Review Open Access
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2014; 20(27): 9098-9105
Published online Jul 21, 2014. doi: 10.3748/wjg.v20.i27.9098
Bone marrow derived stem cells for the treatment of end-stage liver disease
Cristina Margini, Ranka Vukotic, Lucia Brodosi, Mauro Bernardi, Pietro Andreone, Dipartimento di Scienze mediche e Chirurgiche, Unità Operativa di Semeiotica Medica, University of Bologna, 40138 Bologna, Italy
Author contributions: Margini C conceived of and designed the study, performed the literature search and critical analyses, interpreted and contextualized the available data, drafted the manuscript and revised it for scientific content; Vukotic R contributed to the interpretation of the collected data, drafted the article and revised the manuscript for scientific content; Brodosi L contributed to revising the paper for scientific content; Bernardi M revised the draft for scientific content; Andreone P conceived of and designed the study, contributed to the interpretation of the data and to the revision of the draft for scientific content, and is the guarantor of this review article; all authors approved the final version of the manuscript.
Correspondence to: Pietro Andreone, MD, Professor of Internal Medicine, Dipartimento di Scienze mediche e Chirurgiche, Unità Operativa di Semeiotica Medica, University of Bologna, Padiglione 11, Via Massarenti 9, 40138 Bologna, Italy. pietro.andreone@unibo.it
Telephone: +39-51-6364107 Fax: +39-51-345806
Received: October 29, 2013
Revised: February 27, 2014
Accepted: April 15, 2014
Published online: July 21, 2014

Abstract

End-stage disease due to liver cirrhosis is an important cause of death worldwide. Cirrhosis results from progressive, extensive fibrosis and impaired hepatocyte regeneration. The only curative treatment is liver transplantation, but due to the several limitations of this procedure, the interest in alternative therapeutic strategies is increasing. In particular, the potential of bone marrow stem cell (BMSC) therapy in cirrhosis has been explored in different trials. In this article, we evaluate the results of 18 prospective clinical trials, and we provide a descriptive overview of recent advances in the research on hepatic regenerative medicine. The main message from the currently available data in the literature is that BMSC therapy is extremely promising in the context of liver cirrhosis. However, its application should be further explored in randomized, controlled trials with large cohorts and long follow-ups.

Key Words: Liver cirrhosis, Liver regeneration, Hematopoietic stem cells, Mesenchymal stem cells, End stage liver disease

Core tip: In recent years, the role of bone marrow stem cells (BMSCs) in liver regeneration has been explored in various clinical trials. Because these trials were very diverse, we conducted a descriptive overview to understand the effects of BMSC transplantation on liver histology and morphology, on laboratory parameters and prognostic scores, and finally, on clinical manifestations and quality of life. This overview suggests that the efficacy of BMSC therapy might be temporary, and therefore, repeated cycles of BMSCs could be useful to achieve a sustained benefit.



INTRODUCTION

End-stage disease due to liver cirrhosis is an important cause of death worldwide[1-3]. Currently, the only effective treatment is liver transplantation, but because of the lack of organ donors, surgical complications, risk of rejection and high costs[4,5], the pressure on finding new treatment strategies is increasing[6]. When a successful etiologic approach is unavailable or has failed, progressive, extensive fibrosis[7,8] with concurrently impaired hepatocyte regeneration[9,10] leads to irreversible cirrhosis[11,12]. Therefore, the development of new techniques to stimulate liver regeneration and reduce the scarring process is urgently needed. In this respect, there is great interest in the potential of BMSC therapy to promote liver regeneration through the use of unsorted mononuclear stem cells (MNCs), hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). This review article summarizes the results of the main prospective clinical trials on BMSC transplantation in patients with cirrhosis, providing a descriptive overview of recent advances in the research on hepatic regenerative medicine.

Liver fibrosis

Cirrhosis is the common final outcome of chronic liver disease, leading to portal hypertension and end-stage liver disease (ESLD), and it is mainly caused by alcohol abuse and viral infections. The prevalence is estimated at 0.15% in the United States[6], and liver cirrhosis-related deaths constitute 1.8% of all deaths in Europe[13].

The main pathogenetic mechanism that leads to the subversion of liver architecture is an aberrant healing process referred to as fibrogenesis, which can be triggered by various factors such as viruses, alcohol abuse, steatohepatitis, autoantibodies, oxidative stress, and others. The common pathway leading to the deposition of extracellular matrix (ECM) is the activation of myofibroblasts. Myofibroblasts originate from different sources such as hepatic stem cells, portal fibroblasts and bone marrow (BM) derived fibrocytes (haematopoietic lineage) and mesenchymal cells. These cells can also arise from epithelial cells via epithelial to mesenchymal transition[8,14]. In the first phase of hepatic injury, the production of ECM is counterbalanced by the action of proteolytic enzymes such as matrix metalloproteinases (MMPs). With persistent damage, this equilibrium is compromised, and the presence of tissue inhibitors of MMPs abnormally enhances the deposition of ECM and ultimately leads to the alteration of normal liver structure[15].

Liver regeneration

The processes and the pathways responsible for liver regeneration are not yet completely understood. Under physiological circumstances, the ability of hepatocytes to re-enter the cell cycle enables liver regeneration and repair through compensatory hyperplasia and hypertrophy[16-18]. In the case of chronic liver injury, this ability is compromised, and liver regeneration is carried out by liver progenitor cells (LPCs). Progenitor-dependent regeneration takes place if hepatocytes are severely damaged and unable to regenerate efficiently, as occurs in cirrhosis. This hypothesis was first suggested by the finding that the LPC concentration in patients with chronic liver disease is greatly increased[19].

