The Combined Use of Mesenchymal Stromal Cells and Scaffolds for Bone Repair

Abstract

A general principle of stem cell therapy is to exploit the natural ability of the human body to heal through the process of regeneration. Here, we review the current status of cell therapy based on adult mesenchymal stem cells (MSC) with emphasis on therapeutic application in bone-related diseases. The main issues for an effective bone engineering strategy include: - A sufficient number of bone-forming cells, where cell yield, separation, expansion, commitment, as well as patient age, are all variables to be considered; - An ECM-like scaffold conductive for and informative to cells, where structural/physico-chemical/mechanical parameters, administration form (injectable or free-form), and degradation rate have to be tuned according to the clinical application; - Biochemical signals, such as growth factors/cytokines to induce osteogenic differentiation, where the choice between autogenous or exogenous sourcing, dose, timing, etc. are critical; - An adequate blood supply, provided by angiogenetic factors, pre-vascularization, pre-implant co-culture of vessel and bone progenitors. We also discuss the safety and efficacy of different approaches, as well as bottlenecks hampering rapid translation of adult MSC therapy from the laboratories to the clinics. A central paradigm for the effective regeneration of bone tissue is the re-creation at the site of injury of a microenvironment as close as possible to the natural MSC repository in the body. This would allow adult MSC to serve as cellular factories, i.e. to express paracrine activity in situ by secretion of inflammatory and reparative cytokines and to cooperate with other cells. The results from a wide array of in vitro and in vivo studies, as well as from some clinical trials, are expanding the range of clinical protocols for bone repair, that is the ultimate goal of orthopaedics.

Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine

“…Recent studies have also brought attention to the wide array of bioactive factors produced by MSCs, which may play an important role in the regulation of numerous physiological processes [ 44 ]. Therefore, the secretome from MSCs has attracted much attention for its potential use in tissue repair and regeneration [ 43 , 45 , 46 , 47 ].…”

Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy

“…For bone tissue engineering applications, these cells are used in combination with “scaffolds” that are designed to allow cell adhesion, survival and growth and that are even functionalized to provide cells with pro-osteogenic stimuli (Warnke et al, 2004; Marcacci et al, 2007). The advantage of using mesenchymal osteogenic precursors relies not only on the ability of these cells to differentiate into osteoblasts, but also on their capacity to provide trophic signals as growth factors and cytokines to the damaged tissues, thereby accelerating the regeneration process (Ciapetti et al, 2012). …”

Cell density, dimethylsulfoxide concentration and needle gauge affect hydrogel-induced bone marrow mesenchymal stromal cell viability

“…They can also protect encapsulated cells from inflammation and surrounding macrophages [6], and improve the acute cell viability of stem cells [22]. In preclinical and clinical studies, MSC transplantation with biomaterials have shown greater benefits than without biomaterials in skeletal and bone tissue regeneration [23]. HyStem-C is a hyaluronic acid (HA)-based injectable biomaterial, which has been shown to approximate the biomechanical properties of the tissue and encourage ECM regeneration [7, 24–26].…”