Randomized placebo‐controlled trial of mesenchymal stem cell transplantation in decompensated cirrhosis

Mohamadnejad, Mehdi; Alimoghaddam, Kamran; Bagheri, Mohammad; Ashrafi, Mandana; Abdollahzadeh, Leila; Akhlaghpoor, Shahram; Bashtar, Maryam; Ghavamzadeh, Ardeshir; Malekzadeh, Reza

doi:10.1111/liv.12228

Cited by 146 publications

(147 citation statements)

References 31 publications

(52 reference statements)

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“…In the field of liver cirrhosis, as shown in Table 1, many autologous [70][71][72][73][74][75][76][77][78][79][80][81][82][83] and four allogeneic [59][60][61][62] MSC therapies involving a variety of tissue origins and administration routes have been reported. Although details regarding the mechanisms of therapeutic effects in humans remain unclear, most studies have reported favorable effects with improvement in MELD scores, Child-Pugh scores, and some serum markers such as albumin and bilirubin.…”

Section: Mscsmentioning

confidence: 99%

Status of and candidates for cell therapy in liver cirrhosis: overcoming the “point of no return” in advanced liver cirrhosis

Terai

Tsuchiya

2016

J Gastroenterol

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The treatment of liver cirrhosis is currently being standardized and developed specifically to reduce activation of hepatic stellate cells (HSCs), inhibit fibrosis, increase degradation of matrix components, and reduce activated myofibroblasts. Cell therapy can be applied in the treatment of liver cirrhosis; however, the characteristic features of this therapy differ from those of other treatments because of the involvement of a living body origin and production of multiple cytokines, chemokines, matrix metalloproteinases (MMPs), and growth factors. Thus, cell therapies can potentially have multiple effects on the damaged liver, including alleviating liver cirrhosis and stimulating liver regeneration with affecting the host cells. Cell therapies initially involved autologous bone marrow cell infusion, and have recently developed to include the use of specific cells such as mesenchymal stem cells and macrophages. The associated molecular mechanisms, routes of administration, possibility of allogeneic cell therapy, and host conditions appropriate for cell therapies are now being extensively analyzed. In this review, we summarize the status and future prospects of cell therapy for liver cirrhosis.

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Section: Mscsmentioning

confidence: 99%

Status of and candidates for cell therapy in liver cirrhosis: overcoming the “point of no return” in advanced liver cirrhosis

Terai

Tsuchiya

2016

J Gastroenterol

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“…Patient serum bilirubin levels only began to increase 18 months after the infusion. This clinical In contrast, a randomized control study showed that ex vivo expanded BM-MSCs did not significantly improve the average liver function of 27 decompensated cirrhosis patients [9]. These patients were transfused with a median dose of 1.95 × 10 8 ex vivo expanded BM-MSCs via a peripheral vein and were followed up for 12 months.…”

Section: Bone Marrow-derived Mesenchymal Stem Cells (Bm-mscs) In Automentioning

confidence: 86%

“…The therapeutic utility of BM-MNC has been largely evaluated in liver cirrhosis patients associated with hepatitis B, hepatitis C, alcoholic liver diseases, and decompensated and biliary duct liver cirrhosis. ChildPugh Score (CPS) and Model for End-Stage Liver Disease (MELD) are the two important scoring systems widely used to evaluate the prognosis of patients with liver diseases [9,10], including cirrhosis. The CPS considers five clinical factors, three of which assess the synthetic function of the liver (i.e., total bilirubin level, serum albumin level and international normalized ratio, or INR) and 2 of which are based on clinical assessments (i.e., degree of ascites and hepatic encephalopathy).…”

Section: Bone Marrow-derived Mononuclear Cells (Bmmncs) In Autologousmentioning

confidence: 99%

“…Specifically, cell-based therapies for liver cirrhosis have successfully progressed from preliminary laboratory and pre-clinical evaluations. Several studies have demonstrated that residential and non-residential liver stem cells have the ability to differentiate into hepatocyte-like cells or bile duct epithelial cells, and more pertinently restore liver function [7][8][9][10][11]. The mechanistic action of stem cell-mediated restoration of liver function in liver cirrhosis has not been fully defined.…”

Section: Introductionmentioning

confidence: 99%

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Adult Stem Cell Therapy in Liver Cirrhosis Management: Current Practices and Future Perspectives

Subbanna¹,

Radha²,

Choy³

et al. 2017

Int J Stem Cell Res Ther

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“…[4][5][6] However, in vitro over expansion to provide enough number of cells, and cryopreservation to meet the need of ready to use cells might compromise cell quality. A review on the failure of phase III clinical trial, which used over expanded cryopreserved mesenchymal stem cells to cure steroid resistant graft versus host disease, supposed that the failure was due to impaired immunomodulatory functions due to cryopreservation, and senescence due to overexpansion.…”

Section: Introductionmentioning

confidence: 99%

Effect of Cryopreservation and cumulative population doublings on Senescence of Umbilical Cord Mesenchymal Stem Cells

Pawitan¹,

Goei²,

Liem³

et al. 2017

IJPTR

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: Background: Multiple harvest explant method (MHEM) derived umbilical cord mesenchymal stem cells (UC-MSCs) was shown to undergo senescent beginning at passage-10 (P-10). However, for the same cells, there are no senescent data after cryopreservation and passage. Therefore, this study aimed to analyze the senescent profile of cryopreserved MHEM derived UC-MSCs after serial passages. Methods: MHEM derived UC-MSCs were isolated and cultured in platelet lysate (PL) containing medium as described previously. The cells were cryopreserved at passage-1 (P-1) in 10% dimethyl sulfoxide (DMSO) and 10% PL containing alpha minimal essential medium (αMEM). Cell density at cryopreservation was 500 000 cells/mL. After one month, the cells were thawed and recultured until P-8 in six 12-well plate. At 80-90% confluent, two wells were harvested and the cells were recultured into six wells, and the four remaining wells were subjected to senescent (β-galactosidase) staining, which was done for all passages. Random photographs were taken from all stained wells, and senescent percentage was recorded. Results: No senescent cells were observed at P-2. Senescent cells began to appear at P-3. Percentage (mean ± SD) of senescent cells from P-3 through P-8 were 0.04 ± 0.02, 1.18 ± 1.82, 0.14 ± 0.18, 0.49 ± 0.00, 0.58 ±0.91, and 0.07 ± 0.07, respectively. Results: No senescent cells were observed at P-2. Senescent cells began to appear at P-3. Percentage (mean ± SD) of senescent cells from P-3 through P-8 were 0.04 ± 0.02, 1.18 ± 1.82, 0.14 ± 0.18, 0.49 ± 0.00, 0.58 ±0.91, and 0.07 ± 0.07, respectively. Conclusion: No senescent cells were observed at P-2 (cumulative population doubling [CPD] > 9.38). Senescent cells began to appear at P-3 (CPD > 14.06), but in all passages until P-8 (CPD >34.34) the senescent percentage was below 5%.

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Randomized placebo‐controlled trial of mesenchymal stem cell transplantation in decompensated cirrhosis

Cited by 146 publications

References 31 publications

Status of and candidates for cell therapy in liver cirrhosis: overcoming the “point of no return” in advanced liver cirrhosis

Status of and candidates for cell therapy in liver cirrhosis: overcoming the “point of no return” in advanced liver cirrhosis

Adult Stem Cell Therapy in Liver Cirrhosis Management: Current Practices and Future Perspectives

Effect of Cryopreservation and cumulative population doublings on Senescence of Umbilical Cord Mesenchymal Stem Cells

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