Targeting the Spleen as an Alternative Site for Hematopoiesis

Bone marrow is the main site for hematopoiesis in adults. It acts as a niche for hematopoietic stem cells (HSC) and contains non-hematopoietic cells that contribute to stem cell dormancy, quiescence, self-renewal and differentiation. HSC also exist in resting spleen of several species, although their contribution to hematopoiesis under steady-state conditions is unknown. Spleen can however can undergo extramedullary hematopoiesis (EMH) triggered by physiological stress or disease. With loss of bone marrow niches on aging and disease, spleen as an alternative tissue site for hematopoiesis is an important consideration for future therapy particularly during HSC transplantation.

In terms of harnessing spleen as a site for hematopoiesis, here we consider the remarkable regenerative capacity of spleen with a view to forming additional or ectopic spleen tissue through cell engraftment. Studies in mice indicate potential for such grafts to support the influx of hematopoietic cells leading to development of normal spleen architecture. An important goal will be the formation of functional ectopic spleen tissue as an aid to hematopoietic recovery following clinical treatments that impact bone marrow. For example, expansion or replacement of niches could be considered where myeloablation ahead of HSC transplantation compromises treatment outcomes.