Blood cells are responsible for constant maintenance and immune protection of every cell type of the body. This demanding work requires that blood cells, along with skin cells, have the greatest powers of self-renewal of any adult tissue. The stem cells that form blood and immune cells are known as hematopoietic stem cells (HSCs). They are ultimately responsible for the constant renewal of blood—the production of billions of new blood cells each day. Physicians and basic researchers have known and capitalized on this fact for more than 50 years in treating many diseases. The first evidence and definition of blood-forming stem cells came from studies of people exposed to lethal doses of radiation in 1945. Basic research soon followed. After duplicating radiation sickness in mice, scientists found they could rescue the mice from death with bone marrow transplants from healthy donor animals. In the early 1960s, Till and McCulloch began analyzing the bone marrow to find out which components were responsible for regenerating blood. They defined what remain the two hallmarks of an HSC: it can renew itself and it can produce cells that give rise to all the different types of blood cells.
What Is a Hematopoietic Stem Cell?
A hematopoietic stem cell is a cell isolated from the blood or bone marrow that can renew itself, can differentiate to a variety of specialized cells, can mobilize out of the bone marrow into circulating blood, and can undergo programmed cell death, called apoptosis—a process by which cells that are detrimental or unneeded self-destruct.
What Are the Sources of Hematopoietic Stem Cells?
The classic source of hematopoietic stem cells (HSCs) is bone marrow. For more than 40 years, doctors performed bone marrow transplants by anesthetizing the stem cell donor, puncturing a bone—typically a hipbone—and drawing out the bone marrow cells with a syringe. About 1 in every 100,000 cells in the marrow is a long-term, blood-forming stem cell; other cells present include stromal cells, stromal stem cells, blood progenitor cells, and mature and maturing white and red blood cells.
As a source of HSCs for medical treatments, bone marrow retrieval directly from bone is quickly fading into history. For clinical transplantation of human HSCs, doctors now prefer to harvest donor cells from peripheral, circulating blood. It has been known for decades that a small number of stem and progenitor cells circulate in the bloodstream, but in the past 10 years, researchers have found that they can coax the cells to migrate from marrow to blood in greater numbers by injecting the donor with a cytokine, such as granulocyte-colony stimulating factor (GCSF). The donor is injected with GCSF a few days before the cell harvest. To collect the cells, doctors insert an intravenous tube into the donor’s vein and pass his blood through a filtering system that pulls out CD34+ white blood cells and returns the red blood cells to the donor. Of the cells collected, just 5 to 20 percent will be true HSCs. Thus, when medical researchers commonly refer to peripherally harvested “stem cells,” this is something of a misnomer. As is true for bone marrow, the CD34+ cells are a mixture of stem cells, progenitors, and white blood cells of various degrees of maturity.
In the past three years, the majority of autologous (where the donor and recipient are the same person) and allogeneic (where the donor and recipient are different individuals) “bone marrow” transplants have actually been white blood cells drawn from peripheral circulation, not bone marrow. Richard Childs, an intramural investigator at the NIH, says peripheral harvest of cells is easier on the donor—with minimal pain, no anesthesia, and no hospital stay—but also yields better cells for transplants. Childs points to evidence that patients receiving peripherally harvested cells have higher survival rates than bone marrow recipients do. The peripherally harvested cells contain twice as many HSCs as stem cells taken from bone marrow and engraft more quickly. This means patients may recover white blood cells, platelets, and their immune and clotting protection several days faster than they would with a bone marrow graft. Scientists at Stanford report that highly purified, mobilized peripheral cells that have CD34+ and Thy-1+ surface markers engraft swiftly and without complication in breast cancer patients receiving an autologous transplant of the cells after intensive chemotherapy.
Umbilical Cord Blood
In the late 1980s and early 1990s, physicians began to recognize that blood from the human umbilical cord was a rich source of HSCs. This tissue supports the developing fetus during pregnancy, is delivered along with the baby, and, is usually discarded. Since the first successful umbilical cord blood transplants in children with Fanconi anemia, the collection and therapeutic use of these cells has grown quickly. Umbilical cord blood recipients—typically children—have now lived in excess of eight years, relying on the HSCs from an umbilical cord blood transplant.
There is a substantial amount of research being conducted on umbilical cord blood to search for ways to expand the number of HSCs and compare and contrast the biological properties of cord blood with adult bone marrow stem cells. There have been suggestions that umbilical cord blood contains stem cells that have the capability of developing cells of multiple germ layers (multipotent) or even all germ layers, e.g., endoderm, ectoderm, and mesoderm (pluripotent). To date, there is no published scientific evidence to support this claim. While umbilical cord blood represents a valuable resource for HSCs, research data have not conclusively shown qualitative differences in the differentiated cells produced between this source of HSCs and peripheral blood and bone marrow.
Source: NIH 2011