Stem Cell Transplant Quotes

The cure for HIV?” “In 2007, a man named Timothy Ray Brown, known later as the Berlin patient, was cured of HIV. Brown was diagnosed with acute myeloid leukemia. His HIV-positive status complicated his treatment. During chemotherapy, he battled sepsis, and his physicians had to explore less traditional approaches. His hematologist, Dr. Gero Hutter, decided on a stem cell therapy: a full bone marrow transplant. Hutter actually passed over the matched bone marrow donor for a donor with a specific genetic mutation: CCR5-Delta 32. CCR5-Delta 32 makes cells immune to HIV.” “Incredible.” “Yes. At first, we thought the Delta 32 mutation must have arisen during the Black Death in Europe—about four to sixteen percent of Europeans have at least one copy. But we’ve traced it back further. We thought perhaps smallpox, but we’ve found Bronze Age DNA samples that carry it. The mutation’s origins are a mystery, but one thing is certain: the bone marrow transplant with CCR5-Delta 32 cured both Brown’s leukemia and HIV. After the transplant, he stopped taking his antiretrovirals and has never again tested positive for HIV.

Similar things happen in so many diseases – the insulin-secreting cells that are lost when teenagers develop type 1 diabetes, the brain cells that are lost in Alzheimer’s disease, the cartilage producing cells that disappear during osteoarthritis – the list goes on and on. It would be great if we could replace these with new cells, identical to our own. This way we wouldn’t have to deal with all the rejection issues that make organ transplants such a challenge, or with the lack of availability of donors. Using stem cells in this way is referred to as therapeutic cloning; creating cells identical to a specific individual in order to treat a disease.

Haematopoietic stem cell transplantation is not a term that is immediately recognizable to the general public but it is actually the same as the much more familiar ‘bone marrow transplantation’. The rather long phrase haematopoietic stem cell transplantation (HSCT) is now preferred because it covers not just transplantation of bone marrow itself but other types of transplant where the blood-forming (haematopoietic) stem cells of the graft come from non-marrow sources such as peripheral blood or umbilical cord blood. Worldwide, about 50,000 HSCTs are carried out each year making this overwhelmingly the most important type of stem cell therapy in current practice. Most are done for treatment of cancer, mainly lymphomas and leukaemias, with about 5 per cent for treatment of non-malignant blood diseases and a few other conditions.

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The obvious solution is stem cells and, while they’re not ready for the clinic yet, “thymus organoids”—small, artificial thymuses grown in the lab—have been shown to work when transplanted into mice without thymuses, and rapid progress is being made in generating thymuses from iPSCs, too.

The study of stem cell niches in mammalian systems presents an 'arduous endeavor'; in comparison, the fly germarium is relatively easy to manipulate. In the 1990s, H. Lin, A.C. Spradling, and others used of a number of approaches to study Drosophilia GSCs and their niche, including killing specific cells in the germarium with precisely directed lasers; transplantation of cells from the ovary of one fly to another; and genetic perturbations that included the dialing up or down of Hh pathway signaling. The researchers found that following laser ablation of cells surrounding the GSCs - that is killing the niche cells - all the GSCs went on to form eggs, and the system was quickly depleted of its GSC reserve. Moreover, through genetic analyses the researchers identified specific genes required in the niche cells to maintain GSCs within the niche, as would be deduced for a gene that, when disrupted in niche cells, has the same effect as laser ablation of those cells. These studies are credited with providing the first clear experimental evidence of a stem cell niche, as well as defining what genes - what signaling pathways and other cellular activities - are important to the process. Many of the same pathways relevant in other cell types proved relevant to communication between the niche and GSCs, including the Hh pathway. The genes required for suppression of transposon mobilization by the piRNA system also have relevance to the GSC niche; disruption of the piwi gene, for example, can lead to uncontrolled proliferation of GSCs.