Expression of progenitor cell markers in livers with fulminant massive necrosis
Introduction
Stem cells are generally responsible for normal tissue renewal during regeneration following injury [1], [2]. Hepatocytes usually repair hepatic necrosis by mitosis, but if their division is inhibited, oval cells that are thought to develop into hepatocytes and biliary epithelial cells can proliferate [2], [3], [4]. It has recently been reported that the stem cells in bone marrow develop into hematopoietic and mesenchymal lineages in addition to hepatic progenitor cells, oval cells, hepatocytes, or biliary epithelial cells [1], [5], [6], [7], [8], [9], [10], [11], [12]. The oval cells are thought to be progenitor cells in the liver. Moreover, cells positive for cytokeratin 14 (CK14) have recently been reported also to be progenitor cells and are thought to belong to a member of stem cells [13], [14]. The consensus definition of stem cells is likely to include at least three ideas [5]: stem cells are able to reproduce themselves, they are able to give rise to differentiated cells, and they are also thought to undergo obligatory asymmetric division to yield one stem cell daughter and one daughter destined to differentiate. Significant contribution of stem cells to the regenerative process occurs only under circumstances in which residual differentiated cells are functionally compromised and/or cannot proliferate.
Since it is of great interest to test for the presence of CK14- [10], [11], [13], [14], CD34- [8], [9], vimentin- [13], [15], [16], c-kit- [6], [8], [9], [17], [18], [19], [20], [21], or flt-3- [19], [20] positive cells in hepatic regeneration, we immunohistochemically examined expression of these progenitor cell markers in patients with fulminant massive or confluent necrosis.
Section snippets
Patients and methods
We examined 20 patients with confluent or massive hepatic necrosis. Fourteen of them died of hepatic failure, while the remaining six have survived hepatic failure. All six survivors underwent liver biopsy by Silverman's needle under laparoscopy when they recovered from hepatic failure, and the 14 deceased patients underwent autopsy within 6 h after death. The clinical data on these patients are summarized in Table 1. The patients included 11 women and nine men, ranging in age from 19 to 74
Results
The causative agent of confluent or multi-lobular (massive) necrosis was hepatitis B virus (HBV) infection, drugs or excessive consumption of alcohol (Table 1). The 14 deceased patients were diagnosed as fulminant hepatitis. Three of them were diagnosed as acute type of fulminant hepatitis, and the mean number of days from onset to diagnosis was 5.7. The remaining 11 patients were diagnosed as subacute type of fulminant hepatitis, and the mean number of days from onset to diagnosis was 20.5.
Discussion
Recent reports have surprisingly suggested that tissue-specific adult stem cells have the potential to contribute to replenishment of multiple adult tissues [1], [2], [3], [4], [5]. Although studies of liver regeneration have progressed [1], [2], [3], [4], [10], the stem cells, primordial cells, and progenitor cells, including oval cells, in adult human liver have not been thoroughly elucidated [2], [5], [11], [12]. Recently, CK14, CD34, c-kit, and flt-3 have been recognized to be markers of
References (28)
- et al.
Liver from bone marrow in humans
Hepatology
(2000) - et al.
Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium
Gastroenterology
(2001) - et al.
Identification of biopotential progenitor cells in human liver development
Hepatology
(1996) - et al.
Coexpression of stem cell factor and c-kit in embryonic and adult liver
Exp. Cell Res.
(1996) - et al.
Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver
Hepatology
(2000) - et al.
Liver regeneration
Science
(1997) Stem cells in epithelial tissues
Science
(2000)- et al.
Bile ductular damage induced by methylene diamine inhibits oval cell activation
Am. J. Pathol.
(1997) - et al.
Occurrence of oval-type cells in hepatitis B virus-associated human hepatocarcinogenesis
Hepatology
(1992) - et al.
Bone marrow as a potential source of hepatic oval cells
Science
(1999)
Expression of the stem cell factor receptor c-kit in normal and diseased pediatric liver: identification of a human hepatic progenitor cell
Hepatology
Hepatocytes from non-hepatic adult stem cells
Nature
Hepato–cellular carcinoma expressing both hepatocellular and biliary markers also express cytokeratin 14, a marker of bipotential progenitor cells
J. Hepatol.
Hepatic stem cells in liver regeneration
FASEB J.
Cited by (15)
Liver renewal: Detecting misrepair and optimizing regeneration
2014, Mayo Clinic ProceedingsCitation Excerpt :This discovery, in turn, helps us explain why TGF-β, a known EMT-promoting factor,45 is important for the myofibroblastic transdifferentiation of HSCs,46-48 as well as several earlier reports that indicated that the overexpression of bone morphogenic protein-7 (BMP-7), a potent EMT inhibitor, prevented and/or reversed fibrosis in various rodent liver injury models.49-51 Like MFs, cells expressing progenitor markers are fairly inconspicuous in healthy adult livers, but rapidly accumulate during various types of liver injury.52-55 Interestingly, progenitors and MFs generally intermingle in areas of scarring.
Extramedullary haematopoiesis in liver of sudden infant death cases
2007, Forensic Science InternationalCitation Excerpt :Sequeira Lopez et al. [22] found that rennin–angiotensin system played a role in erythropoietic differentiation. Progenitor cells have been confirmed even in liver by the recognition of cytokeratin 14 (CK14), c-kit [23], flt-3 [24], and CD 34 [2,24,25]. Since c-kit has been used as a haematopoietic marker, CK14 and c-kit-positive cells may be derived from bone marrow in liver with fulminate hepatitis.
Biliary phenotype of hepatocellular carcinoma after preoperative transcatheter arterial chemoembolization
2008, Journal of Gastroenterology and Hepatology (Australia)