Curative effect of hepatic portal venous administration of autologous bone marrow in AIDS patients with decompensated liver cirrhosis

Liu, B; Chen, X; Wang, Y; Shi, Yufang

doi:10.1038/cddis.2013.261

Cited by 8 publications

(13 citation statements)

References 7 publications

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“… 2 Other studies have focused on directing regeneration of functional hepatocytes, and cellular therapies of chronic liver disease have begun to be tested. 3 In human clinical trials, ABM infusion in late-stage cirrhotic patients resulted in marked improvements in hepatic function, 4 similar to those seen in the patients studied by Liu et al 1 here, and splenectomy similarly markedly enhanced the effects of ABM infusion. 5 ABM infusion was effective in both virally and non-virally caused cirrhosis, suggesting that antiviral activity is not the responsible mechanism.…”

supporting

confidence: 79%

“… Schematic representation of the results of Liu et al 1 showing that intrahepatic infusion of ABM resulted in enhanced liver function and sustained CD4 + cell increases in patients with liver cirrhosis and AIDS …”

Section: Figurementioning

confidence: 99%

“…The most striking aspect of the Liu et al 1 paper was the persistent increase in CD4 + T cells following ABM infusion in these AIDS patients with cirrhosis. Stable reconstitution of CD4 + T-cell number and function, with complete suppression of viral replication and elimination of viral reservoirs, has been the ‘holy grail' of AIDS therapy.…”

mentioning

confidence: 93%

“…Issues regarding route of administration of BM cells also need to be addressed. This study by Liu et al 1 clearly offers a novel window into the critical goal of true reconstitution of immune response in patients with AIDS, and as such is provocative and noteworthy.…”

mentioning

confidence: 93%

“…In a recent Cell Death and Disease article, Liu et al 1 reported a striking observation that portal vein infusion of autologous bone marrow (ABM) in four AIDS patients with severe liver cirrhosis resulted not only in significant clinical improvement of liver function but also a sustained enhancement of CD4 + T-cell levels, as shown schematically in Figure 1 . These results raise the important possibility that ABM infusion, in context of concurrent liver disease, can result in CD4 + T-cell reconstitution in AIDS patients.…”

mentioning

confidence: 99%

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Bringing back the help: autologous bone marrow infusion restores CD4+ T cells in AIDS patients with chronic liver disease

Rabson

2013

Cell Death Dis

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supporting

confidence: 79%

Section: Figurementioning

confidence: 99%

mentioning

confidence: 93%

mentioning

confidence: 93%

mentioning

confidence: 99%

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Bringing back the help: autologous bone marrow infusion restores CD4+ T cells in AIDS patients with chronic liver disease

Rabson

2013

Cell Death Dis

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Fibrotic liver microenvironment promotes Dll4 and SDF-1-dependent T-cell lineage development

et al. 2019

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The reconstitution of the T-cell repertoire and quantity is a major challenge in the clinical management of HIV infection/AIDS, cancer, and aging-associated diseases. We previously showed that autologous bone marrow transfusion (BMT) via the hepatic portal vein could effectively restore CD4 + T-cell count in AIDS patients also suffering from decompensated liver cirrhosis. In the current study, we characterized T-cell reconstitution in a mouse model of liver fibrosis induced by CCl 4 and found that T-cell reconstitution after BMT via hepatic portal vein was also greatly enhanced. The expression of Dll4 (Delta-like 4), which plays an important role in T-cell progenitor expansion, was elevated in hepatocytes of fibrotic livers when compared to normal livers. This upregulation of Dll4 expression was found to be induced by TNFα in an NFκB-dependent manner. Liver fibroblasts transfected with Dll4 (LF-Dll4) also gained the capacity to promote T-cell lineage development from hematopoietic stem cells (HSCs), resulting in the generation of DN2 (CD4 and CD8 DN 2) and DN3 T-cell progenitors in vitro, which underwent a normal maturation program when adoptively transferred into Rag-2 deficient hosts. We also demonstrated a pivotal role of SDF-1 produced by primary liver fibroblasts (primary LF) in T-lineage differentiation from HSCs. These results suggest that Dll4 and SDF-1 in fibrotic liver microenvironment could promote extrathymic T-cell lineage development. These results expand our knowledge of T-cell development and reconstitution under pathological conditions.

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Autologous bone marrow cell transplantation in the treatment of HIV patients with compensated cirrhosis

et al. 2020

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Liver stem cell therapy is a promising tool to improve decompensated liver cirrhosis (DLC). Especially in patients infected with human immunodeficiency virus (HIV), the condition of the liver may be aggravated by antiretroviral therapy. A total of 21 patients diagnosed with DLC and HIV infection were divided into two groups as follows: those who received (combination therapy group, 14 patients) and those who did not receive (routine therapy group, 7 patients) bone marrow cell transplantation through the portal vein. Two patients died of surgery-related complications in the combination therapy group. The results showed that the survival rate was 85.7% in the combination therapy group after 2 years of follow-up, which was significantly higher than the 14.3% in the conventional therapy group (P<0.01). After treatment, the liver function score decreased significantly in the combination therapy group at 1 (t = 4.276, P = 0.000), 3 (t = 9.153, P = 0.000), and 12 (t = 13.536, P = 0.000) months, the levels of albumin were significantly increased, and the total bilirubin level and prothrombin time were significantly reduced or shortened as compared with the routine therapy group (P<0.05 or <0.01). The white blood cell count, hemoglobin, platelet count, and CD4+ and CD8+ levels were significantly higher in the combination therapy group at different time points as compared with the routine therapy group (P<0.05 or <0.01). In summary, the combination therapy is effective in HIV-infected patients with DLC and useful for the recovery of liver function and cellular immune function but may increase the risk of severe complications after surgery.

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Curative effect of hepatic portal venous administration of autologous bone marrow in AIDS patients with decompensated liver cirrhosis

Cited by 8 publications

References 7 publications

Bringing back the help: autologous bone marrow infusion restores CD4+ T cells in AIDS patients with chronic liver disease

Bringing back the help: autologous bone marrow infusion restores CD4+ T cells in AIDS patients with chronic liver disease

Fibrotic liver microenvironment promotes Dll4 and SDF-1-dependent T-cell lineage development

Autologous bone marrow cell transplantation in the treatment of HIV patients with compensated cirrhosis

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