Differentiation of Bone Marrow-derived Mesenchymal Stem Cells into Hepatocyte-like Cells on Nanofibers and Their Transplantation into a Carbon Tetrachloride-Induced Liver Fibrosis Model

Piryaei, Abbas; Valojerdi, Mojtaba Rezazadeh; Shahsavani, Mansoureh; Baharvand, Hossein

doi:10.1007/s12015-010-9126-5

Cited by 111 publications

(101 citation statements)

References 45 publications

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“…We have created our nano ECM from an electrospun nonwoven matrix of polyamide nanofibers with an average fiber diameter of 280 nm [33], which was employed as a model to mimic the geometry and nanotopography of the ECM/basement membrane for cell growth [10]. The beneficial influence of this nanofibrillar surface has been reported in cultures of different somatic cells [1,2,25,27] and the differentiation of human embryonic stem cells into a hepatic lineage as well as mouse mesenchymal stem cells [13,31]. Recently, we demonstrated enhanced migration, proliferation, and morphology of neural progenitors plated on this nano-structure in comparison with their maintenance on tissue-culture plates [32].…”

Section: Discussionmentioning

confidence: 99%

Behavior of mouse spermatogonial stem-like cells on an electrospun nanofibrillar matrix

Malek

Kohram

Shahverdi

et al. 2012

J Assist Reprod Genet

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Purpose Spermatogonial stem cells are affected by the interactions of extrinsic signals produced by components of the microenvironment niche, in addition to the chemical and physical properties of the extracellular matrix. Therefore, this study was initiated to assess the interaction of these cells on a synthetic nanofibrillar extracellular matrix that mimicked the geometry and nanotopography of the basement membrane for cellular growth. Methods This study has used a variety of experimental approaches to investigate the interaction of mouse neonatalderived spermatogonial stem-like cells on a synthetic random oriented three-dimensional nanofibrillar matrix composed of electrospun polyamide nanofibers (Ultra-Web™).Results Spermatogonial stem-like cell colonies were characterized by their ability to express α6-integrin, Thy-1, PLZF, and β1-integrin. After culture of cells on the nanofibrillar surfaces for 7 days, the number of colonies, the number of cells in each colony, and the average area of colonies were increased (P<0.05). However, the expression difference of related markers in both groups was not significant. A significantly higher proliferation and survival was observed in the nanofibrillar group (P<0.05). After transplantation into the testes of busulfan-treated adult mice, spermatogonial stem-like cell colonies that were cultured on the nanofibrillar surface demonstrated functionality, as verified by their ability to migrate to the seminiferous basal membrane, where they produced additional colonies. Conclusions These results have suggested that electrospun nanofibrillar surfaces could provide a more favorable microenvironment for in vitro short term culture of spermatogonial stem-like cell colonies.

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Section: Discussionmentioning

confidence: 99%

Behavior of mouse spermatogonial stem-like cells on an electrospun nanofibrillar matrix

Malek

Kohram

Shahverdi

et al. 2012

J Assist Reprod Genet

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“…There are many problems associated with this paradigm, particularly during the in vitro manipulation process and the delivery and local engraftment of re-transplantation cells [16]. Moreover, stem cell fate is influenced by a number of factors including extracellular matrices (ECMs) and interactions that require robust control for safe and effective regeneration of functional tissue [19]. Appearance of a novel field of science and technology called tissue engineering raises hope for the solution of the problems mentioned above [17].…”

Section: Introductionmentioning

confidence: 99%

Hepatic differentiation from human mesenchymal stem cells on a novel nanofiber scaffold