These cells were initially identified in animal models and called “oval cells”. It has been demonstrated that they are a bi-potential progenitor for hepatocytes and biliary cells[20]. Highly conserved intracellular pathways are responsible for oval cell differentiation. In particular, Wnt signalling is involved in LPC proliferation, while Notch signalling is involved in biliary differentiation[21]. The human equivalent of oval cells have been detected in the canal of Hering, and according to the so called “streaming liver hypothesis”, these cells migrate to the central vein and progressively differentiate into hepatocytes[22,23]. Conversely, Kuwahara et al[24] have suggested that LPCs can be located in four different cell niches: canal of Hering, intralobular bile ducts, periductular mononuclear cells and peribiliary hepatocytes. The space of Disse has also been reported to be a potential niche for LPCs[25].

The origin of LPCs is controversial; they might be in situ cells, descendants of the foetal ductal plate[26], or derive from BMSCs, as first described by Petersen et al[27]. Furthermore, it has also been hypothesized that they might arise from MSCs via the mesenchymal to epithelial transition[28].

Using Y chromosome tracking in rodents[29] and humans[30], it has also been reported that BMSCs may contribute to hepatocyte differentiation independently of mature hepatocytes and LPCs. This limited evidence highlights the fact that liver regeneration processes are not yet fully understood, and only with a better understanding of these molecular and cellular mechanisms will it be possible to develop a targeted therapy for liver fibrosis.

STEM CELL THERAPY

In recent years, unsorted MNCs, HSCs and MSCs have been employed in research focused on liver regeneration[31,32].

HSCs are traceable using CD34 and CD133 markers. The latter is believed to represent a subpopulation of the CD34+ cells that have a higher differentiation potential[33]. HSCs can be obtained by BM aspiration or from peripheral collection through leukapheresis after granulocyte-colony stimulating factor (G-CSF) administration, whereas MNCs and MSCs can be harvested mainly by BM aspiration, which requires an invasive procedure. G-CSF has been used in liver regeneration because of its ability to increase the number of circulating BMSCs and to promote repair in the cirrhotic liver[34]. As suggested by Jin et al[35], G-CSF may also enhance MNC homing to the liver.

The feasibility and safety of mobilizing BM derived cells following G-CSF administration was demonstrated by Gaia et al[36] in eight patients with ESLD. Additionally, this study reported improved model for end-stage liver disease (MELD) scores and did not find any development of hepatocellular carcinoma or increase in alpha-fetoprotein up to eight months after G-CSF administration. A favourable effect of G-CSF administration on survival and clinical parameters in patients with liver failure has also been reported in other studies[37]. Lorenzini et al[38] demonstrated the safety of BMSC mobilization and collection through leukapheresis in patients with cirrhosis, even though no improvement of liver function tests occurred. G-CSF administration can be also associated with the risk of spleen enlargement[39] or even rupture, as reported by Falzetti et al[40] in a healthy donor.

Other cells that have been utilized in hepatic regeneration research include foetal annex stem cells (cord blood and placenta) and embryonic stem cells[41,42]. The use of embryonic stem cells is limited to in vitro and animal studies because of difficulties in controlling their proliferative and differentiation potential. Another type of cell employed in animal experiments is induced pluripotent stem cells, which are embryonic-like stem cells derived from somatic cells through the expression of reprogramming factors[43].

Hypothesized mechanisms

Stem cell therapy may contribute to the improvement of liver function[44]. Although the mechanisms involved are not yet fully understood, some hypotheses have been proposed[45,46]. One hypothesis is that genomic plasticity, in response to the microenvironment, causes the trans-differentiation of stem cells into functional hepatocytes[47,48]. Another mechanism is presumably related to the cell fusion of BMSCs and hepatocytes[49,50]. Additionally, it has been proposed that stem cells may exert paracrine effects on endogenous hepatocytes to increase their ability to regenerate, through the release of proliferative cytokines and the production of matrix metalloproteinase-9[51] or by enhancing angiogenesis through the release of vascular endothelial growth factors[52]. A better understanding of the action of stem cells in the context of a fibrotic liver might allow more rational use of BMSC therapy in liver cirrhosis.

CLINICAL TRIALS

Many clinical trials have recently been published on BMSC therapy in cirrhotic patients. The results of the main prospective clinical trials are summarized in Table 1. These studies differ with respect to study design, inclusion/exclusion criteria, type and number of cells infused, route of delivery and end points. The stage of cirrhosis varied from Child Turcotte Pugh score (CTP) A to C. Although cells were harvested mainly by BM aspiration, in some studies, leukapheresis after G-CSF administration was performed. Different types of cells were infused, including MNCs, MSCs or HSCs. The number of injected cells varied from 106 to 109. The most commonly used routes of delivery were the hepatic artery or portal vein, but in some studies, peripheral vein and intrasplenic injection were also utilized.

