science Translational Medicine.
The BBC News website provides good coverage of this research.
What kind of research was this?
This was a case series reporting on the results of eight patients receiving kidney transplants alongside haematopoietic stem cells (HSCs – cells that can develop into any type of blood cell). These were taken from “mismatched” donors (either related or unrelated to the recipient). If they are “mismatched”, the donor and recipient do not share the same human leukocyte antigens (HLAs), which are proteins located on the surface of immune cells and other cells in the body. The immune system recognises “foreign” HLAs and will attack cells that carry them, potentially leading to rejection. If donor cells carry the same HLAs there is less chance that the host’s immune cells would recognise the transplant tissue as foreign. This is why the ideal situation is to find a suitable HLA-matched donor for individuals awaiting a transplant, although this is often not possible.
This research investigated a theory known as “chimerism” (named after a mythical creature made up of parts of different animals), where the transplant recipient has both their own immune cells and those that come from the donor. The hope is that this will prevent the body from rejecting the transplant. However, there is a chance that this could increase the risk of what is known as graft versus host disease (GVHD), which is where the donor’s immune cells instead attack the healthy tissue of the host. HSC transplant also carries a risk of what is known as “engraftment syndrome”, which is characterised by a fever, skin rash and other symptoms.
What did the research involve?
This case series reported the outcomes of eight adults (age range 29-56 years) who were receiving a kidney transplant from a living, unmatched donor. A special technique was used to retrieve relevant cells from the donor’s blood, including both HSCs and “graft facilitating cells” (FCs – which are a type of immune cell derived from HSCs).
Prior to transplant of the donor kidney and HSCs/FCs, the recipients were first treated with chemotherapy and radiotherapy to suppress their own immune system and reduce the chance of rejection. After the transplant they received continued treatment with two drugs to suppress their immune system and reduce the chance that their bodies would reject the transplant. They were discharged from hospital two days after the transplant and managed as outpatients.
The researchers monitored the patients to look at how the procedure was tolerated and whether GVHD or engraftment syndrome occurred.
What were the basic results?
By one month after transplant the level of chimerism in the recipients’ blood (where they demonstrated cell lines coming from both their own stem cells and the donor’s stem cells) was reported to vary between 6 and 100%.
One patient developed a viral blood infection and blood clot in one of their kidney arteries two months after transplant. Two patients demonstrated only slight chimerism and were maintained on low-dose immunosuppressive treatment. However, five patients demonstrated “durable chimerism” and were able to be weaned from immunosuppressive treatment by one year. None of the recipients developed GVHD or engraftment syndrome.
How did the researchers interpret the results?
The researchers conclude that transplant of HSCs is a “safe, practical, and reproducible means of inducing durable chimerism”. It also appeared to be tolerated with no signs of GVHD or engraftment syndrome.
If confirmed in larger studies, the researchers say that this approach to transplantation could free some patients from the need for immunosuppressive treatment within one year of transplantation.
This research reported on the cases of eight patients who were receiving a kidney from an unmatched living donor. Alongside the kidney transplant, recipients were also given a transplant of the donor’s haematopoietic stem cells, which have the ability to transform into a range of blood cell types. The aim was that slightly altering the recipient’s immune system to produce cells that “matched” those of the donor kidney would help prevent the organ from being rejected. Five of the eight patients were able to have their immunosuppressant drugs reduced within one year. Furthermore, no patients developed a serious condition called graft versus host disease (where the donor’s transplanted immune cells start to attack the recipient’s healthy tissue), and no patients developed another complication of HSC transplant, known as engraftment syndrome, which includes fever, skin rash and other symptoms.
Importantly, this is only early-stage research, reporting the results of treatment in only eight people. Further follow-up in these patients will be needed, in addition to study in much wider groups of patients. However, the results are promising and could have implications for the future of kidney transplant and the transplant of other organs, particularly in people for whom it has not been possible to find a suitable matched donor.
Analysis by Bazian