Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats

Abstract

The ability of the liver to regenerate is crucial to protect liver function after injury and during chronic disease. Increases in hepatocyte growth factor (HGF) in liver sinusoidal endothelial cells (LSECs) are thought to drive liver regeneration. However, in contrast to endothelial progenitor cells, mature LSECs express little HGF. Therefore, we sought to establish in rats whether liver injury causes BM LSEC progenitor cells to engraft in the liver and provide increased levels of HGF and to examine the relative contribution of resident and BM LSEC progenitors. LSEC label-retaining cells and progenitors were identified in liver and LSEC progenitors in BM. BM LSEC progenitors did not contribute to normal LSEC turnover in the liver. However, after partial hepatectomy, BM LSEC progenitor proliferation and mobilization to the circulation doubled. In the liver, onequarter of the LSECs were BM derived, and BM LSEC progenitors differentiated into fenestrated LSECs. When irradiated rats underwent partial hepatectomy, liver regeneration was compromised, but infusion of LSEC progenitors rescued the defect. Further analysis revealed that BM LSEC progenitors expressed substantially more HGF and were more proliferative than resident LSEC progenitors after partial hepatectomy. Resident LSEC progenitors within their niche may play a smaller role in recovery from partial hepatectomy than BM LSEC progenitors, but, when infused after injury, these progenitors engrafted and expanded markedly over a 2-month period. In conclusion, LSEC progenitor cells are present in liver and BM, and recruitment of BM LSEC progenitors is necessary for normal liver regeneration.

Liver sinusoidal endothelial cells and liver regeneration

“…Two populations of liver sinusoidal endothelial cell progenitor cells (SPCs) have been identified: BM SPCs and resident or intrahepatic SPCs. BM SPCs do not contribute to normal LSEC turnover, but are recruited to the liver after injury or partial hepatectomy (5,33,35). Resident SPCs are not derived from the bone marrow in the adult rodent (5).…”

“…Finally, a recent paper has suggested that impaired liver regeneration in mice with inducible genetic ablation of VEGFR2 is due to diminished expression of angiocrine factors, including HGF, from LSECs (4). However, like other endothelial cells, LSECs express very little HGF (1,5). In contrast, bone marrow progenitor cells of LSECs (BM SPCs), which are recruited to the liver after injury and after partial hepatectomy (5), are rich in HGF.…”

“…However, like other endothelial cells, LSECs express very little HGF (1,5). In contrast, bone marrow progenitor cells of LSECs (BM SPCs), which are recruited to the liver after injury and after partial hepatectomy (5), are rich in HGF. BM SPCs are the same size as LSECs and share surface markers (5); therefore, LSEC isolation methods can also recover BM SPCs engrafted in the liver along with LSECs.…”

LYVE1 and PROX1 in the reconstruction of hepatic sinusoids after partial hepatectomy in mice

“…Liver sinusoidal endothelial cells have an essential role during liver regeneration, as these cells, originating from bone marrow, have been found to promote hepatocyte proliferation and accelerate liver mass repair in response to injury [30]. However, the molecular mechanisms involved in these processes remain largely unknown.…”

Immune system and regulation of regeneration

“…Оказалось, что синусоидальные ýндотелиальные клетки продуцируют HGF, при ýтом клетки-предшественницы в ýтом отношении более активны, чем зрелые ýндотелиоциты. При повреждении печени в орган мигрируют кост-номозговые предшественники синусоидальных ýндотелиальных клеток, которые стимулируют репаративные процессы значительно больше, чем резидентные клетки [40].N.F. Liu, Q.L.…”