Table 1 Prospective studies on bone marrow stem cells therapy in patients with cirrhosis.
Ref.Study designNo. of patientsDisease cause/stageCell/harvestInfusion route/n cell infused
Park et al[69]Case series5MixedMNCs (MSCs)Hepatic artery
Cytotherapy, 2013CTP B-CBM aspiration106-107/kg
Amin et al[64]Case series20HCVMSCsIntrasplenic
Clin Transplant, 2013CTP CBM aspiration107
Mohamadnejad et al[57]Randomized15MixedMSCs/placeboPeripheral vein
Liver Int, 2013Vs untreated control12 controlCTP A-CBM aspiration108
Jang et al[59]Case series12AlcoholMSCsHepatic artery
Liver Int, 2013CTP A-BBM aspiration107
Salama et al[68]Not-randomized50HCVHSCsPortal vein/hepatic artery
Stem Cell Res Ther, 2012Vs untreated control50 controlESLDLeukapheresis
G-CSF109
El-Ansary et al[65]Not-randomized15HCVMSCsPeripheral vein
Stem Cell Rev, 2012Vs untreated control10 controlCTP CBM aspiration106
Peng et al[61]Not-randomized53HBVMSCsHepatic artery
Hepatology, 2011Vs untreated control105 controlMixed1BM aspirationNA
Couto et al[53]Case series8MixedMNCsHepatic artery
Liver Int, 2010CTP B-CBM aspiration109
Nikeghbalian et al[58]Case series6MixedMNCs/HSCsPortalvein
Arch Iran Med, 2011CTP CBM aspiration106-109
Salama et al[66]Randomized90HCVHSCsPortal vein
World J Gastroenterol, 2010Vs untreated control50 controlNABM aspiration107
G-CSF
Kim et al[56]Case series10HBVMNCsPeripheral vein
Cell Transplantation, 2010MELD 7-13BM aspiration108/kg
Lyra et al[62]Randomized15MixedMNCsHepatic artery
Eur J Gastroenterol Hepatol, 2009Vs untreated control15 controlCTP B-CBM aspiration108
Kharaziha et al[67]Case series8MixedMSCsPortal vein
Eur J Gastroenterol Hepatol, 2009MELD > 10BM aspiration108
Pai et al[63]Case series9alcoholHSCsHepatic artery
AM J Gastroenterol, 2008CTP BLeukapheresis108
G-CSF
Levicar et al[54]Case series5MixedHSCsPortalvein/
Cell Proliferat, 2008CTP A-BLeukapheresishepaticartery
G-CSF108
Mohamadnejad et al[55]Case series4MixedHSCsHepatic artery
World J Gastroenterol, 2007CTP B-CBM aspiration106-107
Lyra et al[70]Case series10MixedMNCsHepatic artery
World J Gastroenterol, 2007CTP B-CBM aspiration108
Terai et al[44]Case series9MixedMNCsPeripheral vein
Stem cells, 2006CTP B-CBM aspiration109
Safety of BMSCs therapy

The majority of the clinical trials demonstrated the safety of the procedure. Couto et al[53] reported a case of artery dissection and a case of Tako-Tsubo syndrome after the injection of BMSCs through the hepatic artery, and Levicar et al[54] reported thrombocytopenia after leukapheresis. Finally, Mohamadnejad et al[55] reported a case of radiocontrast nephropathy that progressed to type 1 hepatorenal syndrome and caused the death of a patient. For this reason, the clinical trial was prematurely stopped, and BMSC therapy through the hepatic artery was not considered safe.

Effect of BMSCs therapy on liver histology and morphology

In a study by Kim et al[56], which enrolled ten patients, a significant increase in liver volume compared to baseline was documented using MRI six months after MNCs transplantation through a peripheral injection but this result has not been confirmed[57,58]. In that study, serial biopsies were performed. All biopsies at baseline showed low levels of LPC activation and differentiation. After BMSC therapy, a gradual increase in the LPC count occurred in all patients, with a peak three months after reinfusion. In contrast, no changes in the degree of stellate cell activation were observed[56].

Terai et al[44] demonstrated increased expression of proliferating cell nuclear antigen in liver biopsy tissue one month after peripheral MNC injection. Jang et al[59] performed a histological evaluation in eleven patients with alcohol-induced cirrhosis after two MSC transplantations through the hepatic artery. After five months, significant histological improvement according to the Laennec system[60] was observed, along with a significant decrease in the expression of transforming growth factor-beta1, type I-collagen and alpha-smooth muscle actin.

An interesting study by Couto et al[53] suggested that the hepatic retention of MNCs is fair. In that study, MNCs (MSCs and HSCs) were labelled with Tc99 and then injected through the hepatic artery in eight patients with CTP B and C. Remarkably, whole body scintigraphy at 3 and 24 h after injection showed a mean radiotracer retention of 41% and 32%, respectively. Few studies have evaluated liver histology and morphology, but the available data are consistent with histological improvement, increased LPC count and decreased expression of fibrosis markers after BMSC therapy.

Effect of BMSC therapy on laboratory parameters and prognostic scores

The efficacy of BMSC therapy in patients with cirrhosis was assessed using laboratory parameters such as International Normalized Ratio (INR), total bilirubin (TBil), creatinine (Cr), albumin (Alb) and/or prognostic scores (CTP and MELD). These results are summarized in Table 2.

Table 2 Studies that reported a modification of laboratory parameters and prognostic scores.
AuthorResults compared toLaboratory parameters
Prognostic scores
INRTBilAlbCrMELDCTP
Amin et al[64]BaselineIIINRNRNR
Mohamadnejad et al[57]Control groupNINRNINRNINI
Jang et al[59]BaselineINIINIII
Salama et al[68]BaselineNRINRNRNRNR
El-Ansary et al[65]Control groupI1IINRINR
Peng et al[61]Control groupIIINRINR
Couto et al[53]BaselineNRIINRNRNR
Salama et al[66]Control groupNRIINRNRNR
Kim et al[56]BaselineINRINRNII
Lyra et al[62]BaselineNRNRINRNII
Kharaziha et al[67]BaselineININIIINR
Pai et al[63]BaselineNRININRNRNR
Terai et al[44]BaselineNRNRINRNRI

Significant improvements in laboratory tests were reported at one month after BMSC infusion in one study[53], at three months in four studies[59,61-63], at six months in six studies[44,56,64-67] and after twelve months of follow up in one study[68]. In the remaining studies, the limited number of patients enrolled prevented statistical evaluation, but some improvement in laboratory tests was reported[54,69,70].

