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

Lyra, André Castro; Soares, Milena Botelho Pereira; Silva, Luiz Flavio Maia da; Oliveira, Sheilla Andrade de; Fortes, Filomeno; Silva, André Goyanna Pinheiro; Brustolim, Daniele; Genser, Bernd; Santos, Ricardo Ribeiro dos; Lyra, Luiz Guilherme Costa

doi:10.1097/meg.0b013e32832eb69a

Cited by 100 publications

(62 citation statements)

References 24 publications

(33 reference statements)

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“…Lyra et al in Brazil also reported the feasibility and safety of autologous bone marrow cell infusion through not a peripheral vein but a hepatic artery for chronic liver disease patients waiting liver transplantation (19,20). Moreover, Kharaziha et al showed liver function improvements after administration of autologous mesenchymal stem cells (21).…”

Section: Discussionmentioning

confidence: 99%

Novel Findings for the Development of Drug Therapy for Various Liver Diseases: Current State and Future Prospects for Our Liver Regeneration Therapy Using Autologous Bone Marrow Cells for Decompensated Liver Cirrhosis Patients

2011

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Abstract.We have developed an in vivo mouse model [the green fluorescent protein (GFP) / carbon tetrachloride (CCl 4 ) model] and reported that infused GFP-positive bone marrow cells administered via a tail vein efficiently repopulated cirrhotic liver tissue under conditions of persistent liver damage induced by CCl 4 . Moreover, bone marrow cells infused into the liver improved liver function and ameliorated liver fibrosis with higher expression of matrix metalloproteinase 9 (MMP-9), consistent with improved survival rate. Based on these findings, we started a multicenter clinical trial of autologous bone marrow cell infusion (ABMi) therapy for decompensated liver cirrhosis patients and demonstrated the efficacy of this approach without unexpected complications. However, this therapy involves bone marrow aspiration under general anesthesia and is not indicated for patients for whom general anesthesia is difficult. We therefore aimed to develop a new liver regeneration therapy in which cells having a curative effect on liver cirrhosis are isolated and cultured from a small amount of autologous bone marrow aspirated under local anesthesia and infused back into the same subject. Herein, we present results for the GFP/CCl 4 model and ABMi therapy and future prospects for a new liver regeneration therapy.

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Section: Discussionmentioning

confidence: 99%

Novel Findings for the Development of Drug Therapy for Various Liver Diseases: Current State and Future Prospects for Our Liver Regeneration Therapy Using Autologous Bone Marrow Cells for Decompensated Liver Cirrhosis Patients

2011

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“…One patient died of sepsis, and one patient had development of hepatorenal syndrome that led to discontinuation of the trial. 64 Three of the studies were randomized controlled trials, 2 of which revealed efficacy 61,62 and one that did not. 63 …”

Section: Clinical Trials With Autologous Bone Marrow–derived Stem Cellsmentioning

confidence: 99%

Cellular Therapy for Liver Disease

Huebert

Rakela

2014

Mayo Clinic Proceedings

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Regenerative medicine is energizing and empowering basic science and has the potential to dramatically transform health care in the future. Given the remarkable intrinsic regenerative properties of the liver, as well as widespread adoption of regenerative strategies for liver disease (eg, liver transplant, partial hepatectomy, living donor transplant), hepatology has always been at the forefront of clinical regenerative medicine. However, an expanding pool of patients awaiting liver transplant, a limited pool of donor organs, and finite applicability of the current surgical approaches have created a need for more refined and widely available regenerative medicine strategies. Although cell-based therapies have been used extensively for hematologic malignant diseases and other conditions, the potential application of cellular therapy for acute and chronic liver diseases has only more recently been explored. New understanding of the mechanisms of liver regeneration and repair, including activation of local stem/progenitor cells and contributions from circulating bone marrow–derived stem cells, provide the theoretical underpinnings for the rational use of cell-based therapies in clinical trials. In this review, we dissect the scientific rationale for various modalities of cell therapy for liver diseases being explored in animal models and review those tested in human clinical trials. We also attempt to clarify some of the important ongoing questions that need to be addressed in order to bring these powerful therapies to clinical translation. Discussions will cover transplant of hepatocytes and liver stem/progenitor cells as well as infusion or stimulation of bone marrow–derived stem cells. We also highlight tremendous scientific advances on the horizon, including the potential use of induced pluripotent stem cells and their derivatives as individualized regenerative therapy for liver disease.

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“…These two initial studies highlight the significant number of variables involved in comparing these and subsequent studies. Further small-scale, uncontrolled studies have included variation in the patients enrolled (aetiology and severity of liver disease), the method of cell harvest (direct BM aspiration or peripheral blood leukopheresis), the type and number of cells infused (various populations from unsorted mononuclear cells to purified CD133+ HSC) and the route of cell infusion (hepatic artery, portal vein or peripheral vein) [65,66,67,68,69,70]. The aim of many of these studies was to determine safety and feasibility and in that sense the outcomes were promising; however, the size and nature of many of these subsequent studies meant that meaningful conclusions on clinical outcomes could not be made.…”

Section: Clinical Studiesmentioning

confidence: 99%

“…In more recent small controlled trials, Lyra et al [66] demonstrated significant improvements in liver function 1 year following infusion of BM mononuclear cells into the hepatic artery when compared with untreated control patients. Ismail et al [71] examined the role of infusion of BM mononuclear cells prior to liver resection in cirrhotic patients with hepatocellular carcinoma and showed improved outcomes 3 months post-operatively compared with patients undergoing resection alone.…”

Section: Clinical Studiesmentioning

confidence: 99%

Bone Marrow Stem Cell Therapy for Liver Disease

King¹,

Newsome²

2014

Dig Dis

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Liver disease is a rising cause of mortality and morbidity, and treatment options remain limited. Liver transplantation is curative but limited by donor organ availability, operative risk and long-term complications. The contribution of bone marrow (BM)-derived stem cells to tissue regeneration has been recognised and there is considerable interest in the potential benefits of BM stem cells in patients with liver disease. In chronic liver disease, deposition of fibrous scar tissue inhibits hepatocyte proliferation and leads to portal hypertension. Although initial reports had suggested transdifferentiation of stem cells into hepatocytes, the beneficial effects of BM stem cells are more likely derived from the ability to breakdown scar tissue and stimulate hepatocyte proliferation. Studies in animal models have yielded promising results, although the exact mechanisms and cell type responsible have yet to be determined. Small-scale clinical studies have quickly followed and, although primarily designed to examine safety and feasibility of this approach, have reported improvements in liver function in treated patients. Well-designed, controlled studies are required to fully determine the benefits of BM stem cell therapy.

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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

Cited by 100 publications

References 24 publications

Novel Findings for the Development of Drug Therapy for Various Liver Diseases: Current State and Future Prospects for Our Liver Regeneration Therapy Using Autologous Bone Marrow Cells for Decompensated Liver Cirrhosis Patients

Novel Findings for the Development of Drug Therapy for Various Liver Diseases: Current State and Future Prospects for Our Liver Regeneration Therapy Using Autologous Bone Marrow Cells for Decompensated Liver Cirrhosis Patients

Cellular Therapy for Liver Disease

Bone Marrow Stem Cell Therapy for Liver Disease

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