Alginate encapsulated BDNF-producing fibroblast grafts permit recovery of function after spinal cord injury in the absence of immune suppression.
Encapsulation of cells has the potential to provide a protective barrier against host immune cell interactions after grafting. Previously we have shown that alginate encapsulated BDNF-producing fibroblasts (Fb/BDNF) survived for one month in culture, made bioactive neurotrophins, survived transplantation into the injured spinal cord in the absence of immune suppression, and provided a permissive environment for host axon growth. We extend these studies by examining the effects of grafting encapsulated Fb/BDNF into a subtotal cervical hemisection on recovery of forelimb and hindlimb function and axonal growth in the absence of immune suppression. Grafting of encapsulated Fb/BDNF resulted in partial recovery of forelimb usage in a test of vertical exploration and of hindlimb function while crossing a horizontal rope. Recovery was significantly greater compared to animals that received unencapsulated Fb/BDNF without immune suppression, but similar to that of immune suppressed animals receiving unencapsulated Fb/BDNF. Immunocytochemical examination revealed neurofilament (RT-97), 5-HT, CGRP and GAP-43 containing axons surrounding encapsulated Fb/BDNF within the injury site, indicating axonal growth. BDA labeling however showed no evidence of regeneration of rubrospinal axons in recipients of encapsulated Fb/BDNF, presumably because the amounts of BDNF available from the encapsulated grafts are substantially less than those provided by the much larger numbers of Fb/BDNF grafted in a gelfoam matrix in the presence of immune suppression. These results suggest that plasticity elicited by the BDNF released from the encapsulated cells contributed to reorganization that led to behavioral recovery in these animals and that the behavioral recovery could proceed in the absence of rubrospinal tract regeneration. Alginate encapsulation is therefore a feasible strategy for delivery of therapeutic products produced by non-autologous engineered fibroblasts and provides an environment suitable for recovery of lost function in the injured spinal cord.
Tobias
Christopher A
CA
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
Han
Steve S W
SS
Shumsky
Jed S
JS
Kim
Duckhyun
D
Tumolo
Maureen
M
Dhoot
Nikhil O
NO
Wheatley
Margaret A
MA
Fischer
Itzhak
I
Tessler
Alan
A
Murray
Marion
M
D000464:Alginates; D000818:Animals; D001369:Axons / Q000502:physiology; D001672:Biocompatible Materials; D002214:Capsules; D018929:Cell Culture Techniques; D017690:Cell Transplantation / Q000379:methods*; D002574:Cervical Vertebrae; D005260:Female; D005347:Fibroblasts / Q000637:transplantation*; D005552:Forelimb / Q000502:physiology; D020723:Glucuronic Acid; D006084:Graft Rejection / Q000517:prevention & control*; D006603:Hexuronic Acids; D006614:Hindlimb / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors
D000464:Alginates; D001672:Biocompatible Materials; D002214:Capsules; D006603:Hexuronic Acids; D020723:Glucuronic Acid