Hemopoietic stem cells: Analysis of some parameters critical for engraftment

Abstract

In this review four parameters relevant to the grafting of hemopoietic stem cells (HSC) are analyzed: the nature and amounts of grafted HSC, the sources of HSC and the "in vivo" fate of the grafted cells. One may oppose cells with short-term repopulating ability to cells with long-term reconstitutive capacity. The former comprise progenitors, while the latter consist of primitive stem cells, corresponding to murine pre-colony forming units-spleen (pre-CFU-S) (and to some murine CFU-S) or to human pre-colony forming units (pre-CFU). In the mouse, the number of progenitors involved in short-term reconstitution is large, while that of primitive cells operating months after the transplantation is reduced. These results may be extrapolated to humans, suggesting that it is possible to engraft a limited number of genetically modified HSC. However, the administration of large numbers of reconstituting cells appears to be a cautionary procedure, since it should insure polyclonal hemopoiesis, which is the physiological situation in mammals. Besides marrow, peripheral blood from adult patients treated with chemotherapy and growth factors, and cord blood from newborns, are promising sources of HSC. Successful engraftment depends not only on the quality and quantity of HSC, but also on the integrity of the marrow microenvironment. This microenvironment may be impaired by chemo- and radiotherapy, which provides a theoretical basis for the transplantation of stromal cells along with that of HSC.

Bone Marrow as Multidimensional Orbit Oscillator after Autologous Bone Marrow Transplantation

“…This hypothesis supports the finding that the administration of large numbers of reconstituting cells that represent heterogeneous populations appears to be a cautionary procedure, since it should ensure polyclonal hemopoiesis after bone marrow transplantation (BMT) [10]. The cyclic processes of cell proliferation and differentiation are both stochastic on one or few cell levels and controlled on compartment and organ levels [11].…”

Potency, Proliferation and Engraftment Potential of Stem Cell Therapeutics: The Relationship between Potency and Clinical Outcome for Hematopoietic Stem Cell Products

“…Mature stem cells would be expected to exhibit a lower potency than primitive stem cells and therefore a lower engraftment potential. From a practical viewpoint this means that mature stem cells would be expected to demonstrate short-term engraftment [22][23][24][25] and reconstitution while more primitive stem cell would demonstrate long-term engraftment and reconstitution [22,25,26]. As a result, measuring the potency of just a single stem cell population, especially a mature stem cell population, could result in a false interpretation and conclusion.…”

Proliferation kinetics of subpopulations of human marrow cells determined by quantifying in vivo incorporation of [2H2]-glucose into DNA of S-phase cells

“…In vivo labeling kinetics during 2 [H]-glucose infusion were determined for CD41a (megakaryocyte lineage) and for glycophorin A (erythroid lineage)-expressing cells remaining in marrow samples after CD34 ϩ cell selection. Glycophorin A ϩ cells had a mean t 1/2labeling of 3.5 days (range, 2-6 days) ( Table 5).…”

“…Subpopulations of hematopoietic progenitors not only differ in their selfrenewal, proliferation, and differentiation capacities, [1][2][3][4][5] but they also have different cell cycle and turnover kinetics. [1][2][3][6][7][8] For example, in vivo bromodeoxyuridine (BrdU)-labeling studies demonstrated that murine marrow primitive progenitors capable of long-term reconstitution of lethally irradiated mice have turnover times of 30 days or longer. 6,7 In contrast, granulocyte/macrophage committed progenitors have rapid turnover times of only 1 to 2 days.…”