Do foetal neural grafts induce repair by the injured juvenile neocortex?

Multifaceted dialogue between graft and host in neurotransplantation

“…An alternative mechanism responsible for the observed recovery of the mesencephalic DA cells, namely, de novo neurogenesis involving proliferation of host cells, was excluded in BrdU‐labeling experiments on transplanted animals. In accordance with the earlier formulated hypothesis (Ourednik et al, 1993, 1998), a damaged host CNS can benefit from transplanted NSCs not only because of their replacement of damaged tissue but also because of a dialogue between graft and host cells leading to significant sparing and neuroprotection (rescue) of damaged but persisting host cytoarchitecture. Moreover, the study above indicated that such phenomena can occur not only in dysfunctional immature and young adult CNS, but also in the aging brain, where slow and protracted nonapoptotic neurodegenerative processes generally do occur (Jellinger and Stadelmann, 2000).…”

“…In the early 1990s, it was found that grafted fetal neural tissue may actually induce host plasticity leading to repair in a manner not seen to occur spontaneously (Ourednik et al, 1993). In a series of grafting experiments, primary neural tissue from fetal mouse neopallium was transplanted into the mechanically damaged barrelfield area of primary somatosensory cortex of juvenile mice (uniform size and severity of the prepared cavity was assured by using a calibrated wire knife; see also Andres and Van der Loos, 1985).…”

“…Based on the observation of graft‐induced host plasticity in damaged mouse and kitten neocortex, we suggested that this “regenerative phenomenon” is likely to depend on a favorable cellular and molecular environment that had to be created in a specific and reciprocal communication between graft and host elements, because neither non‐grafted cavities nor cavities receiving non‐neural fetal tissue presented any signs of recovery (Ourednik et al, 1993, 1998). Certain cellular elements within the fairly heterogeneous fetal tissue grafts seemed to modify the brain environment such that intrinsic, albeit latent, regenerative responses by the host were being triggered, uncovered, or amplified.…”

Graft/Host Relationships in the Developing and Regenerating CNS of Mammals

“…Today, it seems more and more obvious (and we were among the first proponents of this idea back in the early “90s23) that the ability to replace damaged or missing cell populations or to deliver missing enzymes and structural molecules is by far not the only beneficial feature of grafted fetal tissue and NSCs that deserves all the credit. In the light of new findings regarding postnatal CNS plasticity24 and intercellular graft/host communication,25 a much broader image begins to emerge of the roles and consequences of this complex cellular/molecular dialogue between essentially two different worlds coming together.…”

“…In the early “90s, together with the late Hendrik Van der Loos, we worked on repairing a mechanically damaged somatosensory cortex by transplanting fetal tissue into juvenile mice. After a series of grafting experiments, we observed that, instead of replacing the damaged and missing cells in the unilaterally created cortical cavity in the primary somatosensory barrel field area, primary neural tissue isolated from embryonic day 14 (ED14) mouse neopallium could induce repair from within the juvenile host in a manner not seen spontaneously in the absence of transplantation 23. The reconstituted cavity (in 70–80% of cases) appeared to become “filled” by relatively well‐organized cortical tissue of host origin that even presented cellular arrangements reminiscent of barrels, which even displayed, at least partially, electrical activity (unpublished observations).…”