Recent Advances in Mechanically Loaded Human Mesenchymal Stem Cells for Bone Tissue Engineering

Large bone defects are a major health concern worldwide. The conventional bone repair techniques (e.g., bone-grafting and Masquelet techniques) have numerous drawbacks, which negatively impact their therapeutic outcomes. Therefore, there is a demand to develop an alternative bone repair approach that can address the existing drawbacks. Bone tissue engineering involving the utilization of human mesenchymal stem cells (hMSCs) has recently emerged as a key strategy for the regeneration of damaged bone tissues. However, the use of tissue-engineered bone graft for the clinical treatment of bone defects remains challenging. While the role of mechanical loading in creating a bone graft has been well explored, the effects of mechanical loading factors (e.g., loading types and regime) on clinical outcomes are poorly understood. This review summarizes the effects of mechanical loading on hMSCs for bone tissue engineering applications. First, we discuss the key assays for assessing the quality of tissue-engineered bone grafts, including specific staining, as well as gene and protein expression of osteogenic markers. Recent studies of the impact of mechanical loading on hMSCs, including compression, perfusion, vibration and stretching, along with the potential mechanotransduction signalling pathways, are subsequently reviewed. Lastly, we discuss the challenges and prospects of bone tissue engineering applications

Effects of cryopreservation conditions on human adipose-derived mesenchymal stem cells and its potential application in cardiac fibrosis / Yong Kar Wey

Human adipose-derived mesenchymal stem cells (hASCs) hold great potential for clinical application (e.g., regenerative medicine and cell-based therapies) due to their multilineage differentiation ability and paracrine function. To achieve sufficient numbers of hASCs for off-the-shelf-use in an intensive clinical setting (e.g., cardiac fibrosis therapy), hASCs at early passage should be capable of being cryopreserved in the long-term with cell functionality maintained without raising biosafety concerns (e.g., tumourigenesis). The objectives of this study are to evaluate the effects of cryopreservation conditions on hASCs and the potential application of cryopreserved hASCs in cardiac fibrosis. In this study, hASCs were cryopreserved for 3 months using a slow freezing method in various combinations of 3 general used cryoprotective agents (CPAs), including dimethylsulfoxide (DMSO), trehalose, and fetal bovine serum (FBS). Following rapid thawing, hASCs cryopreserved in a cryopreservation medium containing DMSO at a reduced concentration without FBS (5% DMSO) were found to maintain high viability and functional properties in terms of differentiation potential (including adipogenic, osteogenic and chondrogenic), proliferation potential, and stemness. Moreover, hASCs cryopreserved in 5% DMSO have a low risk of tumourigenesis, as indicated by normal expression levels of tumour suppressor markers and human telomerase reverse transcriptase (hTERT), normal telomere length, and normal telomerase activity without significant DNA damage or p53 mutation. In addition, it was found that fresh (non-cryopreserved) hASCs and hASCs cryopreserved in 5% DMSO both display a similar potential to inhibit cardiac myofibroblast differentiation in vitro via paracrine signalling, and thus may decrease the incidence of cardiac fibrosis. In summary, 5% DMSO without FBS may be an ideal CPA for efficient long-term cryopreservation of iv hASCs for clinical applications. Further, long-term cryopreserved hASCs demonstrate their significant therapeutic value in cardiac fibrosis therapy

Editorial for the Special Issue on Point-of-Care Devices

Point-of-care (POC) devices, such as paper- and chip-based devices enable the quick collection of patients’ health information to improve healthcare [...

Emerging Point-of-care Technologies for Food Safety Analysis

Food safety issues have recently attracted public concern. The deleterious effects of compromised food safety on health have rendered food safety analysis an approach of paramount importance. While conventional techniques such as high-performance liquid chromatography and mass spectrometry have traditionally been utilized for the detection of food contaminants, they are relatively expensive, time-consuming and labor intensive, impeding their use for point-of-care (POC) applications. In addition, accessibility of these tests is limited in developing countries where food-related illnesses are prevalent. There is, therefore, an urgent need to develop simple and robust diagnostic POC devices. POC devices, including paper- and chip-based devices, are typically rapid, cost-effective and user-friendly, offering a tremendous potential for rapid food safety analysis at POC settings. Herein, we discuss the most recent advances in the development of emerging POC devices for food safety analysis. We first provide an overview of common food safety issues and the existing techniques for detecting food contaminants such as foodborne pathogens, chemicals, allergens, and toxins. The importance of rapid food safety analysis along with the beneficial use of miniaturized POC devices are subsequently reviewed. Finally, the existing challenges and future perspectives of developing the miniaturized POC devices for food safety monitoring are briefly discussed.Applied Science, Faculty ofOther UBCNon UBCMechanical Engineering, Department ofReviewedFacult

