Infusion of human umbilical cord-derived mesenchymal stem cells effectively relieves liver cirrhosis in DEN-induced rats

Hong, Jingxin; Jin, Haixia; Han, Jianming; Hu, Huanzhang; Liu, Jian; Li, Linfang; Huang, Yao Qi; Wang, Dandan; Wu, Mengchao; Qiu, Lugui; Qian, Qijun

doi:10.3892/mmr.2014.1927

Cited by 23 publications

(21 citation statements)

References 27 publications

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“…Nevertheless, researchers have investigated the effects of total MSC dose and dose splitting to determine an optimal therapeutic window. Hong et al (77) transplanted hUC-MSCs into rats with DMN-induced liver injury (0.01% supplemented diet given ad libitum for 4 wk) at varied doses, either as single infusions or as split dosing. They found that the antifibrotic effect was dose dependent, but probably not enhanced by split infusions (77).…”

Section: Does the Dose Of Mscs Matter?mentioning

confidence: 99%

Mesenchymal stromal cells and liver fibrosis: a complicated relationship

et al. 2016

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Mesenchymal stromal cell (MSC) therapy demands the attention of clinicians and scientists because of its potential in clinical fields that are bereft of medical options, but also because of the controversies that underlie its mode of action. MSCs are potent immune modulators, yet their biologic activity may not be innate, requiring licensing by their microenvironment. This property has prompted researchers to explore unique ways in which MSCs may be able to exert distinct biologic effects in different pathologic settings. More than 400 clinical trials have investigated the therapeutic capacity of MSCs in different pathologies, including liver disease. Along with their anti-inflammatory action, there are data to suggest that MSCs may exert direct antifibrotic effects, although enthusiasm for their use in patients has been tempered by concerns of a possible profibrotic role of endogenous MSCs in response to injury. There is a significant need for antifibrotic therapy to combat the increasing burden of patients with cirrhosis, and a concerted effort is required to determine the mechanisms by which MSCs modulate the liver's response to injury, both endogenously and after adoptive transfer. This review critically appraises the preclinical published data with regard to the capacity of MSCs to influence fibrotic response to liver injury and will explore the potential mechanisms that underpin the reported beneficial effects of MSC therapy in the context of liver injury and fibrosis.-Haldar, D., Henderson, N. C., Hirschfield, G., Newsome, P. N. Mesenchymal stromal cells and liver fibrosis: a complicated relationship.

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Section: Does the Dose Of Mscs Matter?mentioning

confidence: 99%

Mesenchymal stromal cells and liver fibrosis: a complicated relationship

et al. 2016

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“…The latter zona pellucida glycoprotein is only expressed in oocytes (Lefièvre et al., ). Earlier studies reported ZP‐like structures surrounding OLCs differentiated in vitro (Hong et al., ). Singhal et al.…”

Section: Discussionmentioning

confidence: 92%

“…Hong et al. () reported that human follicular fluid stimulated differentiation into OLCs in vitro from stem cells. However, the differentiation of OLCs from ovarian stem cells isolated from adult bovine ovaries has not yet been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Bovine ovarian stem cells differentiate into germ cells and oocyte‐like structures after culture in vitro

Souza

Costa

Cunha

et al. 2016

Reprod Domestic Animals

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Stem cells have been isolated from ovaries, and their ability to differentiate into oocytes in vitro has been demonstrated for mice and human, but not for bovine species. The aims of this study were to isolate germline stem cells from bovine ovaries and to evaluate the effects of bone morphogenetic proteins (BMPs) 2 and 4, and follicular fluid on the differentiation of these stem cells into oocyte-like structures. The ovarian stem cells were isolated and cultured in α-MEM supplemented with BMP2, BMP4 or follicular fluid. On days 0 and 14, cells were evaluated for their morphological appearance, viability, expression of alkaline phosphatase and for markers of germ cell formation (VASA and DAZL) and oocyte development (GDF9, ZPA and SCP3) by qPCR. Levels of mRNA were analysed using ANOVA and Bonferroni test (p < .05). The results showed that at day 0, ovarian stem cells expressed specific markers of pluripotency (OCT4, SOX). In addition, these cells were positive for alkaline phosphatase, which is a marker commonly used to identify primordial germ cells (PGCs). After the period of differentiation, cells had morphological features that resemble PGCs and oocyte-like cells (OLCs). An increase, ranging from five to 14 times, in the expression of VASA was observed in cells cultured in medium supplemented with BMPs and follicular fluid, while the increase in DAZL expression ranged from four to six times. In addition, OLCs had an increase in expression of mRNAs for GDF9, ZPA and SCP3 that ranged from two to eight times. In conclusion, OLCs can be differentiated in vitro from ovarian stem cells and BMPs and follicular fluid are effective in stimulating the expression of mRNAs for germ cell and oocyte markers.

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“…With respect to the involvement of MSCs in liver regenerative medicine, many studies have demonstrated that the infusion of human umbilical cord-or cord blood-derived MSCs via a vein or multiple direct injections into the liver effectively relieves liver cirrhosis and improves the survival rate in rodent models. These studies also suggest that multiple infusions show better clinical outcomes as compared to a single infusion of allogeneic MSCs [62][63][64][65].…”

Section: Allogeneic Stem Cells In Liver Cirrhosis Therapymentioning

confidence: 87%