A significant improvement in MELD and/or CTP score three months after BMSCs infusion in two studies[59,62], at six months in four studies[44,56,65,67] and at nine months in one study[61] has also been described.

However, the controlled randomized clinical trial performed by Mohamadnejad et al[57] did not show any significant difference in either INR or prognostic scores between treatment and control groups at three and twelve months after BMSCs infusion. The majority of the clinical trials showed a significant but time-limited improvement in laboratory parameters and prognostic scores, offering encouraging prospects for future trials.

Effect of BMSC therapy on clinical manifestations and quality of life

Many studies have evaluated the clinical manifestations associated with ESLD, including hepatic encephalopathy, lower limb oedema, hematemesis, ascites and jaundice. Seven studies reported an improvement in at least one of the previously mentioned clinical manifestations[44,56,63-66,68]. However, it should be noted that some clinical manifestations, such as ascites, might not accurately reflect efficacy. In fact, ascites can be over- or underestimated by physical examination and can be modified by pharmacological interventions other than BMSC therapy (e.g., diuretics, albumin).

Health-related quality of life after BMSC therapy was the primary outcome in an interesting study performed by Salama et al[68]. One hundred patients were assigned to the treatment or control groups and completed the Short Form-36 health status evaluation. Self-reported physical and mental status significantly improved in the treatment group during the six months following BMSC reinfusion, while status significantly deteriorated in the control group; these data are also supported by another recent study[56].

In addition, Salama et al[68] reported a significantly higher survival rate in the treatment group compared to the control group. An improved survival rate after BMSC therapy was also reported in other studies, but the data were not statistically significant[61,66]. In summary, clinical manifestations, health-related quality of life and survival rate have been reported to be improved after BMSCs therapy.

CONCLUSION

There are still many open questions concerning BMSC therapy for the treatment of liver cirrhosis. First, it is crucial to understand the homing processes of BMSCs to the liver and to elucidate the relationships that exist not only between BMSCs and hepatocytes (regeneration) but also between MSCs, myofibroblasts and stellate cells (fibrogenesis). It is essential to clarify the mechanisms by which different types of BMSCs act in the liver, as this would allow the tailoring of stem cell therapy to the specific patient. The hypothesis that BMSCs act through the delivery of specific substances (cytokines and growth factors), rather than through transdifferentiation or cell fusion, suggests that improvements in liver function might be temporary. This hypothesis is supported by the results of the majority of the clinical trials: the improvement in laboratory data and CTP and MELD scores did not persist longer than three-six months regardless of the type of BMSCs infused, the route of delivery or the aetiology of the disease. In addition, the histological evaluations support this hypothesis, as an increase in LPC count was documented, peaking three months after BMSCs infusion. These results suggest that repeated cycles of BMSC therapy could be useful to obtain a sustained benefit.

BMSC therapy, although promising, needs to be further evaluated in large randomized, controlled clinical trials with longer follow-ups because the characteristics of the study populations reported in the current literature do not allow analytic comparison between the studies. In particular, a crucial issue is the different types of stem cells used, and in this regard, it could be interesting to compare the effects of the different types of BMSCs (unsorted MNCs, MSCs, and HSCs) on objective liver function parameters.

Footnotes

P- Reviewers: Kan L, Minana MD, Rameshwar P S- Editor: Zhai HH L- Editor: A E- Editor: Liu XM

