Human Hepatic Progenitor Cells Express Hematopoietic Cell Markers CD45 and CD109

Abstract

Objective: To clarify the precise characteristics of human hepatic progenitor cells (HPCs) for future cytotherapy in liver diseases.Methods: Hepatic progenitor-like cells were isolated and cultured from the livers of patients who had undergone partial hepatectomy for various pathologies but displayed no sign of hepatic dysfunction. These cells were characterized by transcriptomic profiling, quantitative real-time PCR and immunocyto/histochemistry.Results:Cultured HPCs contained polygonal, high nucleus/cytoplasm ratio and exhibited a global gene expression profile similar (67.8%) to that of primary hepatocytes. Among the genes with more than 20-fold higher expression in HPCs were a progenitor marker (CD90), a pentraxin-related gene (PTX3), collagen proteins (COL5A2, COL1A1 and COL4A2), cytokines (EGF and PDGFD), metabolic enzymes (CYBRD1, BCAT1, TIMP2 and PAM), a secreted protein (SPARC) and an endothelial protein C receptor (PROCR). Moreover, eight markers (ALB, AFP, CK8, CK18, CK19, CD90, CD117 and Oval-6) previously described as HPC markers were validated by qRT-PCR and/or immunocyto/histochemistry. Interestingly, human HPCs were also positive for the hematopoietic cell markers CD45 and CD109. Finally, we characterized the localization of HPCs in the canals of Hering and periportal areas with six previously described markers (Oval-6, CK8, CK18, CK19, CD90 and CD117) and two potential markers (CD45 and CD109).Conclusion: The human HPCs are highly similar to primary hepatocytes in their transcriptional profiles. The CD45 and CD109 markers could potentially be utilized to identify and isolate HPCs for further cytotherapy of liver diseases.

Specific Markers for Hepatic Progenitor Cells

“…Another study suggested that HPCs express the same marker as primitive bile duct cells of the ductal plate, AFP, but have different phenotypic features from cholangiocytes and hepatocytes. HPCs characteristic were in the middle between those of stem cells and mature cells (Van Den Heuvel et al, 2001;Petersen et al, 1998;Li et al, 2014;Hao et al, 2013). This finding suggested that HPCs have bipotential capacity to differentiate into both cholangiocytes and hepatocytes.…”

“…HPCs also express cholangiocytes markers (CK19) moderately and HSCs marker (CD45 and CD109) strongly. Akiba et al (2013) CD56, c-kit (CD117), CD133, EpCAM Badrawy et al (2013) OV6, AFP Chen et al (2015) OV6, CK19 Hao et al (2013) EpCAM, CD133, AFP, EFNA1 Jia et al (2013) OV6 Li et al (2014) Alb, AFP, CK8, CK18, CK19, CD90, c-kit (CD117), OV6, CD45, CD109 Libbrecht et al (2000) CK7, CK19, CK8, CK18, Chrom-A, OV6 Petersen et al (1998) AFP, GGT, OV6, CK19, OC2, Thy-1 Van Den Heuvel et al (2001) OV6, CK19 Ye et al (2014) EpCAM, OV6, CD133, c-kit (CD117) Yun et al (2013) CK19, Oct-3/4, EpCAM, DLK1 Yovchev et al (2007) EpCAM, CD44, CD24, CD133 In addition, Ye et al (2014) used four markers for HPCs (EpCAM, OV6, CD133 and c-kit) and found that HPCs express HSCs marker (c-kit and CD133) and express biliary marker (EpCAM). Another HSCs marker used to identify HPCs was Thy-1 (Petersen et al, 1998).…”

“…Several markers for Hematopoietic Stem Cells (HSCs) have been proposed since those markers positive cells were suspected as the origin of hepatic progenitor cells. Li et al (2014) used 10 markers to identify HPCs; eight markers for HPCs (Alb, AFP, CK8, CK18, CK19, CD90, CD117 and OV6) and two markers for HSCs (CD45 and CD109). The similarity of HPCs and hepatocytes were confirmed.…”

Identification of missense mutations in the PCP4 and CD109 genes to validate the effect of neutral genetic markers

“…To our knowledge, no studies have examined the expression of this gene in livestock; on the other hand, in human medicine, CD109 expression was correlated with the pathological grade and tumor stage of some carcinomas (Hagikura et al 2010). Li et al (2013) found that CD109 marker was expressed in the hepatic progenitor cells (HPCs) and suggested that this marker could potentially be utilized to identify and isolate HPCs for further cytotherapy of liver diseases. Finally, Bizet et al (2011) identified CD109 as a TGF-β co-receptor and a negative regulator of TGF-β signalling.…”

α-Imaging Confirmed Efficient Targeting of CD45-Positive Cells After 211At-Radioimmunotherapy for Hematopoietic Cell Transplantation

“…In addition, slightly increased %IA/g is expected for anti-CD45-radioimmunoconjugates due to presence of CD45-expressing cells of hematopoietic origin in the liver (20). Even so, CD45 is attractive for radioimmunotherapy because of its abundance on target cells, and non-internalizing and non-shedding features.…”