The infusion of human fetal liver cells

Abstract

Only transient engraftment of infused fetal liver cells has been demonstrated in a small proportion of patients with hypoplastic bone marrow or patients undergoing treatment for acute leukemia. This presumably reflects the ability of the recipient to reject the infused cells, the infusion of too few viable stem cells or the availability of too few accessory cells; it is clear from the successful engraftment of infused fetal liver cells in a high proportion of infants and fetuses with severe immunodeficiency diseases that, under favorable circumstances, cells derived from human fetal liver are capable of establishing effective grafts and making a substantial contribution to hematopoiesis comparable to that of transplanted cells derived from the liver of the fetal mouse, rat, rabbit or dog. Significant clinical and hematological improvements have been described following infusions of fetal liver cells without evidence of engraftment. These improvements have been attributed to the ability of the infused cells to promote regeneration of autologous hematopoiesis and to inhibit the growth of tumor cells. These possibilities are worthy of evaluation in relation to the production of putative regulators of cellular proliferation in the liver. Meanwhile a suppressor of tumor growth is being used to purge bone marrow prior to autologous transplantation. The generation in vitro of cells which possess the properties of hematopoietic stem cells generated in the liver--from cells which can be maintained as permanent cell lines--would transform hematopoietic cell replacement therapy, and the possibility may not be too unrealistic to contemplate.

Stimulation of Adult Human Bone Marrow by Factors Secreted by Fetal Liver Hematopoietic Cells: In Vitro Evaluation Using Semisolid Clonal Assay System

“…Present work was carried out to elucidate the mechanism of autologous recovery observed in some patients treated with FLI therapy, with a special focus on variable responses obtained even in a single clinical group [1][2][3][4][5][6][7][8][9][10][11]. As a first step towards this goal, we carried out experiments to check whether FLHC themselves could stimulate normal adult human BM progenitors, and if they do, then by what mechanism.…”

“…Interestingly, activation of Fas has been reported in CD34 + progenitor cells from aplastic anemia patients [51]. Since the utility of FLI therapy in disorders such as aplastic anemia has been underscored by clinical as well as experimental studies [1][2][3][4][5][6][7][8][9][10][11], it would be important to check whether FLHC treatment and the attendant success in aplastic anemia correlates to the Fas activation profiles on their progenitor cells.…”

“…Fetal liver infusion (FLI) therapy has been attempted in certain major disorders, such as immunodeficiency syndrome, aplastic anemia, leukemia, and genetic or metabolic disorders [1][2][3][4][5][6][7][8][9][10][11]. Although the engrafting capacity of transplanted fetal liver (FL) cells has been successfully demonstrated in animal models [1,12,13], human subjects have shown extremely variable responses to the treatment, ranging from complete recovery on one hand to no response on the other [1][2][3][4][5][6][7][8][9][10][11].…”

“…Although the engrafting capacity of transplanted fetal liver (FL) cells has been successfully demonstrated in animal models [1,12,13], human subjects have shown extremely variable responses to the treatment, ranging from complete recovery on one hand to no response on the other [1][2][3][4][5][6][7][8][9][10][11]. Most of the animal studies, however, are done with complete pretransplant immune suppression, while in the case of human subjects such preconditioning was not followed routinely.…”

Alternative Sources of Hematopoietic Stem Cells for Bone Marrow Transplantation and Rescue

“…It also has been suggested that fetal liver cells may promote the recovery of autologous hematopoiesis and inhibit proliferation of leukemic cells (Thomas, 1993). One retrospective study found a higher rate of complete remission (65%) in patients who received fetal liver cell infusions following treatment for acute myeloid leukemia than in those patients who did not receive fetal liver cells (36%) (Wang, 1992).…”