Recent Advances in Mechanically Loaded Human Mesenchymal Stem Cells for Bone Tissue Engineering

Large bone defects are a major health concern worldwide. The conventional bone repair techniques (e.g., bone-grafting and Masquelet techniques) have numerous drawbacks, which negatively impact their therapeutic outcomes. Therefore, there is a demand to develop an alternative bone repair approach that can address the existing drawbacks. Bone tissue engineering involving the utilization of human mesenchymal stem cells (hMSCs) has recently emerged as a key strategy for the regeneration of damaged bone tissues. However, the use of tissue-engineered bone graft for the clinical treatment of bone defects remains challenging. While the role of mechanical loading in creating a bone graft has been well explored, the effects of mechanical loading factors (e.g., loading types and regime) on clinical outcomes are poorly understood. This review summarizes the effects of mechanical loading on hMSCs for bone tissue engineering applications. First, we discuss the key assays for assessing the quality of tissue-engineered bone grafts, including specific staining, as well as gene and protein expression of osteogenic markers. Recent studies of the impact of mechanical loading on hMSCs, including compression, perfusion, vibration and stretching, along with the potential mechanotransduction signalling pathways, are subsequently reviewed. Lastly, we discuss the challenges and prospects of bone tissue engineering applications.Applied Science, Faculty ofMedicine, Faculty ofNon UBCMechanical Engineering, Department ofReviewedFacult

Mesenchymal Stem Cell Therapy for Ischemic Tissues

Ischemic diseases such as myocardial infarction, ischemic stroke, and critical limb ischemia are immense public health challenges. Current pharmacotherapy and surgical approaches are insufficient to completely heal ischemic diseases and are associated with a considerable risk of adverse effects. Alternatively, human mesenchymal stem cells (hMSCs) have been shown to exhibit immunomodulation, angiogenesis, and paracrine secretion of bioactive factors that can attenuate inflammation and promote tissue regeneration, making them a promising cell source for ischemic disease therapy. This review summarizes the pathogenesis of ischemic diseases, discusses the potential therapeutic effects and mechanisms of hMSCs for these diseases, and provides an overview of challenges of using hMSCs clinically for treating ischemic diseases

In Vitro Human Cancer Models for Biomedical Applications

Cancer is one of the leading causes of death worldwide, and its incidence is steadily increasing. Although years of research have been conducted on cancer treatment, clinical treatment options for cancers are still limited. Animal cancer models have been widely used for studies of cancer therapeutics, but these models have been associated with many concerns, including inaccuracy in the representation of human cancers, high cost and ethical issues. Therefore, in vitro human cancer models are being developed quickly to fulfill the increasing demand for more relevant models in order to get a better knowledge of human cancers and to find novel treatments. This review summarizes the development of in vitro human cancer models for biomedical applications. We first review the latest development in the field by detailing various types of in vitro human cancer models, including transwell-based models, tumor spheroids, microfluidic tumor-microvascular systems and scaffold-based models. The advantages and limitations of each model, as well as their biomedical applications, are summarized, including therapeutic development, assessment of tumor cell migration, metastasis and invasion and discovery of key cancer markers. Finally, the existing challenges and future perspectives are briefly discussed.Other UBCNon UBCReviewedFacultyResearche

Hypoxia enhances the viability, growth and chondrogenic potential of cryopreserved human adipose-derived stem cells

Cryopreservation is the only existing method of storage of human adipose-derived stem cells (ASCs) for clinical use. However, cryopreservation has been shown to be detrimental to ASCs, particularly in term of cell viability. To restore the viability of cryopreserved ASCs, it is proposed to culture the cells in a hypoxic condition. To this end, we aim to investigate the effect of hypoxia on the cryopreserved human ASCs in terms of not only cell viability, but also their growth and stemness properties, which have not been explored yet. In this study, human ASCs were cultured under four different conditions: fresh (non-cryopreserved) cells cultured in 1) normoxia (21% O2) and 2) hypoxia (2% O2) and cryopreserved cells cultured in 3) normoxia and 4) hypoxia. ASCs at passage 3 were subjected to assessment of viability, proliferation, differentiation, and expression of stemness markers and hypoxia-inducible factor-1 alpha (HIF-1α). We found that hypoxia enhances the viability and the proliferation rate of cryopreserved ASCs. Further, hypoxia upregulates HIF-1α in cryopreserved ASCs, which in turn activates chondrogenic genes to promote chondrogenic differentiation. In conclusion, hypoxic-preconditioned cryopreserved ASCs could be an ideal cell source for cartilage repair and regeneration