Effects of Schwann cell transplantation in a contusion model of rat spinal cord injury

Cultured Schwann cells were transplanted at various delays into a spinal cord contusion injury performed at low thoracic level in adult female rats. The Schwann cells were purified from the dorsal root ganglia of adult syngeneic animals. The transplants were well tolerated, and the transplanted Schwann cells invaded the injured spinal cord. As quantified using video image analysis, the survival and growth of the transplanted cells were poor when the grafting procedure was performed 3–4 days after injury and very good when performed immediately or 10 days after injury, in which cases post-traumatic micro- and macrocavitation were strongly reduced. In animals grafted immediately after injury but not in animals grafted after 10 days, post-traumatic astrogliosis was much reduced. The Schwann cells transplanted area was invaded by numerous regenerating axons, the vast majority of which were, based on the neurotransmitter (CGRP and SP) profile, originating from dorsal root ganglion. No regeneration of the cortico-spinal tract as assessed after anterograde tracing or of descending aminergic fibers could be demonstrated. © 1996 Wiley-Liss, Inc.     

Observation of cultured peripheral non-neuronal cells implanted into the transected spinal cord

Summary We have previously reported that cultured peripheral non-neuronal cells could be used as an adjunct to spinal cord reconstruction with the delayed nerve graft technique. The cultured cells appeared to enhance axonal regeneration and with their use the time it took for axons from the spinal cord stumps to reach the nerve graft was reduced. To gain insight into the possible mechanisms through which peripheral nonneuronal cells can foster CNS regeneration, we have now investigated the behaviour of the peripheral nonneuronal cells after implantation into the spinal cord. Autologous mixed non-neuronal cell cultures were prepared from cat sciatic nerve biopsies and labeled in culture with tritiated thymidine. The labeled cells were implanted so as to completely fill the gap in the spinal cord produced by a narrow slit transection. Light-and electron-microscopic autoradiography was used to identify the cells 3 and 7 days after implantation and to determine their proximity to, and possible interaction with, axons in the spinal cord stumps. The implanted peripheral cells were frequently found near spinal cord axons and axon terminals. Some of the labeled cells ensheathed axons in which case they displayed morphological characteristics of Schwann cells. Other labeled cells had characteristics of fibroblasts and were surrounded by an extracellular matrix rich in collagen fibrils. Many of the labeled cells contained phagocytosed myelin debris. These observations are consistent with the implanted cells acting to enhance regeneration in the spinal cord either by direct interaction with axons (ensheathment) or indirectly via the production of soluble neuronotrophic factors or a favorable extracellular matrix. The ability of the implanted cells to rapidly move into the spinal cord stumps and attain positions close to spinal cord axons would be an important factor for any of these mechanisms.Supported by grants from the Veterans Administration and the National Institutes of Health (NS-14413)     

Cell transplantation for the treatment of spinal cord injury–bone marrow stromal cells and choroid plexus epithelial cells

Transplantation of bone marrow stromal cells(BMSCs) enhanced the outgrowth of regenerating axons and promoted locomotor improvements of rats with spinal cord injury(SCI).BMSCs did not survive long-term,disappearing from the spinal cord within 2–3 weeks after transplantation.Astrocyte-devoid areas,in which no astrocytes or oligodendrocytes were found,formed at the epicenter of the lesion.It was remarkable that numerous regenerating axons extended through such astrocyte-devoid areas.Regenerating axons were associated with Schwann cells embedded in extracellular matrices.Transplantation of choroid plexus epithelial cells(CPECs) also enhanced axonal regeneration and locomotor improvements in rats with SCI.Although CPECs disappeared from the spinal cord shortly after transplantation,an extensive outgrowth of regenerating axons occurred through astrocyte-devoid areas,as in the case of BMSC transplantation.These findings suggest that BMSCs and CPECs secret neurotrophic factors that promote tissue repair of the spinal cord,including axonal regeneration and reduced cavity formation.This means that transplantation of BMSCs and CPECs promotes "intrinsic" ability of the spinal cord to regenerate.The treatment to stimulate the intrinsic regeneration ability of the spinal cord is the safest method of clinical application for SCI.It should be emphasized that the generally anticipated long-term survival,proliferation and differentiation of transplanted cells are not necessarily desirable from the clinical point of view of safety.     

