GMP-Grade Human Fetal Liver-Derived Mesenchymal Stem Cells for Clinical Transplantation

Larijani, Bagher; Aghayan, Hamid Reza; Goodarzi, Parisa; Arjmand, Babak

doi:10.1007/7651_2014_101

Cited by 23 publications

(12 citation statements)

References 26 publications

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“…Different cell sources (cell lines, stem cells, progenitor cells, and other non-parenchymal cell types) have therefore been proposed as alternative therapeutic liver cell products (4). By expressing both hepatic and mesenchymal markers, liver mesenchymal-like cells have been reported as a potential reservoir of hepatocytes (6)(7)(8)(9)(10). When exposed to in vitro hepatogenic differentiation (HD), adult-derived human liver stem/progenitor cells (ADHLSCs) may differentiate into hepatocyte-like cells, thus acquiring liver metabolic functions (11).…”

Section: Original Articlementioning

confidence: 99%

Cytokinome of adult-derived human liver stem/progenitor cells: immunological and inflammatory features

Najar¹,

Crompot²,

Raicevic³

et al. 2018

Hepatobiliary Surg. Nutr

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Background: Being non-immunogenic and capable of achieving major metabolic liver functions, adultderived human liver stem/progenitor cells (ADHLSCs) are of special interest in the field of liver cell therapy. The cytokine repertoire of engrafted cells may have critical impacts on the immune response balance, particularly during cell transplantation. Methods: In this work, we analyzed the cytokinome of ADHLSCs during hepatogenic differentiation (HD) following stimulation with a mixture of inflammatory cytokines (I) in vitro and compared it to that of mature hepatocytes. Results: Independent of their hepatic state, ADHLSCs showed no constitutive expression of proinflammatory cytokines, which were significantly induced by inflammation (IL-1β, IL-6, IL-8, TNFα, CCL5, IL-12a, IL-12b, IL-23p19, IL-27p28 and EBI-3). IL1-RA and IDO-1, as immunoregulatory cytokines, were highly induced in undifferentiated ADHLSCs, whereas TGF-β was downregulated by both hepatic and inflammatory events. Interestingly, TDO-1 was exclusively expressed in ADHLSCs after hepatic differentiation and enhanced by inflammatory cytokines. Compared to mature hepatocytes, hepaticdifferentiated ADHLSCs showed significantly different cytokine expression patterns. Conclusions: By establishing the cytokinome of ADHLSCs and highlighting their immunological and inflammatory features, we can enhance our knowledge about the safety and efficiency of the transplantation strategy.

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Section: Original Articlementioning

confidence: 99%

Cytokinome of adult-derived human liver stem/progenitor cells: immunological and inflammatory features

Najar¹,

Crompot²,

Raicevic³

et al. 2018

Hepatobiliary Surg. Nutr

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“…LHMSCs were first isolated from first-trimester fetal livers [ 16 ] and later from second-trimester fetal livers [ 17 ]. To ensure the safety, quality, and identity of cell products, a standardized procedure in compliance with current Good Manufacturing Practices has been formulated [ 18 ]. Briefly, disrupted liver tissue is harvested using a homogenizer following removal of adjacent tissues.…”

Section: Isolation and Culture Of Lhmscsmentioning

confidence: 99%

Liver-derived human mesenchymal stem cells: a novel therapeutic source for liver diseases

Wang

Chen

et al. 2016

Stem Cell Res Ther

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Mesenchymal stem cells (MSCs) represent an attractive cell type for research and therapy due to their ability to proliferate, differentiate, modulate immune reactions, and secrete trophic factors. MSCs exist in a multitude of tissues, including bone marrow, umbilical cord, and adipose tissues. Moreover, MSCs have recently been isolated from the liver. Compared with other MSC types, liver-derived human MSCs (LHMSCs) possess general morphologies, immune functions, and differentiation capacities. Interestingly, LHMCSs produce higher levels of pro-angiogenic, anti-inflammatory, and anti-apoptotic cytokines than those of bone marrow-derived MSCs. Thus, these cells may be a promising therapeutic source for liver diseases. This paper summarizes the biological characteristics of LHMSCs and their potential benefits and risks for the treatment of liver diseases.

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“…When there is no alternative to research-grade reagents, the animal origin could be used if the manufacturer officially confirms their compliance with GMP regulations. We previously reported the clinicalgrade cultivation and banking of human Schwann cells, human fetal liver-derived mesenchymal stem cells, and human adipose tissue-derived mesenchymal stem cells (19,35,36). In the current study, in order for clinical-grade fibroblasts establishment, according to the Stringent Ethical guidelines, informed consent was obtained from the donor.…”

Section: Discussionmentioning

confidence: 99%

GMP-Compliant Human Fetal Skin Fibroblasts for Wound Healing

et al. 2018

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Background: Among different kinds of cells involved in the wound healing process, fibroblasts play a pivotal role in the proliferation phase of this procedure wherein they induce the production of local growth factors and cytokines. Fetal fibroblasts with low immunogenic property and different wound healing process could be considered as a suitable alternative to neonatal foreskin cell based products in regenerative medicine and cell therapy. Cell therapy is an almost newly introduced method in the medical field and is also a challenging issue, which should assure the safety of the final product and the absence of viral or bacterial contamination with minimal immunogenic response. Therefore, based on current GMP (cGMP) principles, it is a matter of great importance to monitor raw materials' quality and the conformity of all production procedures including cell culture, collection, and cryopreservation with validated standard operating procedures (SOPs). In the current study, we demonstrated the GMP-compatible and clinical-grade fetal fibroblast cells banking to be used for clinical applications. Methods: All steps of isolation and culturing and cryopreservation of fetal fibroblast cells were performed under the sterile condition according to cGMP guidelines in the clean room. During the cell culture procedures, bacteriological investigation was performed in order to identify the probable contamination of the samples.

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GMP-Grade Human Fetal Liver-Derived Mesenchymal Stem Cells for Clinical Transplantation

Cited by 23 publications

References 26 publications

Cytokinome of adult-derived human liver stem/progenitor cells: immunological and inflammatory features

Cytokinome of adult-derived human liver stem/progenitor cells: immunological and inflammatory features

Liver-derived human mesenchymal stem cells: a novel therapeutic source for liver diseases

GMP-Compliant Human Fetal Skin Fibroblasts for Wound Healing

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