References
1.  Lim YS, Kim WR. The global impact of hepatic fibrosis and end-stage liver disease. Clin Liver Dis. 2008;12:733-746, vii.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 215]  [Cited by in F6Publishing: 227]  [Article Influence: 14.2]  [Reference Citation Analysis (0)]
2.  D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44:217-231.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1892]  [Cited by in F6Publishing: 1885]  [Article Influence: 104.7]  [Reference Citation Analysis (1)]
3.  Asrani SK, Kamath PS. Natural history of cirrhosis. Curr Gastroenterol Rep. 2013;15:308.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 1]  [Reference Citation Analysis (0)]
4.  Lucey MR, Terrault N, Ojo L, Hay JE, Neuberger J, Blumberg E, Teperman LW. Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Liver Transpl. 2013;19:3-26.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 329]  [Cited by in F6Publishing: 326]  [Article Influence: 29.6]  [Reference Citation Analysis (0)]
5.  Crespo G, Mariño Z, Navasa M, Forns X. Viral hepatitis in liver transplantation. Gastroenterology. 2012;142:1373-1383.e1.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 156]  [Cited by in F6Publishing: 160]  [Article Influence: 13.3]  [Reference Citation Analysis (0)]
6.  Schuppan D, Afdhal NH. Liver cirrhosis. Lancet. 2008;371:838-851.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1446]  [Cited by in F6Publishing: 1426]  [Article Influence: 89.1]  [Reference Citation Analysis (0)]
7.  Török NJ. Recent advances in the pathogenesis and diagnosis of liver fibrosis. J Gastroenterol. 2008;43:315-321.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 42]  [Cited by in F6Publishing: 45]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]
8.  Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005;115:209-218.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3381]  [Cited by in F6Publishing: 3780]  [Article Influence: 198.9]  [Reference Citation Analysis (3)]
9.  Wiemann SU, Satyanarayana A, Tsahuridu M, Tillmann HL, Zender L, Klempnauer J, Flemming P, Franco S, Blasco MA, Manns MP. Hepatocyte telomere shortening and senescence are general markers of human liver cirrhosis. FASEB J. 2002;16:935-942.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 374]  [Cited by in F6Publishing: 361]  [Article Influence: 16.4]  [Reference Citation Analysis (0)]
10.  Mormone E, George J, Nieto N. Molecular pathogenesis of hepatic fibrosis and current therapeutic approaches. Chem Biol Interact. 2011;193:225-231.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 179]  [Cited by in F6Publishing: 188]  [Article Influence: 14.5]  [Reference Citation Analysis (0)]
11.  Pinzani M, Rosselli M, Zuckermann M. Liver cirrhosis. Best Pract Res Clin Gastroenterol. 2011;25:281-290.  [PubMed]  [DOI]  [Cited in This Article: ]
12.  Pinzani M, Macias-Barragan J. Update on the pathophysiology of liver fibrosis. Expert Rev Gastroenterol Hepatol. 2010;4:459-472.  [PubMed]  [DOI]  [Cited in This Article: ]
13.  Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013;58:593-608.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 879]  [Cited by in F6Publishing: 868]  [Article Influence: 78.9]  [Reference Citation Analysis (0)]
14.  Liu X, Xu J, Brenner DA, Kisseleva T. Reversibility of Liver Fibrosis and Inactivation of Fibrogenic Myofibroblasts. Curr Pathobiol Rep. 2013;1:209-214.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 71]  [Cited by in F6Publishing: 74]  [Article Influence: 6.7]  [Reference Citation Analysis (0)]
15.  Lichtinghagen R, Michels D, Haberkorn CI, Arndt B, Bahr M, Flemming P, Manns MP, Boeker KH. Matrix metalloproteinase (MMP)-2, MMP-7, and tissue inhibitor of metalloproteinase-1 are closely related to the fibroproliferative process in the liver during chronic hepatitis C. J Hepatol. 2001;34:239-247.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 97]  [Cited by in F6Publishing: 101]  [Article Influence: 4.4]  [Reference Citation Analysis (0)]
16.  Orstavik D, Mjör IA. Usage test of four endodontic sealers in Macaca fascicularis monkeys. Oral Surg Oral Med Oral Pathol. 1992;73:337-344.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1091]  [Cited by in F6Publishing: 1115]  [Article Influence: 55.8]  [Reference Citation Analysis (0)]
17.  Fausto N, Campbell JS, Riehle KJ. Liver regeneration. Hepatology. 2006;43:S45-S53.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1126]  [Cited by in F6Publishing: 1146]  [Article Influence: 63.7]  [Reference Citation Analysis (0)]
18.  Miyaoka Y, Miyajima A. To divide or not to divide: revisiting liver regeneration. Cell Div. 2013;8:8.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 96]  [Cited by in F6Publishing: 103]  [Article Influence: 9.4]  [Reference Citation Analysis (0)]
19.  Libbrecht L, Roskams T. Hepatic progenitor cells in human liver diseases. Semin Cell Dev Biol. 2002;13:389-396.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 156]  [Cited by in F6Publishing: 147]  [Article Influence: 6.7]  [Reference Citation Analysis (0)]
20.  Dezső K, Papp V, Bugyik E, Hegyesi H, Sáfrány G, Bödör C, Nagy P, Paku S. Structural analysis of oval-cell-mediated liver regeneration in rats. Hepatology. 2012;56:1457-1467.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 31]  [Cited by in F6Publishing: 33]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]
21.  Spee B, Carpino G, Schotanus BA, Katoonizadeh A, Vander Borght S, Gaudio E, Roskams T. Characterisation of the liver progenitor cell niche in liver diseases: potential involvement of Wnt and Notch signalling. Gut. 2010;59:247-257.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 145]  [Cited by in F6Publishing: 160]  [Article Influence: 11.4]  [Reference Citation Analysis (0)]