Treatment of spinal cord injury with co-grafts of genetically modified schwann cells and fetal spinal cord cell suspension in the rat

Fetal spinal cord cells, Schwann cells and neurotrophins all have the capacity to promote repair of injured spinal cord in animal models. To explore the possibility of using these approaches to treat clinical patients, we have examined whether a combination of these protocols produces functional and anatomical improvement. The spinal cords of adult rats (n=16) were injured with a modified New York University (NYU) device (10 gram.5cm). One week after injury, the injured cords were injected with Dulbecco-modified Eagles Medium (DMEM, control group), or fetal spinal cord cell suspension (FSCS) plus nerve growth factor (NGF) gene-modified Schwann cells (SC) and brain-derived neurotrophic factor (BDNF) gene-modified SC (treatment group). The rats were subjected to BBB (Basso, Beattie, Bresnahan, Exp. Neurol. 139:244, 1996) behavioral tests. Anterograde tracing of corticospinal tract was performed before sacrifice 3 months after the treatment. The results showed that the combination treatment elicited a robust growth of corticospinal axons within and beyond the injury site. A dramatic functional recovery in the treatment group was observed compared with the control group. We conclude that the combination of FSCS with genetically modified Schwann cells over-expressing NGF and BDNF was an effective protocol for the treatment of severe spinal cord injury.     

大鼠脊髓损伤后PLGA支架细胞髓内移植的组织学观察

目的 观察神经干细胞(NSC)、许旺细胞(SCs)和组织工程材料乙交酯-丙交酯共聚物(PLGA)大鼠髓内共移植后的病理形态学改变.方法 36只Wistar大鼠,随机分为PLGA移植组、NSC/PLGA组和NSC+SCs/PLGA组.体外培养、鉴定胚胎脊髓源NSC和SCs,制备和构建PLGA支架细胞复合体并移植到大鼠脊髓Tq半横断损伤部位,应用HE染色、电镜和免疫组织化学染色方法在形态结构上观察材料的组织相容性、轴突髓鞘再生及NSC在脊髓内的存活、迁移和分化情况.结果 HE染色观察损伤12周时移植材料内可见细胞生长及新生的毛细血管;扫描电镜观察随着时间的延长,PLGA逐渐降解;材料正中横断面透射电镜观察可见新牛的无髓及有髓神经纤维;脊髓标本免疫组织化学染色可见移植的NSC可以在宿主脊髓内存活、迁移并分化成类神经元样细胞和少枝胶质细胞,未分化成星形胶质细胞.结论 NSC、SCs和PLGA共移植可以在形态学上促进大鼠脊髓半横断损伤的修复.     

A combination of insulin-like growth factor-I and platelet-derived growth factor enhances myelination but diminishes axonal regeneration into Schwann cell grafts in the adult rat spinal cord

