Previously undetected human hematopoietic cell populations with short-term repopulating activity selectively engraft NOD/SCID-β2 microglobulin–null mice

Indian hedgehog gene transfer augments hematopoietic support of human stromal cells including NOD/SCID–ß2m–/– repopulating cells.

“…It was demonstrated by Glimm et al 35 that NOD/SCID-ß 2 m Ϫ/Ϫ mice are sequentially engrafted by 2 distinct populations of transplantable human short-term repopulating hematopoietic cells (STRCs) in addition to long-term repopulating hematopoietic cells (LTRCs), which equivalently engraft either NOD/SCID mice or NOD/SCID-ß 2 m Ϫ/Ϫ mice. One of these populations is myeloidrestricted STRC (STRC-M), which produces the large and rapid but transient burst of erythroid dominant cells seen in the first 3 weeks after transplantation.…”

“…It was shown that STRCs are markedly higher in mobilized peripheral blood as compared with BM and CB, and this elevated STRC content of mobilized peripheral blood could explain the apparently faster rates of hematologic recovery that they typically achieve clinically. 35,36 Therefore, coculture with Ihh stromal cells and CB leads to expansion of STRCs, and this could compensate for delayed recovery of myelo-suppression after CB transplantation. 3 Further study using larger animal models will be required to elucidate whether the expanded STRCs actually contribute to early reconstitution of the BM.…”

Relatively Normal Human Lymphopoiesis but Rapid Turnover of Newly Formed B Cells in Transplanted Nonobese Diabetic/SCID Mice

“…However, this is the first detailed investigation of all stages of B lymphopoiesis with a direct comparison to the replication and differentiation events that occur within normal marrow. Stem cells with long-term repopulating potential are thought to be nonreplicating and part of the CD34 ϩ CD38 Ϫ fractions of human marrow or cord blood (7,10,48). Furthermore, this nonproliferating fraction contains the SCID mouse repopulating cells (49,50).…”

Insights into the stem cells of chronic myeloid leukemia

“…A second reason is the fact that adequately immunodeficient long-lived mice to serve as suitable hosts have only recently become available. Both sub-lethally irradiated SCID and NOD/SCID mice retain sufficient endogenous natural killer cell activity to eliminate injected human short-term repopulating cells even though those with long-term activity may survive 53 and it may be that chronic phase CML cells have a generalized heightened sensitivity to natural killer activity compromising further their ability to perform in these mice. Thus, although a substantial leukemic population can be readily regenerated from transplanted blast crisis CML patients' cells, this is not true with chronic phase CML cell transplants.…”