[PDF][PDF] Requirement of stromal cells in the bone marrow transplant for rapid lymphoid replenishment

S Janczewska, A Ziolkowska, M Durlik… - Transplantation …, 1999 - academia.edu
S Janczewska, A Ziolkowska, M Durlik, E Cybulska, WL Olszewski, B Lukomska
Transplantation proceedings, 1999academia.edu
BONE marrow transplantation (BMT) for treatment of hematologic and solid malignancies is
routinely carried out in conjunction with radio-and chemotherapy. Many patients achieve
complete clinical remission of the malignant process; however, their hematopoietic recovery
remains in most cases incomplete. The frequency and the severity of infections developing
in BMT recipients point to the deficiency of immune functions. The 100-day postgrafting
period of high infection risk is associated with lymphopenia and insufficiency of various T …
BONE marrow transplantation (BMT) for treatment of hematologic and solid malignancies is routinely carried out in conjunction with radio-and chemotherapy. Many patients achieve complete clinical remission of the malignant process; however, their hematopoietic recovery remains in most cases incomplete. The frequency and the severity of infections developing in BMT recipients point to the deficiency of immune functions. The 100-day postgrafting period of high infection risk is associated with lymphopenia and insufficiency of various T-and B-cell functions. Lymphoid cells are derived from pluripotential stem cells; 1 however, little is known about the mechanisms promoting and regulating lymphopoiesis. Successful engraftment with bone marrow cells (BMC) depends on the stromal cells providing mechanical support for hemopoietic cells, and on humoral factors and extracellular matrix molecules sequestering growth factors from the environment. 2–5 The impairment of lymphohemopoietic cell recovery after BMT is probably due to the functional changes in the recipient BM stromal cells subsequent to radio-or chemotherapy. Evaluation of the in vivo function of stromal cells is difficult. Intravenous injection of BMC in suspension (a routine clinical method) provides the recipient with hematopoietic cells deprived of contact with their stromal cells. Transplantation of BM hematopoietic cells in a spatial relationship with stromal cells would offer an insight into the kinetics of hematological restitution of the recipient and recovery of various cell lineages, among them lymphocytes.
To fulfill these requirements, the most appropriate would be a model of vascularized bone marrow transplantation (VBMT). This can be achieved by transplantation of the extremity containing intact BM in bones. Such a graft with preserved lymphohemopoietic activity would resume its function soon after transplantation and almost immediately repopulate bone marrow cavities of the irradiated recipient, as well as supply the sites of cytopoiesis with the necessary growth factors. We reported previously that VBMT brought about complete hemopoietic repopulation of BM cavities in lethally irradiated syngeneic rats within 10 days. 6–9 The question arises as to how effective would the reconstitution of lymphoid organs be after VBMT. In this study we investigated the regenerated population of peripheral blood and lymphoid organs of irradiated rats after VBMT and
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