Bone regeneration: stem cell therapies and clinical studies in orthopaedics and traumatology

Abstract

Regenerative medicine seeks to repair or replace damaged tissues or organs, with the goal to fully restore structure and function without the formation of scar tissue. Cell based therapies are promising new therapeutic approaches in regenerative medicine. By using mesenchymal stem cells, good results have been reported for bone engineering in a number of clinical studies, most of them investigator initiated trials with limited scope with respect to controls and outcome. With the implementation of a new regulatory framework for advanced therapeutic medicinal products, the stage is set to improve both the characterization of the cells and combination products, and pave the way for improved controlled and well-designed clinical trials. The incorporation of more personalized medicine approaches, including the use of biomarkers to identify the proper patients and the responders to treatment, will be contributing to progress in the field. Both translational and clinical research will move the boundaries in the field of regenerative medicine, and a coordinated effort will provide the clinical breakthroughs, particularly in the many applications of bone engineering.

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…Under appropriate conditions MPCs could be differentiated into a variety of mesenchymal tissues such as bone, cartilage, tendon, ligament, marrow stroma, muscle, fat and dermis [4,[49][50][51][52][53]. To induce fracture healing, MPCs are expanded ex vivo prior to their autologous grafting to the fracture site and differentiated into osteogenic lineages to promote bone regeneration [9,54]. Such cell-based strategy approaches have been used to demonstrate that autologous bone marrow-derived MPC transplantation was superior compared to unloaded scaffold [5,7].…”

Advances in stem cell therapy for spinal cord injury

“…In contrast, there are 50 years of research in the adult stem cell field with HSCs, which are routinely used to treat patients with leukemia and related bone/blood cancers. Many clinical case reports describing MSC therapy for stroke, multiple sclerosis, and in orthopedic conditions have been published (125)(126)(127)(128). Given the large amount of preclinical data and the safety record, it is understandable that so many clinical trials have used MSC-based therapies.…”

On the Genealogy of Tissue Engineering and Regenerative Medicine

“…Regeneration of dentine-pulp complex using cells encapsulated within scaffolds; treatment of periodontal defects through guided bone regeneration membrane, growth factors and cytokines; and replacement of lost teeth by transplantation of the bioengineered tooth germ constitute state of the art of the rudimentary practice of employing blue nacre shells as functional dental substitutes (by the Mayans circa 600 AD). These advancements have been reviewed by Abou Neel et al 88 Transplantation of bone marrow stem cells (encapsulated within a suitable scaffold), 89 to repair articular cartilage (patellar, patellofemoral, and femoral) 90 and osteochondral defects 90 as well as local bone defects 91 in humans forms another significant achievement of a TERM therapy 89 practiced first by the Egyptians. The use of TERM to treat skeletal defects has been reviewed elsewhere.…”

“…The use of TERM to treat skeletal defects has been reviewed elsewhere. 89,91,92 While TERM is still decades away from replicating the feat mentioned in the Mahabharata and Faust, of creating human forms within a phial, the existing technology has made possible development and availability of tissues and, very recently, organs for clinical applications. A bioengineered vessel implanted to replace the right intermediate pulmonary artery in a child suffering from single right ventricle and pulmonary atresia epitomizes the state of the art.…”