Ghaedi¹,

Soleimani

Shabani

et al. 2012

Cellular and Molecular Biology Letters

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Abstract:The emerging fields of tissue engineering and biomaterials have begun to provide potential treatment options for liver failure. The goal of the present study is to investigate the ability of a poly L-lactic acid (PLLA) nanofiber scaffold to support and enhance hepatic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs). A scaffold composed of poly L-lactic acid and collagen was fabricated by the electrospinning technique. After characterizing isolated hMSCs, they were seeded onto PLLA nanofiber scaffolds and induced to differentiate into a hepatocyte lineage. The mRNA levels and protein expression of several important hepatic genes were determined using RT-PCR, immunocytochemistry and ELISA. Flow cytometry revealed that the isolated bone marrow-derived stem cells were positive for hMSC-specific markers CD73, CD44, CD105 and CD166 and negative for hematopoietic markers CD34 and CD45. The differentiation of these stem cells into adipocytes and osteoblasts demonstrated their multipotency. Scanning electron microscopy showed adherence of cells in the nanofiber scaffold during differentiation towards hepatocytes. Our results showed that expression levels of liver-specific markers such as albumin, α-fetoprotein, and cytokeratins 8 and 18 were higher in differentiated cells on the nanofibers than when cultured on plates. Importantly, liver functioning serum proteins, albumin and α-1 antitrypsin were secreted into the culture medium at higher levels by the differentiated cells on the nanofibers than on the plates, demonstrating that our nanofibrous scaffolds promoted and enhanced hepatic differentiation under our culture conditions. Our results show that the engineered PLLA nanofibrous scaffold is a conducive matrix for the differentiation of MSCs into functional hepatocyte-like cells. This represents the first step for the use of this nanofibrous scaffold for culture and differentiation of stem cells that may be employed for tissue engineering and cell-based therapy applications.

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“…BMMSCs induced under specific conditions can differentiate into various tissues and cells in different micro-environments. A number of studies have demonstrated that, when cultured with epidermal growth factor (EGF), hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF) (Chivu et al 2009;Forte et al 2006;Snykers et al 2011), liver cells (Gu et al 2009;Lange et al 2005) and liver injury serum Lysy et al 2008) can induce BMMSCs to differentiate into hepatocytes in vitro and in vivo (Piryaei et al 2011;Stock et al 2010). Since growth factor protein is expensive and has a short halflife in vivo and large doses may result in hemodynamic abnormalities and serious side effects, genetherapy has become a targeted approach for delivery (Supp and Boyce 2002).…”

Section: Introductionmentioning

confidence: 99%

VEGF165 expressing bone marrow mesenchymal stem cells differentiate into hepatocytes under HGF and EGF induction in vitro

Yan

Xiao

et al. 2012

Cytotechnology

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A short half-life and low levels of growth factors in an injured microenvironment necessitates the sustainable delivery of growth factors and stem cells to augment the regeneration of injured tissues. Our aim was to investigate the ability of VEGF 165 expressing bone marrow mesenchymal stem cells (BMMSCs) to differentiate into hepatocytes when cultured with hepatocyte growth factor (HGF) and epidermal growth factor (EGF) in vitro. We isolated, cultured and identified rabbit BMMSCs, then electroporated the BMMSCs with VEGF 165 -pCMV6-AC-GFP plasmid. G418 was used to select transfected cells and the efficiency was up to 70%. The groups were then divided as follows: Group A was electroporated with pCMV6-AC-GFP plasmid ? HGF ? EGF and Group B was electroporated with VEGF 165 -pCMV6-AC-GFP plasmid ?HGF ? EGF. After 14 days, BMMSCs were induced into short spindle and polygonal cells. Alpha-fetoprotein (AFP) was positive and albumin (ALB) was negative in Group A, while both AFP and ALB were positive in group B on day 10. AFP and ALB in both groups were positive on day 20, but the quantity of AFP in group B decreased with prolonged time and was about 43.5% less than group A. The quantity of the ALB gene was increased with prolonged time in both groups. However, there was no significant difference between group A and B on day 10 and 20. Our results demonstrated that VEGF 165 -pCMV6-AC-GFP plasmid modified BMMSCs still had the ability to differentiate into hepatocytes. The VEGF 165 gene promoted BMMSCs to differentiate into hepatocyte-like cells under the induction of HGF and EGF, and reduced the differentiation time. These results have implications for cell therapies.

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Differentiation of Bone Marrow-derived Mesenchymal Stem Cells into Hepatocyte-like Cells on Nanofibers and Their Transplantation into a Carbon Tetrachloride-Induced Liver Fibrosis Model

Cited by 111 publications

References 45 publications

Behavior of mouse spermatogonial stem-like cells on an electrospun nanofibrillar matrix

Behavior of mouse spermatogonial stem-like cells on an electrospun nanofibrillar matrix

Hepatic differentiation from human mesenchymal stem cells on a novel nanofiber scaffold

VEGF165 expressing bone marrow mesenchymal stem cells differentiate into hepatocytes under HGF and EGF induction in vitro

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