Hematopoietic Stem/Progenitor Cell Mobilization in Donors and Recipients after Living Donor Liver Transplantation

Combination therapy with interferon-α and anti-viral drug is the current treatment of choice for chronic hepatitis viral infection. However, an important number of patients fail to respond to this therapeutic strategy and develop cirrhosis or liver cancer. Liver transplantation (mainly living donor liver transplantation (LDLT) in Japan) is known to be the ultimate therapy for them. To clarify the association of liver regeneration and hematopoietic stem/progenitor cells (HSCs), we quantified the number of circulating CD34⁺ cells (CD34⁺ cell number) and serum concentration of thrombopoietin (TPO) before and after surgery in 10 donors and 9 recipients undergoing LDLT. The evaluation of CD34⁺ cells has been carried out by flow cytometry, by applying conventional protocols. In donors, CD34⁺ cell number increased from 3.69 ± 2.87 cells/μL at pre-LDLT to 8.25 ± 4.94 cells/μL at post-operative day (POD) 7. Platelet count increased from 209 ± 50 × 109/L at pre-LDLT to 273 ± 23 × 109/L at POD 7–11. In recipients, although CD34⁺ cell number was 0.78 ± 0.73 cells/μL at pre-LDLT and significantly lower than that in healthy volunteers (3.78 ± 3.93 cells/μL), the number at POD 9–42 increased to 4.25 ± 3.55 cells/μL. Platelet count increased from 64 ± 35 × 109/L at pre-LDLT to 197 ± 91 × 109/L at POD 9–42. Serum TPO concentration at pre-LDLT was 0.98 ± 0.61 fmol/L in donors and 1.00 ± 0.35 fmol/L in recipients. TPO level peaked at POD 3–7 (3.14 ± 1.67 fmol/L) in donors and at POD 7–22 (6.74 ± 3.13 fmol/L) in recipients. It has been reported that mobilization of HSCs after partial hepatectomy in donors or LDLT in recipients was likely enhanced by increased serum levels of granulocyte colony-stimulating factor (peaked at POD 1), interleukin-6 and stem cell factor (POD 7). However, in our study, TPO (peaked at POD 7–22) was strongly associated with not only the increase of platelet count (peaked at POD 9–42) but also the mobilization of HSCs (POD 9–42) in recipients. Both mobilized HSCs and platelets may contribute to the liver regeneration after LDLT.