Regeneration of splenic stromal elements

Abstract

Splenic regeneration represents an interesting phenomenon both in relation to its role as a model system (to study the development of the complex three-dimensional architecture of an immunological organ) and because of the clinical application, namely autotransplantation of spleen. The latter is one of the attempts to restore splenic functions after splenectomy, which is known to increase a life-long risk of fatal sepsis. However, splenic functions of autotransplanted splenic tissue are known to be highly dependent on the recovery of the complex microenvironment and immunoarchitecture of the splenic compartments during the regeneration processes, but the elements inducing splenic reorganization are still unknown. Therefore, the present work investigates whether splenic stroma depleted of cells is able to induce regenerative processes after implantation. In addition, we tried to recombine stromal tissue with selected cell populations to study their influence. Cell-free stromal tissue induced angiogenesis and to a lesser extent also attracted the immigration of lymphocytes during the first 60 days of regeneration. However, after this period of regeneration, the transplants began to degenerate and were resorbed. The recombination of stromal tissue with mitogen-stimulated spleen cells only resulted in intensifying the degenerative processes, and all implants were resorbed after 120 days. Except that in the first 30 days there were some accumulations of lymphocytes that resembled primitive follicles, no splenic compartments such as red pulp, periarteriolar lymphoid sheath, or marginal zone could be detected in any of the transplants. From these results it can be concluded that splenic stroma can induce the primary events of splenic regeneration (like angiogenesis), but is not able to provide an appropriate microenvironment and immunoarchitecture for a correct repopulation and differentiation of cells. Furthermore, the recombination experiments point to a minor role of T-cells and possibly an important role for accessory cells in splenic regeneration.