Submitted to: Pediatric Research
Publication Type: Peer reviewed journal
Publication Acceptance Date: 8/21/2007
Publication Date: 2/1/2008
Citation: Kienstra, K.A., Jackson, K.A., Hirschi, K.K. 2008. Injury mechanism dictates contribution of bone marrow-derived cells to murine hepatic vascular regeneration. Pediatric Research. 63(2):131-136. Interpretive Summary: Stem cells from adult bone marrow have been shown to contribute to tissue and blood vessel regeneration after injury, but the precise mechanism of their role in healing is unknown. These studies demonstrated that the type of injury to a tissue determines whether cells from the bone marrow are involved in repair. They also showed the bone marrow hematopoietic stem cells are involved in blood vessel regeneration and repair. Thus, for certain types of tissue injury, bone marrow stem cells may be useful in regenerative medicine and healing. Since endothelial cell growth and migration is regulated by nutrients, such as retinoic acid, it is possible that the process of vessel regeneration from bone marrow cells may be nutrient-regulated.
Technical Abstract: Stem and progenitor cells derived from adult marrow have been shown to regenerate vascular cells in response to injury. However, it is unclear whether the type of injury dictates the contribution of such cells to neovascularization and which subpopulations of cells contribute to vascular regeneration. To address these questions, we determined the extent that hematopoietic stem cells (HSC) contributed to blood vessel formation in response to two types of liver injury: partial hepatectomy (PH) and toxin-induced injury. Lac-Z-labeled HSC were engrafted into lethally irradiated, genetically matched recipients. After 14 d, we identified transplanted cells engrafted within the vascular endothelium of toxin-damaged liver, but not in the vasculature of liver regenerated in response to PH. Engraftment of HSC-derived cells occurred in a gradient fashion, with the highest activity in the severely injured areas. Although HSC-derived cells contributed to both microvessels and large vessels, the large caliber vessels trended toward higher engraftment levels. Thus, the contribution of marrow-derived cells to hepatic neovascularization is dependent upon the type of injury sustained. Furthermore, following toxin-induced liver injury, engraftment rates trended higher in large vessels compared with capillaries, suggesting that remodeling of existing vessels is a predominant mechanism of repair, relative to the formation of new microvasculature.