The use of large animals to facilitate the process of MSC going from laboratory to patient—‘bench to bedside’

Hotham, William Edward; Henson, Fmd

doi:10.1007/s10565-020-09521-9

Cited by 16 publications

(22 citation statements)

References 104 publications

(67 reference statements)

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“…Before clinical application, cellular and molecular interactions are studied in vitro. Afterwards, small animal models facilitate the initial “proof of concept,” whereas large animal models allow for the examination of the safety, dosing, and efficacy of MSCs prior to clinical application [ 26 ]. Although human MSCs have been extensively investigated, sheep MSCs are still poorly characterized [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Biological Characteristics and Osteogenic Differentiation of Ovine Bone Marrow Derived Mesenchymal Stem Cells Stimulated with FGF-2 and BMP-2

Gromolak

Krawczenko

Antończyk

et al. 2020

IJMS

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Cell-based therapies using mesenchymal stem cells (MSCs) are a promising tool in bone tissue engineering. Bone regeneration with MSCs involves a series of molecular processes leading to the activation of the osteoinductive cascade supported by bioactive factors, including fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2). In this study, we examined the biological characteristics and osteogenic differentiation potential of sheep bone marrow MSCs (BM-MSCs) treated with 20 ng/mL of FGF-2 and 100 ng/mL BMP-2 in vitro. The biological properties of osteogenic-induced BM-MSCs were investigated by assessing their morphology, proliferation, phenotype, and cytokine secretory profile. The osteogenic differentiation was characterized by Alizarin Red S staining, immunofluorescent staining of osteocalcin and collagen type I, and expression levels of genetic markers of osteogenesis. The results demonstrated that BM-MSCs treated with FGF-2 and BMP-2 maintained their primary MSC properties and improved their osteogenic differentiation capacity, as confirmed by increased expression of osteocalcin and collagen type I and upregulation of osteogenic-related gene markers BMP-2, Runx2, osterix, collagen type I, osteocalcin, and osteopontin. Furthermore, sheep BM-MSCs produced a variety of bioactive factors involved in osteogenesis, and supplementation of the culture medium with FGF-2 and BMP-2 affected the secretome profile of the cells. The results suggest that sheep osteogenic-induced BM-MSCs may be used as a cellular therapy to study bone repair in the preclinical large animal model.

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Section: Discussionmentioning

confidence: 99%

Biological Characteristics and Osteogenic Differentiation of Ovine Bone Marrow Derived Mesenchymal Stem Cells Stimulated with FGF-2 and BMP-2

Gromolak

Krawczenko

Antończyk

et al. 2020

IJMS

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“…The mice were provided with ad libitum access to food and water and were allowed to acclimatise to the new environment for 1 week prior to experimentation. All experimental studies followed the Guide for the Care and Use of Laboratory Animals ( 25 ). The present study was approved by the Ethics Commission for Animal Tests of the Nanjing University of Traditional Chinese Medicine (Nanjing, China).…”

Section: Methodsmentioning

confidence: 99%

Maiwei Yangfei decoction prevents bleomycin‑induced pulmonary fibrosis in mice

Peng

Han

et al. 2021

Exp Ther Med

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Maiwei Yangfei (MWYF) is a compound Chinese herb that is safe and effective in the clinical setting in patients with pulmonary fibrosis (PF). The aim of the present study was to assess the role of a (MWYF) decoction in a bleomycin (BLM)-induced PF mouse model and to investigate the underlying functional mechanism. Chemical components within the MWYF decoction were analysed using liquid chromatography-mass spectrometry. A total of 50 C57BL/6 mice were randomly assigned to one of the following five groups with 10 mice per group: Control, model, low dose MWYF (20 g/kg), medium dose MWYF (40 g/kg) and high dose MWYF (60 g/kg). A mouse PF model was established by the tracheal instillation of BLM (5 mg/kg) prior to MWYF treatment, except for mice in the control group. After 21 days of treatment with MWYF, the mice were sacrificed and the body weights were recorded. In addition, pulmonary tissues and bronchial alveolar lavage fluid were collected. TNF-α, IL-6, IL-17, hydroxyproline, pyridinoline and collagen I levels were determined using ELISA. Vimentin, α-smooth muscle actin (α-SMA), fibronectin, TGF-β1, Smad3, TNF-α, IL-6, IL-17, collagen I and collagen III were determined using western blotting. Vimentin and α-SMA levels were also determined using immunofluorescence analysis. Collagens I and III were detected using immunohistochemical analysis and TGF-β1 and Smad3 levels were determined using reverse transcription-quantitative PCR. Following treatment with MWYF decoction, the body weight of the mice in the PF group increased, the degree of pulmonary alveolitis and PF was reduced, collagen levels were reduced and the expression levels of α-SMA, vimentin and fibronectin were decreased. Although both protein and mRNA expression levels of TGF-β1 and Smad3 were reduced, they remained higher than those observed in the control group. To conclude, MWYF decoction delayed the development of BLM-induced PF in mice, where the functional mechanism was likely associated with the TGF-β1/Smad3 signalling pathway.

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“…The obvious advantages of these models are well known, being easy handling, low costs, and high reproductive rates [12]. Rodents, rabbits, and guinea pigs are considered the main small animal species [13].…”

Section: Small Animal Modelsmentioning

confidence: 99%

“…Large animal models include sheep, goats, cows, pigs, horses, dogs, and primates. Among these, the most commonly used species are canines, swine, and nonhuman primates (NHPs) [9,13]. They all have similarities to human physiology and anatomy, which makes them suitable for preclinical studies.…”

Section: Large Animal Modelsmentioning

confidence: 99%

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Animal Models in Allogenic Solid Organ Transplantation

Wenzel¹,

Blasczyk²,

Figueiredo³

2021

Transplantology

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Animal models provide the link between in vitro research and the first in-man application during clinical trials. They provide substantial information in preclinical studies for the assessment of new therapeutic interventions in advance of human clinical trials. However, each model has its advantages and limitations in the ability to imitate specific pathomechanisms. Therefore, the selection of an animal model for the evaluation of a specific research question or evaluation of a novel therapeutic strategy requires a precise analysis. Transplantation research is a discipline that largely benefits from the use of animal models with mouse and pig models being the most frequently used models in organ transplantation research. A suitable animal model should reflect best the situation in humans, and the researcher should be aware of the similarities as well as the limitations of the chosen model. Small animal models with rats and mice are contributing to the majority of animal experiments with the obvious advantages of these models being easy handling, low costs, and high reproductive rates. However, unfortunately, they often do not translate to clinical use. Large animal models, especially in transplantation medicine, are an important element for establishing preclinical models that do often translate to the clinic. Nevertheless, they can be costly, present increased regulatory requirements, and often are of high ethical concern. Therefore, it is crucial to select the right animal model from which extrapolations and valid conclusions can be obtained and translated into the human situation. This review provides an overview in the models frequently used in organ transplantation research.

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The use of large animals to facilitate the process of MSC going from laboratory to patient—‘bench to bedside’

Cited by 16 publications

References 104 publications

Biological Characteristics and Osteogenic Differentiation of Ovine Bone Marrow Derived Mesenchymal Stem Cells Stimulated with FGF-2 and BMP-2

Biological Characteristics and Osteogenic Differentiation of Ovine Bone Marrow Derived Mesenchymal Stem Cells Stimulated with FGF-2 and BMP-2

Maiwei Yangfei decoction prevents bleomycin‑induced pulmonary fibrosis in mice

Animal Models in Allogenic Solid Organ Transplantation

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