Reviews: The origins of the identification and isolation of hematopoietic stem cells by Irving Weissman

by Alexey Bersenev on November 6, 2008 · 1 comment

in reviews

ASH 50th anniversary review written by Irving Weissman and Judith Shizuru. You can find a lot of historical aspects of hematopoietic stem cells (HSCs) identification and isolation.

HSCs were defined as single cells with lifelong ability to self-renew as well as differentiate to produce all blood cell lineages (multipotency). Any discovery of HSCs or populations of cells enriched for HSCs should show full multipotency as well as self-renewal.

I was happy to find an excellent picture, combined hematopoietic hierarchy scheme with surface markers of progenitors for mouse and human:

weissman.jpg(click to enlarge)

The second part of review described clinical uses of HSCs isolation for cancer patients, tolerance induction and autoimmune diseases treatment.

What might be the value of prospective isolation of HSCs for human therapies? In studies of experimental hematopoietic cell transplantation (HCT) and clinical HCT, grafts contain heterogeneous populations of HSCs as well as downstream progenitors and mature blood cells. For patients with certain hematologic or advanced-stage malignancies who undergo autologous HCT, their grafts can additionally contain contaminating cancer cells. For this latter group of patients, prospectively isolated HSCs could serve as a tumor free graft that would rescue patients from supralethal doses of chemotherapy/radiation.

future directions:

The technologies of selection and sorting will allow the cellular “engineering” of hematopoietic grafts of defined cell types. HSCs that are free of cancer can form the foundation for autologous and allogeneic grafts aimed at rescuing patients from the unwanted effect of high-dose radiation and chemotherapy. Immune populations with specific antitumor activity can be incorporated into the grafts to capitalize on the cellular therapeutic effects.

The treatment of a host of nonmalignant diseases by haplo-identical and HLA-mismatched HSCs awaits the advent of new conditioning regimens wherein the host is not in danger from the conditioning, yet pure HSCs, incapable of any GVHD, can engraft sufficiently to reverse the genetic or acquired blood cell disease.

Finally, we envision that infectious diseases of the blood system, such as AIDS, tuberculosis, malaria, and leprosy, might be treated with autologous gene-modified HSCs to produce T cells, red blood cells, and macrophages that resist colonization by the infectious agent.

at the end he is highlight concerns about nomenclature confusions:

A very strange phenomenon concerning nomenclature has evolved in clinical hematopoietic cell transplantation. Papers in the early mid-1990s described the transplants by the cells given—bone marrow, mobilized peripheral blood, and so on—whereas sometime thereafter all transplants became “stem cell transplants,” regardless of the type of cells used. This weakening of the appropriate designation of the transplant has consequences, as clinicians not familiar with the difference between unmanipulated marrow or MPB grafts and purified or semipurified populations will be impaired in their ability to know what hematopoietic population was given, and whether cancer cells, T cells, progenitor cells, and so on comprised the transplant.

must read!

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Vlad November 6, 2008 at 1:04 pm



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