Biomaterials and Gene Therapy: A Smart Combination for MSC Musculoskeletal Engineering.

Musculoskeletal pathologies, especially those affecting bones and joints, remain a challenge for regenerative medicine. The main difficulties affecting bone tissue engineering are the size of the defects, the need for blood vessels and the synthesis of appropriate matrix elements in the engineered tissue. Indeed, the cartilage is an avascular tissue and consequently has limited regenerative abilities. Thanks to their self-renewal, plasticity and immunomodulatory properties, mesenchymal stem cells (MSCs) became a central player in tissue engineering, and have already been shown to be able to differentiate towards chondrogenic or osteogenic phenotypes. Whether synthetic (e.g. tricalcium phosphate) or from natural sources (e.g. hyaluronic acid), biomaterials can be shaped to fit into bone and cartilage defects to ensure mechanical resistance and may also be designed to control cell spatial distribution or differentiation. Soluble factors are classically used to promote cell differentiation and to stimulate extracellular matrix synthesis to achieve the desired tissue production. But as they have a limited lifetime, transfection using plasmid DNA or transduction via a viral vector of therapeutic genes to induce the cell secretion of these factors allows to have more lasting effects. Also, the chondrocyte phenotype may be difficult to control over time, with for example the production of hypertrophic or osteogenic markers that is undesirable in hyaline cartilage. Thus, tissue regeneration strategies became more elaborate, with an attempt at associating the benefits of MSCs, biomaterials, and gene therapy to achieve a proper tissue repair. This minireview focuses on in vitro and in vivo studies combining biomaterials and gene therapy associated with MSCs for bone and cartilage engineering.

How Do Mesenchymal Stem Cells Influence or Are Influenced by Microenvironment through Extracellular Vesicles Communication?

Mesenchymal stem cells (MSCs) are widely used in cell therapy and tissue engineering thanks to their self-renewal, their multipotency, and their immunomodulatory properties that make them an attractive tool for regenerative medicine. A large part of MSCs positive effects is due to their secretion products which participate in creating a favorable microenvironment and closely relate these cells to other cell types. Extracellular vesicles (EVs) belong to cellular secretions. They are produced by cells continuously or after stimulation (e.g., calcium flux, cellular stress) and act in tissue homeostasis and intercellular communication. The understanding of the role of EVs is growing, more particularly their impact on cell migration, differentiation, or immunomodulation. EVs derived from MSCs show these interesting properties that may be considered in therapeutics, although they can have adverse effects by facilitating cancer propagation. Moreover, MSC behavior may also be influenced (proliferation, differentiation) by EVs derived from other donor cells. The aim of this mini review is to summarize the two-way communication between MSCs and other cell types, and how they can affect each other with their microenvironment through EVs. On the one hand, the manuscript presents the influence of MSC-derived EVs on diverse recipient cells and on the other hand, the effects of EVs derived from various donor cells on MSCs. The discrepancies between cancer cells and MSCs communication according to the sources of MSCs but also the tumor origins are also mentioned.

Human umbilical cord derived matrix: A scaffold suitable for tissue engineering application.

BACKGROUND: Human tissue derived natural extracellular matrix (ECM) has great potential in tissue engineering. OBJECTIVE: We sought to isolate extracellular matrix derived from human umbilical cord and test its potential in tissue engineering. METHODS: An enzymatic method was applied to isolate and solubilized complete human umbilical cord derived matrix (hUCM). The obtained solution was analyzed for growth factors, collagen and residual DNA contents, then used to coat 2D and 3D surfaces for cell culture application. RESULTS: The hUCM was successfully isolated with trypsin digestion to acquire a solution containing various growth factors and collagen but no residual DNA. This hUCM solution can form a coating on 2D and 3D substrates suitable cell culture. CONCLUSION: We developed a new matrix derived from human source that can be further used in tissue engineering.