Mesenchymal Progenitor Cells in spinal surgery – vertebral fusion or regeneration of the intervertebral disc? (#6)
Mesenchymal Progenitor cells (MPC) are a source of self-renewing, multipotent, undifferentiated cells that may be isolated from bone marrow, adipose tissue, muscle, synovium etc which possess the capacity to differentiate into cells of the mesenchymal lineage such as bone, cartilage, and tendon. The administration of autologous or allogeneic MPCs to sites of musculoskeletal injury offers the potential of repairing or regenerating new tissue within these sites provided that they are exposed to the right environmental stimuli. In addition, the administered MPCs can exert paracrine effects on the endogenous cells promoting their revitalisation and recruitment to the foci of injury. Irrespective of their origin, both endogenous and exogenous MPCs require a variety of cues to undergo phenotypic differentiation in situ. Cues include the interaction with components of the extracellular matrix, mechanical stimulation and exposure to a variety of cytokines, chemokines and growth factors (GFs). In the clinical arena, co-administration of MPCs with GFs to injured sites can present problems with respect to the short half-lives of these physiological proteins in the host and their potential to provoke adverse local reactions such as fibrosis or ectopic bone formation. Our previous research has demonstrated that the polysulfated polysaccharide, Pentosan Polysulfate (PPS) suppressed osteogenic but promoted chondrogenic differentiation of MPC in vitro. Using sheep models we have now shown that formulations of MPCs cryopreserved with PPS and seeded into collagen sponges not only improved the viability of the MPC, but also promoted the deposition of a cartilageous matrix inside interbody cages implanted between the vertebral bodies of the cervical spines. In the absence of PPS, the same number of MPC seeded onto collagen sponges placed in the same cages and at the same spinal levels promoted bone formation and near complete spinal fusion in some animals. As PPS has been registered as an anti-thrombotic/ant-lipidemic/anti-inflammatory agent in man for over 50 years, its formulation with MPCs offers the potential to provide an inexpensive and safe means of enhancing cartilage and disc repair in the clinic.