Schwann Cells and the Regrowth of Axons in the Mammalian Cns: A Review of Transplantation Studies in the Rat Visual System

Abstract

1. We have used peripheral nerve transplants or cultured Schwann cells grafted in association with different types of polymer to study axonal regrowth in the rat visual system. In some instances the glia were co-grafted with fetal tectal tissue. 2. The studies have two main aims: (i) to determine whether retinal axons can be induced to regrow at a site distant from their cell soma, that is, after damage to the brachial region of the optic tract; (ii) to determine whether retinal axons exposed to Schwann cells retain the ability to recognize their appropriate target neurons in CNS tissue. 3. In brachial lesion studies, Schwann cells were placed in the lesion site in association with nitrocellulose papers, within polycarbonate tubes in the presence or absence of a supporting extracellular matrix (ECM), or within polymer hydrogel scaffolds. Autologous sciatic nerve grafts were also used. Immunohistochemical studies revealed the presence of regenerating axons within all polymer bridges. Regrowth of retinal axons was also seen, however, growth was not extensive and was limited to the proximal 1-1.5 mm of the implants. 4. In target innervation experiments, two surgical paradigms were developed. In one experiment, a segment of sciatic nerve was autografted onto the transected optic nerve in adult rats and the distal end of each graft was placed adjacent to fetal tectal (target) tissue implanted into the frontal cortex. To date, we have not been able to demonstrate selective recognition of target regions within tectal transplants by retinal axons exiting the sciatic nerve implants. 5. In the second experiment, Schwann cells were mixed with fetal tectal cells and co-grafted to the midbrain of newborn host rats. Schwann cells altered the characteristic pattern of host retinal growth into tectal grafts; in some cases axons were induced to grow away from appropriate target areas by nearby co-grafted Schwann cells. 6. In summary, Schwann cell/polymer scaffolds may provide a useful way of promoting the regrowth of damaged axons in the CNS, however: (i) in adults, at least, their effectiveness is reduced if they are located at a distance from the cell bodies giving rise to regenerating axons; (ii) in some circumstances exposure to a peripheral glial environment may affect the capacity of regenerating axons to recognize appropriate target cells in the CNS neuropil.

The CNS lesion scar: new vistas on an old regeneration barrier

“…In the past a substantial number of different experimental approaches have been made to drive regrowing axons, e.g., by the use of neurotrophins (Bregman et al 1997;Houle et al 1996;Tuszynski et al 1996), the transplantation of nerve grafts (Vidal-Sanz et al 1987;Cheng et al 1996), Schwann cells (Harvey et al 1995;Paino et al 1994;Stichel et al 1996;Xu et al 1995), olfactory ensheathing cells (Ramon-CuØto et al 1998;Ramon-CuØto and Nieto-Sampedro 1994;Li et al 1997) and microglia/macrophages (Franzen et al 1998;Rabchevsky and Streit 1997;Lazarov-Spiegler et al 1996) or the neutralization of myelin-associated growth inhibitors (Schnell et al 1994;Schnell and Schwab 1990). Most of these approaches succeeded in stimulating axon growth but failed to elongate the lesioned axons within their appropriate pathway.…”

“…Unfortunately, the unavoidable, additional attack of the BM of blood vessels led to severe changes in vascular supply and limited the regeneration success. Another more indirect way to modify the nature of the BM is the implantation of glial cells, such as astrocytes or Schwann cells (Emmett et al 1988;Smith and Miller 1991;Wunderlich et al 1994;Stichel et al 1996;Raisman et al 1993;Harvey et al 1995;Martin et al 1991;Brook et al 1994) (Table 2). In our own work we have used the minimal invasive microtransplantation approach to introduce a Schwann cell suspension into the transected postcommissural fornix (Stichel et al 1996).…”

Mesenchymal Stem Cells and Umbilical Cord as Sources for Schwann Cell Differentiation: their Potential in Peripheral Nerve Repair

“…These cells overcome the inhibitory environment to elicit axonal regeneration and construct myelin in the CNS [12,13]. For these reasons, Schwann cells are considered one of the most suitable cell types for inducing axonal regeneration in both the PNS and CNS.…”

Novel method to obtain highly enriched cultures of adult rat Schwann cells

“…SCs have been extensively investigated for cell therapy in a variety of CNS injury models, including the spinal cord (Pearse et al 2004; Barakat et al 2005), brain (Kromer and Cornbrooks 1985), and optic nerve (Harvey et al 1995). Moreover, autologous nerve grafting or biodegradable conduits are the gold standard for peripheral nerve repair (Mackinnon and Dellon 1990).…”