22.  Fellous TG, Islam S, Tadrous PJ, Elia G, Kocher HM, Bhattacharya S, Mears L, Turnbull DM, Taylor RW, Greaves LC. Locating the stem cell niche and tracing hepatocyte lineages in human liver. Hepatology. 2009;49:1655-1663.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 126]  [Cited by in F6Publishing: 132]  [Article Influence: 8.8]  [Reference Citation Analysis (0)]
23.  Lin WR, Lim SN, McDonald SA, Graham T, Wright VL, Peplow CL, Humphries A, Kocher HM, Wright NA, Dhillon AP. The histogenesis of regenerative nodules in human liver cirrhosis. Hepatology. 2010;51:1017-1026.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 81]  [Cited by in F6Publishing: 75]  [Article Influence: 5.4]  [Reference Citation Analysis (0)]
24.  Kuwahara R, Kofman AV, Landis CS, Swenson ES, Barendswaard E, Theise ND. The hepatic stem cell niche: identification by label-retaining cell assay. Hepatology. 2008;47:1994-2002.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 202]  [Cited by in F6Publishing: 191]  [Article Influence: 11.9]  [Reference Citation Analysis (0)]
25.  Kordes C, Häussinger D. Hepatic stem cell niches. J Clin Invest. 2013;123:1874-1880.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 100]  [Cited by in F6Publishing: 106]  [Article Influence: 9.6]  [Reference Citation Analysis (0)]
26.  Zhang L, Theise N, Chua M, Reid LM. The stem cell niche of human livers: symmetry between development and regeneration. Hepatology. 2008;48:1598-1607.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 191]  [Cited by in F6Publishing: 174]  [Article Influence: 10.9]  [Reference Citation Analysis (0)]
27.  Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP. Bone marrow as a potential source of hepatic oval cells. Science. 1999;284:1168-1170.  [PubMed]  [DOI]  [Cited in This Article: ]
28.  Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Quinn G, Okochi H, Ochiya T. Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology. 2007;46:219-228.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 408]  [Cited by in F6Publishing: 426]  [Article Influence: 25.1]  [Reference Citation Analysis (0)]
29.  Mallet VO, Mitchell C, Mezey E, Fabre M, Guidotti JE, Renia L, Coulombel L, Kahn A, Gilgenkrantz H. Bone marrow transplantation in mice leads to a minor population of hepatocytes that can be selectively amplified in vivo. Hepatology. 2002;35:799-804.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 94]  [Cited by in F6Publishing: 102]  [Article Influence: 4.6]  [Reference Citation Analysis (0)]
30.  Alison MR, Poulsom R, Jeffery R, Dhillon AP, Quaglia A, Jacob J, Novelli M, Prentice G, Williamson J, Wright NA. Hepatocytes from non-hepatic adult stem cells. Nature. 2000;406:257.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 779]  [Cited by in F6Publishing: 737]  [Article Influence: 30.7]  [Reference Citation Analysis (0)]
31.  Lorenzini S, Gitto S, Grandini E, Andreone P, Bernardi M. Stem cells for end stage liver disease: how far have we got? World J Gastroenterol. 2008;14:4593-4599.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 25]  [Cited by in F6Publishing: 29]  [Article Influence: 1.8]  [Reference Citation Analysis (0)]
32.  Fausto N. Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells. Hepatology. 2004;39:1477-1487.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 537]  [Cited by in F6Publishing: 503]  [Article Influence: 25.2]  [Reference Citation Analysis (0)]
33.  de Wynter EA, Buck D, Hart C, Heywood R, Coutinho LH, Clayton A, Rafferty JA, Burt D, Guenechea G, Bueren JA. CD34+AC133+ cells isolated from cord blood are highly enriched in long-term culture-initiating cells, NOD/SCID-repopulating cells and dendritic cell progenitors. Stem Cells. 1998;16:387-396.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 159]  [Cited by in F6Publishing: 166]  [Article Influence: 6.4]  [Reference Citation Analysis (0)]
34.  Mizunaga Y, Terai S, Yamamoto N, Uchida K, Yamasaki T, Nishina H, Fujita Y, Shinoda K, Hamamoto Y, Sakaida I. Granulocyte colony-stimulating factor and interleukin-1β are important cytokines in repair of the cirrhotic liver after bone marrow cell infusion: comparison of humans and model mice. Cell Transplant. 2012;21:2363-2375.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 11]  [Cited by in F6Publishing: 12]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
35.  Jin SZ, Meng XW, Sun X, Han MZ, Liu BR, Wang XH, Sun LY, Huang Q, Zhao RB, Ban X. Granulocyte colony-stimulating factor enhances bone marrow mononuclear cell homing to the liver in a mouse model of acute hepatic injury. Dig Dis Sci. 2010;55:2805-2813.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 19]  [Cited by in F6Publishing: 20]  [Article Influence: 1.4]  [Reference Citation Analysis (0)]
36.  Gaia S, Smedile A, Omedè P, Olivero A, Sanavio F, Balzola F, Ottobrelli A, Abate ML, Marzano A, Rizzetto M. Feasibility and safety of G-CSF administration to induce bone marrow-derived cells mobilization in patients with end stage liver disease. J Hepatol. 2006;45:13-19.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 123]  [Cited by in F6Publishing: 135]  [Article Influence: 7.5]  [Reference Citation Analysis (0)]
37.  Garg V, Garg H, Khan A, Trehanpati N, Kumar A, Sharma BC, Sakhuja P, Sarin SK. Granulocyte colony-stimulating factor mobilizes CD34(+) cells and improves survival of patients with acute-on-chronic liver failure. Gastroenterology. 2012;142:505-512.e1.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 261]  [Cited by in F6Publishing: 264]  [Article Influence: 22.0]  [Reference Citation Analysis (0)]
38.  Lorenzini S, Isidori A, Catani L, Gramenzi A, Talarico S, Bonifazi F, Giudice V, Conte R, Baccarani M, Bernardi M. Stem cell mobilization and collection in patients with liver cirrhosis. Aliment Pharmacol Ther. 2008;27:932-939.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 43]  [Cited by in F6Publishing: 41]  [Article Influence: 2.6]  [Reference Citation Analysis (0)]