Insulin-like growth factor-I (IGF-I) promotes axonal regeneration in the peripheral nervous system and this effect is enhanced by platelet-derived growth factor (PDGF). We decided, therefore, to study the effects of these factors on axonal regeneration in the adult rat spinal cord. Semipermeable polymer tubes, closed at the distal end, containing Matrigel mixed with cultured rat Schwann cells and IGF-I/PDGF, were placed at the proximal stump of the spinal cord after removal of the thoracic T9-11 segments. Control animals received implants of only Matrigel and Schwann cells or only Matrigel and IGF-I/PDGF. Four weeks after implantation, electron microscopic analysis showed that the addition of IGF-I/PDGF resulted in an increase in the myelinated:unmyelinated fiber ratio from 1:7 to 1:3 at 3 mm in the Schwann cell graft, and that myelin sheath thickness was increased 2-fold. The reduced number of unmyelinated axons was striking in electron micrographs. These results suggested that IGF-I/PDGF enhanced myelin formation of regenerated axons in Schwann cell implants, but there was a 36% decrease in the total number of myelinated axons at the 3 mm level of the graft. This finding and the altered myelinated:unmyelinated fiber ratio revealed that the overall fiber regeneration into Schwann cell implants was diminished up to 63% by IGF-I/PDGF. Histological evaluation revealed that there were more larger cavities in tissue at the proximal spinal cord-graft interface in animals receiving a Schwann cell implant with IGF-I/PDGF. Such cavitation might have contributed to the reduction in axonal ingrowth. In sum, the results indicate that whereas the combination of IGF-I and PDGF enhances myelination of regenerating spinal cord axons entering implants of Matrigel and Schwann cells after midthoracic transection, the overall regeneration of axons into such Schwann cell grafts is diminished. GLIA 19:247–258, 1997. © 1997 Wiley-Liss, Inc.     

Proteomic evaluation reveals that olfactory ensheathing cells but not Schwann cells express calponin

Human clinical trials have begun worldwide that use olfactory ensheathing cells (OECs) to ameliorate the functional deficits following spinal cord injury. These trials have been initiated largely because numerous studies have reported that OECs transform into Schwann Cell (SC)-like cells that myelinate axons and support new growth in adult rats with spinal injury. This phenomenon is remarkable because OECs do not myelinate olfactory axons in their native environment. Furthermore, these myelinating OECs are morphologically identical to SCs, which can invade the spinal cord after injury. One factor that has contributed to a possible confusion in the identification of these cells is the lack of phenotypic markers to distinguish unequivocally between OECs and SCs. Such markers are required to first assess the degree of SC contamination in OEC cultures before intraspinal implantation, and then to accurately identify grafted OECs and invading SCs in the injured spinal cord. Using two-dimensional gel electrophoresis, we have identified calponin, an actin binding protein, as the first definitive phenotypic marker that distinguishes between OECs and SCs in vitro and in vivo. We have also provided ultrastructural evidence that calponin-immunopositive OECs do not transform into myelinating SC-like cells after intraspinal implantation. Rather, the grafted OECs retain their morphological and neurochemical features. These data yield new insight into the phenotypic characteristics of OECs, which together with invading SCs can enhance regeneration of the injured spinal cord.     

Role of endogenous Schwann cells in tissue repair after spinal cord injury

Schwann cells are glial cells of peripheral nervous system, responsible for axonal myelination and ensheathing, as well as tissue repair following a peripheral nervous system injury. They are one of several cell types that are widely studied and most commonly used for cell transplantation to treat spinal cord injury, due to their intrinsic characteristics including the ability to secrete a variety of neurotrophic factors. This mini review summarizes the recent findings of endogenous Schwann cells after spinal cord injury and discusses their role in tissue repair and axonal regeneration. After spinal cord injury, numerous endogenous Schwann cells migrate into the lesion site from the nerve roots, involving in the construction of newly formed repaired tissue and axonal myelination. These invading Schwann cells also can move a long distance away from the injury site both rostrally and caudally. In addition, Schwann cells can be induced to migrate by minimal insults (such as scar ablation) within the spinal cord and integrate with astrocytes under certain circumstances. More importantly, the host Schwann cells can be induced to migrate into spinal cord by transplantation of different cell types, such as exogenous Schwann cells, olfactory ensheathing cells, and bone marrow-derived stromal stem cells. Migration of endogenous Schwann cells following spinal cord injury is a common natural phenomenon found both in animal and human, and the myelination by Schwann cells has been examined effective in signal conduction electrophysiologically. Therefore, if the inherent properties of endogenous Schwann cells could be developed and utilized, it would offer a new avenue for the restoration of injured spinal cord.     

