Adult Bone Marrow Stem Cells and Biocompatible Polymers in SCI Repair, pp. 297-320
Authors: A. Hejčl, P. JendelovŠ and E. SykovŠ
Abstract: Spinal cord injury (SCI) is a complex and dynamic process that will require multiple approaches to yield successful therapy. Bone marrow stem cells and biomaterials represent an important part of SCI neurotransplantation research in the last decade. The behavior of rat and human mesenchymal stem cells (MSCs) grafted to the injured spinal cord has been studied in terms of the cellsí participation in lesion repair, their differentiation and their ability to promote functional recovery. The fate of MSCs has been followed using cells labeled in culture with superparamagnetic iron-oxide nanoparticles. The effects of implanted rat MSCs was compared with the implantation of a freshly prepared mononuclear fraction of bone marrow cells (BMCs) or the injection of granulocyte colony-stimulating factor. Lesioned animals grafted with MSCs, BMCs or treated with G-CSF had significantly smaller lesions and better motor performance. The transplantation of MSCs in animal models of chronic SCI (which result in cavity formation) led to only modest improvement. Autologous BMC implantation was used in a Phase I/II clinical trial in patients with SCI. Intra-arterial vs. intravenous administration and groups of acute vs. chronic patients were compared. Implantation was safe; in addition, 5 out of 6 patients with a subacute cervical lesion improved their function following the administration of BMCs via a. vertebralis. Various biomaterials, such as hydrogels and nanofibers, have been used to bridge large pseudocystic cavities. Scaffolds may bridge the gap left after a population of cells is lost and may also serve as carriers for stem cells, thus supporting tissue reconstruction. Hydrogels and nanofibers based on copolymers of 2-hydroxypropylmethacrylamide and 2-hydroxyethylmethacrylate were implanted in animals with SCI to provide a bridge across the pseudocystic cavity and to serve as a scaffold for tissue regeneration. Various physical and chemical modifications of these scaffolds, which were evaluated in vivo, are discussed. Both therapeutic modalities, i.e. MSCs and hydrogels, can be applied together to combine the advantages of both therapeutic approaches. Hydrogels were used as 3D carriers for stem cells and implanted into acute spinal cord lesions. Various hydrogels are suitable as carriers of MSCs and/or other stem cells, as the cells survived in the hydrogels for several months. Further, these hydrogel constructs (hydrogel+MSCs) were also tested in an animal model of chronic SCI. The hydrogel constructs seeded with MSCs created a successful bridge, preventing tissue atrophy and improving functional outcome.