Transplants of Schwann cell cultures promote axonal regeneration in the adult mammalian brain.

Abstract

Transplantation of embryonic brain tissue or mature peripheral nerves into the adult mammalian central nervous system promotes axonal regrowth from axotomized central nervous system neurons; however, the Since peripheral nerves possess a relatively well-defined cellular environment composed primarily of axons, Sc, fibroblasts, and extracellular matrix (ECM), this tissue provides an excellent source of material for cell culture preparations that can be used for the isolation and identification of cellular or extracellular factors responsible for promoting axonal growth. Cell culture preparations have been employed to show that neurite growth in vitro is enhanced either by culturing neurons in an environment containing heart-or Sc-conditioned-medium factors bound to a culture substratum (11, 12) or by plating CNS neurons onto monolayers of Sc or astrocytes (13,14). Experiments with nonmammalian vertebrate tissue (15) and predegenerated, frozen-thawed mammalian sciatic nerve (16) indicate that acellular preparations of peripheral nerve ECM also may provide a growth substrate for regenerating peripheral axons in vivo. Moreover, one specific ECM component, laminin, has been implicated as a neurite-promoting molecule for both .To successfully promote axonal regeneration in the adult mammalian CNS, it is important to extend the results obtained from in vitro preparations to a direct in vivo paradigm. Thus, the present study was undertaken to devise a methodology that would combine the use of in vitro PNS cell preparations, which can provide selected cellular fractions, with the technique of intracephalic tissue transplantation. By utilizing these combined procedures, it has been possible to demonstrate that transplants of mature cultures of Sc associated with ECM have a profound positive effect on axonal regeneration in the lesioned brain of adult mammals. Moreover, this study establishes a methodology whereby a variety of cellular components can be transplanted in close proximity to lesioned CNS axons in order to evaluate the influence of a specific cellular environment on in vivo axonal regeneration from mature CNS neurons.t It has long been recognized that functional axonal regeneration can occur in the adult mammalian peripheral nervous system (PNS) after peripheral nerve damage (1, 2). In contrast, little spontaneous axonal regeneration occurs folAbbreviations: AcChoEase, acetylcholinesteraae; CNS, central nervous system; ECM, extracellular matrix; PNS, peripheral nervous system; Sc, Schwann cell(s).

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

“…Furthermore, the elimination of viable Schwann cells from peripheral nerve grafts abolishes the promotion of CNS regeneration [39][40][41]. Transplantation of Schwann cells into sites of CNS injury, including the lesioned spinal cord, mimics the effects of peripheral nerve grafts and supports axonal regeneration [42,43]. In addition to potentially myelinating regenerated axons, Schwann cells express cell adhesion molecules, produce components of the extracellular matrix, and secrete multiple neurotrophic factors [44][45][46][47][48][49][50][51][52][53].…”

Three-dimensional traction forces of Schwann cells on compliant substrates

“…In injuries, even at the scale of millimetres, endogenous SCs respond and are capable of guiding nerve fibres towards the distal stump (figure 1c). Moreover, although naturally not found in the central nervous system, transplantation of exogenous SCs into the brain [7] or the spinal cord [8,9] has promoted axonal regeneration. The means by which SCs accomplish successful migration and morphological organization across these scenarios remain unknown.…”

Long-Distance Axonal Regeneration in the Transected Adult Rat Spinal Cord Is Promoted by Olfactory Ensheathing Glia Transplants

“…Several groups have used purified SC transplants to stimulate axonal elongation in different injured CNS regions (Kromer and Cornbrooks, 1985;Guénard et al, 1993;Montgomery and Robson, 1993;Harvey et al, 1994;Xu et al, 1995aXu et al, , 1997. In transected spinal cords, SC-filled guidance channels may be grafted to bridge the gap created between the cord stumps (Xu et al, 1997).…”