Hematopoietic stem cells: Can it be a therapeutic option for the hematopoietic failure in patients with trauma-hemorrhagic shock?

Hemorrhagic shock (HS) is the third major cause of death in trauma[1] with a limited therapeutic option. Fluid, blood component, and control of hemorrhage have been the cornerstone of management. Previous studies reported that resuscitation with fluids and blood products induces reperfusion ischemia due to the production of reactive oxygen species and activation of immune cells.[2] Hematopoietic failure and bone marrow (BM) dysfunction have been observed in experimental animals and human following shock and injury.[3,4] Impairment of hematopoietic progenitor cells (HPCs) is clinically associated with persistent anemia and patients are susceptible to infection, sepsis, and multiple organ failure.[3,4,5]

HS induces excessive production of inflammatory cytokines which leads to HPCs apoptosis.[4,5] Robinson et al. reported that tumor necrosis factor-α binds to the receptor on BM, which activates caspase-8 leading to apoptosis in severe trauma.[5] Maturation of erythroid progenitor cells was inhibited by interleukin 1 (IL-1), IL-6, IL-8, and transforming growth factor-β in severe trauma.[4,5] BM dysfunction is also associated with mobilization of HPCs into the peripheral blood from BM following severe trauma and animal model.[6]

Hematopoietic stem cells (HSCs) are blood cells that differentiate into the myeloid and lymphoid lineage. BM-derived stem and progenitor cells have a capacity for self-renewal, differentiation, survival, migration, and proliferation. Their mobilization is regulated by an extrinsic and intrinsic signal provided by their microenvironment. BM HPCs are thought to be located within specific stromal niches. This specific microenvironment provides soluble factors and cellular interaction required for HPCs proliferation and differentiation. HPCs may move from one niche to another. HSCs can be isolated from the pelvis, femur, sternum, umbilical cord blood, and peripheral blood. Human HSCs are characterized by expression of surface markers of CD34⁺, CD59⁺, Thy1/CD90⁺, CD38^lo/−, C-kit/CD117⁺, lin⁻.[7,8,9]

HSCs transplantation has been used as an adjunct treatment of BM failure, hemoglobinopathies, and immune system disorders.[9,10,11] Li et al. study showed that human hematopoietic stem/progenitor cells (HSPCs) promoted the kidney repair and regeneration using an established ischemia-reperfusion injury model in mice.[12] Human CD34+ cells and HSPCs promoted vasculogenesis and osteogenesis in stroke and bone injury.[13] However, the experience of HSCs transplantation in trauma is limited. Authors feel HSCs transplantation may be explored as a therapeutic option in various research models of trauma/HS.