Mesenchymal stem cells: mechanisms and role in bone regeneration

Abstract

Stimulating bone growth and regeneration, especially in patients with delayed union or non-union of bone, is a challenge for orthopaedic surgeons. Treatments employed for bone regeneration are based on the use of cells, biomaterials and factors. Among these therapies, cell treatment with mesenchymal stem cells (MSCs) has a number of advantages as MSCs: (1) are multipotent cells that can migrate to sites of injury; (2) are capable of suppressing the local immune response; and (3) are available in large quantities from the patients themselves. MSC therapies have been used for stimulating bone regeneration in animal models and in patients. Methods of application range from direct MSC injection, seeding MSCs on synthetic scaffolds, the use of gene-modified MSCs, and hetero-MSCs application. However, only a small number of these cell-based strategies are in clinical use, and none of these treatments has become the gold standard treatment for delayed or non-union of bone.

Study of the involvement of allogeneic MSCs in bone formation using the model of transgenic mice

“…Many studies report specifically on the application of MSCs to treat critical-size bone defects. 6,7,[24][25][26] Grafts based on 3D-scaffolds carrying MSCs for curing bone defects have demonstrated excellent results. Good integration of an implant, 27 vascularization of the grafted zone, 28 extracellular matrix formation and grafts' mineralization 29 have been demonstrated using different types of scaffolds and seeded MSCs.…”

“…18,19 The involvement of seeded cells in the stimulation and promotion of bone regeneration in vivo remains one of great uncertainties in the MSCs studies. 6 It is not completely understood what happens to MSCs seeded onto scaffolds when they are implanted into a bone defect, and whether they are involved directly in the bone formation. The purpose of the present study was to establish the involvement of seeded allogeneic MSCs in the bone formation in vivo, using a model of transgenic mice and genetically labeled cells.…”

“…5 Under certain in vitro conditions MSCs are capable of differentiating into osteoblasts, adipose cells, cartilage cells, skeletal muscle cells and even into neuron-like cells. 6,12 MSCs lack expression of the major histocompatibility complex I and of costimulatory molecules like CD40, CD80, and CD86, which makes them largely nonimmunogenic. 13 Furthermore, these cells are capable of suppressing the immune system via still unknown mechanisms, thus, the treatment with such allogeneic cells is largely immunoinert.…”

“…Several cell types can potentially be used as a cellular material, but mesenchymal stem cells (MSCs) have been considered the most attractive type for such a bone replacement. [5][6][7] Mesenchymal stem cells, also known as multipotent mesenchymal stromal cells, are self-renewing cells which can be easily isolated from a small aspirate of bone marrow or adipose tissue and then expanded to clinical scales in vitro. 7 However, the bone marrow and adipose tissue are not the only sources of MSCs.…”

Mini-invasive treatment for delayed or nonunion: the use of percutaneous autologous bone marrow injection

“…Beside mechanical and biochemical aspects, biological processes played a major role in the causes of delayed or nonunion fracture in recent studies (Bhargava, 2007;Bigham-Sadegh, 2014;Hernigou, 2005b). The rate of bone union was influenced by the cellular proliferation that results in the formation of the callus, the periosteum, and the status of bone marrowin the generation of osteoblasts (Fox, 2014;Hernigou, 2005b;Qin, 2014). Studies of Hernigou et al showed that deficiency in the population of local connective tissue by progenitors may happen in the cases of previous infection,…”