39.  Picardi M, De Rosa G, Selleri C, Scarpato N, Soscia E, Martinelli V, Ciancia R, Rotoli B. Spleen enlargement following recombinant human granulocyte colony-stimulating factor administration for peripheral blood stem cell mobilization. Haematologica. 2003;88:794-800.  [PubMed]  [DOI]  [Cited in This Article: ]
40.  Falzetti F, Aversa F, Minelli O, Tabilio A. Spontaneous rupture of spleen during peripheral blood stem-cell mobilisation in a healthy donor. Lancet. 1999;353:555.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 91]  [Cited by in F6Publishing: 107]  [Article Influence: 4.3]  [Reference Citation Analysis (0)]
41.  Campard D, Lysy PA, Najimi M, Sokal EM. Native umbilical cord matrix stem cells express hepatic markers and differentiate into hepatocyte-like cells. Gastroenterology. 2008;134:833-848.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 187]  [Cited by in F6Publishing: 203]  [Article Influence: 12.7]  [Reference Citation Analysis (0)]
42.  Teramoto K, Asahina K, Kumashiro Y, Kakinuma S, Chinzei R, Shimizu-Saito K, Tanaka Y, Teraoka H, Arii S. Hepatocyte differentiation from embryonic stem cells and umbilical cord blood cells. J Hepatobiliary Pancreat Surg. 2005;12:196-202.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 27]  [Article Influence: 1.4]  [Reference Citation Analysis (0)]
43.  Piscaglia AC, Campanale M, Gasbarrini A, Gasbarrini G. Stem cell-based therapies for liver diseases: state of the art and new perspectives. Stem Cells Int. 2010;2010:259461.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 31]  [Cited by in F6Publishing: 33]  [Article Influence: 2.4]  [Reference Citation Analysis (0)]
44.  Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida K, Yamasaki T, Fujii Y. Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells. 2006;24:2292-2298.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 363]  [Cited by in F6Publishing: 338]  [Article Influence: 18.8]  [Reference Citation Analysis (0)]
45.  Kisseleva T, Brenner DA. The phenotypic fate and functional role for bone marrow-derived stem cells in liver fibrosis. J Hepatol. 2012;56:965-972.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 69]  [Cited by in F6Publishing: 71]  [Article Influence: 5.9]  [Reference Citation Analysis (0)]
46.  Lorenzini S, Andreone P. Regenerative medicine and liver injury: what role for bone marrow derived stem cells? Curr Stem Cell Res Ther. 2007;2:83-88.  [PubMed]  [DOI]  [Cited in This Article: ]
47.  Terai S, Sakaida I, Yamamoto N, Omori K, Watanabe T, Ohata S, Katada T, Miyamoto K, Shinoda K, Nishina H. An in vivo model for monitoring trans-differentiation of bone marrow cells into functional hepatocytes. J Biochem. 2003;134:551-558.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 139]  [Cited by in F6Publishing: 153]  [Article Influence: 7.3]  [Reference Citation Analysis (0)]
48.  Jang YY, Collector MI, Baylin SB, Diehl AM, Sharkis SJ. Hematopoietic stem cells convert into liver cells within days without fusion. Nat Cell Biol. 2004;6:532-539.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 430]  [Cited by in F6Publishing: 409]  [Article Influence: 20.5]  [Reference Citation Analysis (0)]
49.  Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Olson S, Grompe M. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature. 2003;422:897-901.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1230]  [Cited by in F6Publishing: 1276]  [Article Influence: 60.8]  [Reference Citation Analysis (0)]
50.  Vassilopoulos G, Wang PR, Russell DW. Transplanted bone marrow regenerates liver by cell fusion. Nature. 2003;422:901-904.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1005]  [Cited by in F6Publishing: 1044]  [Article Influence: 49.7]  [Reference Citation Analysis (0)]
51.  Sakaida I, Terai S, Yamamoto N, Aoyama K, Ishikawa T, Nishina H, Okita K. Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology. 2004;40:1304-1311.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 423]  [Cited by in F6Publishing: 407]  [Article Influence: 20.4]  [Reference Citation Analysis (0)]
52.  Wang L, Wang X, Wang L, Chiu JD, van de Ven G, Gaarde WA, Deleve LD. Hepatic vascular endothelial growth factor regulates recruitment of rat liver sinusoidal endothelial cell progenitor cells. Gastroenterology. 2012;143:1555-1563.e2.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 63]  [Cited by in F6Publishing: 69]  [Article Influence: 5.8]  [Reference Citation Analysis (0)]
53.  Couto BG, Goldenberg RC, da Fonseca LM, Thomas J, Gutfilen B, Resende CM, Azevedo F, Mercante DR, Torres AL, Coelho HS. Bone marrow mononuclear cell therapy for patients with cirrhosis: a Phase 1 study. Liver Int. 2011;31:391-400.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 47]  [Cited by in F6Publishing: 39]  [Article Influence: 3.0]  [Reference Citation Analysis (0)]
54.  Levicar N, Pai M, Habib NA, Tait P, Jiao LR, Marley SB, Davis J, Dazzi F, Smadja C, Jensen SL. Long-term clinical results of autologous infusion of mobilized adult bone marrow derived CD34+ cells in patients with chronic liver disease. Cell Prolif. 2008;41 Suppl 1:115-125.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 40]  [Cited by in F6Publishing: 62]  [Article Influence: 3.9]  [Reference Citation Analysis (0)]
55.  Mohamadnejad M, Namiri M, Bagheri M, Hashemi SM, Ghanaati H, Zare Mehrjardi N, Kazemi Ashtiani S, Malekzadeh R, Baharvand H. Phase 1 human trial of autologous bone marrow-hematopoietic stem cell transplantation in patients with decompensated cirrhosis. World J Gastroenterol. 2007;13:3359-3363.  [PubMed]  [DOI]  [Cited in This Article: ]
56.  Kim JK, Park YN, Kim JS, Park MS, Paik YH, Seok JY, Chung YE, Kim HO, Kim KS, Ahn SH. Autologous bone marrow infusion activates the progenitor cell compartment in patients with advanced liver cirrhosis. Cell Transplant. 2010;19:1237-1246.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 62]  [Cited by in F6Publishing: 69]  [Article Influence: 4.9]  [Reference Citation Analysis (0)]
57.  Mohamadnejad M, Alimoghaddam K, Bagheri M, Ashrafi M, Abdollahzadeh L, Akhlaghpoor S, Bashtar M, Ghavamzadeh A, Malekzadeh R. Randomized placebo-controlled trial of mesenchymal stem cell transplantation in decompensated cirrhosis. Liver Int. 2013;33:1490-1496.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 108]  [Cited by in F6Publishing: 114]  [Article Influence: 10.4]  [Reference Citation Analysis (0)]
58.  Nikeghbalian S, Pournasr B, Aghdami N, Rasekhi A, Geramizadeh B, Hosseini Asl SM, Ramzi M, Kakaei F, Namiri M, Malekzadeh R. Autologous transplantation of bone marrow-derived mononuclear and CD133(+) cells in patients with decompensated cirrhosis. Arch Iran Med. 2011;14:12-17.  [PubMed]  [DOI]  [Cited in This Article: ]
59.  Jang YO, Kim YJ, Baik SK, Kim MY, Eom YW, Cho MY, Park HJ, Park SY, Kim BR, Kim JW. Histological improvement following administration of autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: a pilot study. Liver Int. 2014;34:33-41.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 126]  [Cited by in F6Publishing: 136]  [Article Influence: 13.6]  [Reference Citation Analysis (0)]
60.  Kim SU, Oh HJ, Wanless IR, Lee S, Han KH, Park YN. The Laennec staging system for histological sub-classification of cirrhosis is useful for stratification of prognosis in patients with liver cirrhosis. J Hepatol. 2012;57:556-563.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 99]  [Cited by in F6Publishing: 102]  [Article Influence: 8.5]  [Reference Citation Analysis (0)]
61.  Peng L, Xie DY, Lin BL, Liu J, Zhu HP, Xie C, Zheng YB, Gao ZL. Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: short-term and long-term outcomes. Hepatology. 2011;54:820-828.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 251]  [Cited by in F6Publishing: 259]  [Article Influence: 19.9]  [Reference Citation Analysis (0)]
62.  Lyra AC, Soares MB, da Silva LF, Braga EL, Oliveira SA, Fortes MF, Silva AG, Brustolim D, Genser B, Dos Santos RR. Infusion of autologous bone marrow mononuclear cells through hepatic artery results in a short-term improvement of liver function in patients with chronic liver disease: a pilot randomized controlled study. Eur J Gastroenterol Hepatol. 2010;22:33-42.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 81]  [Cited by in F6Publishing: 84]  [Article Influence: 6.0]  [Reference Citation Analysis (1)]
63.  Pai M, Zacharoulis D, Milicevic MN, Helmy S, Jiao LR, Levicar N, Tait P, Scott M, Marley SB, Jestice K. Autologous infusion of expanded mobilized adult bone marrow-derived CD34+ cells into patients with alcoholic liver cirrhosis. Am J Gastroenterol. 2008;103:1952-1958.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 164]  [Cited by in F6Publishing: 149]  [Article Influence: 9.3]  [Reference Citation Analysis (0)]
64.  Amin MA, Sabry D, Rashed LA, Aref WM, el-Ghobary MA, Farhan MS, Fouad HA, Youssef YA. Short-term evaluation of autologous transplantation of bone marrow-derived mesenchymal stem cells in patients with cirrhosis: Egyptian study. Clin Transplant. 2013;27:607-612.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 60]  [Cited by in F6Publishing: 59]  [Article Influence: 5.9]  [Reference Citation Analysis (0)]
65.  El-Ansary M, Abdel-Aziz I, Mogawer S, Abdel-Hamid S, Hammam O, Teaema S, Wahdan M. Phase II trial: undifferentiated versus differentiated autologous mesenchymal stem cells transplantation in Egyptian patients with HCV induced liver cirrhosis. Stem Cell Rev. 2012;8:972-981.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 115]  [Cited by in F6Publishing: 113]  [Article Influence: 9.4]  [Reference Citation Analysis (0)]
66.  Salama H, Zekri AR, Bahnassy AA, Medhat E, Halim HA, Ahmed OS, Mohamed G, Al Alim SA, Sherif GM. Autologous CD34+ and CD133+ stem cells transplantation in patients with end stage liver disease. World J Gastroenterol. 2010;16:5297-5305.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 60]  [Cited by in F6Publishing: 58]  [Article Influence: 4.1]  [Reference Citation Analysis (0)]
67.  Kharaziha P, Hellström PM, Noorinayer B, Farzaneh F, Aghajani K, Jafari F, Telkabadi M, Atashi A, Honardoost M, Zali MR. Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I-II clinical trial. Eur J Gastroenterol Hepatol. 2009;21:1199-1205.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 317]  [Cited by in F6Publishing: 307]  [Article Influence: 20.5]  [Reference Citation Analysis (0)]
68.  Salama H, Zekri AR, Ahmed R, Medhat I, Abdallah ES, Darwish T, Ahmed OS, Bahnassy A. Assessment of health-related quality of life in patients receiving stem cell therapy for end-stage liver disease: an Egyptian study. Stem Cell Res Ther. 2012;3:49.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 8]  [Article Influence: 0.7]  [Reference Citation Analysis (0)]
69.  Park CH, Bae SH, Kim HY, Kim JK, Jung ES, Chun HJ, Song MJ, Lee SE, Cho SG, Lee JW. A pilot study of autologous CD34-depleted bone marrow mononuclear cell transplantation via the hepatic artery in five patients with liver failure. Cytotherapy. 2013;15:1571-1579.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 16]  [Cited by in F6Publishing: 19]  [Article Influence: 1.7]  [Reference Citation Analysis (0)]
70.  Lyra AC, Soares MB, da Silva LF, Fortes MF, Silva AG, Mota AC, Oliveira SA, Braga EL, de Carvalho WA, Genser B. Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease. World J Gastroenterol. 2007;13:1067-1073.  [PubMed]  [DOI]  [Cited in This Article: ]