Cellular GDNF delivery promotes growth of motor and dorsal column sensory axons after partial and complete spinal cord transections and induces remyelination

Glial cell line-derived neurotrophic factor (GDNF) is the prototypical member of a growth factor family that signals via the cognate receptors ret and GDNF-receptor alpha-1. The latter receptors are expressed on a variety of neurons that project into the spinal cord, including supraspinal neurons, dorsal root ganglia, and local neurons. Although effects of GDNF on neuronal survival in the brain have previously been reported, GDNF effects on injured axons of the adult spinal cord have not been investigated. Using an ex vivo gene delivery approach that provides both trophic support and a cellular substrate for axonal growth, we implanted primary fibroblasts genetically modified to secrete GDNF into complete and partial mid-thoracic spinal cord transection sites. Compared to recipients of control grafts expressing a reporter gene, GDNF-expressing grafts promoted significant regeneration of several spinal systems, including dorsal column sensory, regionally projecting propriospinal, and local motor axons. Local GDNF expression also induced Schwann cell migration to the lesion site, leading to remyelination of regenerating axons. Thus, GDNF exerts tropic effects on adult spinal axons and Schwann cells that contribute to axon growth after injury.     

The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury

Oligodendrocyte progenitor cells (OPCs) are the most proliferative and dispersed population of progenitor cells in the adult central nervous system, which allows these cells to rapidly respond to damage. Oligodendrocytes and myelin are lost after traumatic spinal cord injury (SCI), compromising efficient conduction and, potentially, the long-term health of axons. In response, OPCs proliferate and then differentiate into new oligodendrocytes and Schwann cells to remyelinate axons. This culminates in highly efficient remyelination following experimental SCI in which nearly all intact demyelinated axons are remyelinated in rodent models. However, myelin regeneration comprises only one role of OPCs following SCI. OPCs contribute to scar formation after SCI and restrict the regeneration of injured axons. Moreover, OPCs alter their gene expression following demyelination, express cytokines and perpetuate the immune response. Here, we review the functional contribution of myelin regeneration and other recently uncovered roles of OPCs and their progeny to repair following SCI.     

Transplantation of olfactory ensheathing cells or Schwann cells restores rapid and secure conduction across the transected spinal cord

Olfactory ensheathing cells (OECs) or Schwann cells were transplanted into the transected dorsal columns of the rat spinal cord to induce axonal regeneration. Electrophysiological recordings were obtained in an isolated spinal cord preparation. Without transplantation of cells, no impulse conduction was observed across the transection site; but following cell transplantation, impulse conduction was observed for over a centimeter beyond the lesion. Cell labelling indicated that the regenerated axons were derived from the appropriate neuronal source, and that donor cells migrated into the denervated host tract. As reported in previous studies, the number of regenerated axons was limited. Conduction velocity measurements and morphology indicated that the regenerated axons were myelinated, but conducted faster and had larger axon areas than normal axons. These results indicate that the regenerated spinal cord axons induced by cell transplantation provide a quantitatively limited but rapidly conducting new pathway across the transection site.     

Tanycytes transplanted into the adult rat spinal cord support the regeneration of lesioned axons

During past years a number of therapeutic strategies have been developed in order to stimulate axonal regeneration after traumatic injuries of the spinal cord. Recently, encouraging data have been obtained by grafting specific glial cells such as Schwann cells or olfactory ensheathing glial cells, known to support the regeneration of peripheral or central axons, respectively. In a recent series of studies, we have shown that tanycytes, a particular glial cell type present in the mediobasal hypothalamus, were able to support the regeneration of a variety of axons innervating this region. The aim of the present study was to determine whether tanycytes could also support the regeneration of lesioned spinal axons. Cultured hypothalamic tanycytes and cortical astrocytes were prelabeled with Fast blue (FB) and grafted into the thoracic spinal cord of adult rats. Three weeks after the transplantation, the animals were fixed and spinal cord sections treated for multiple fluorescence detection of the FB-labeled transplanted cells on the one hand and of various glial and neuronal markers on the other hand. We show here that in all the spinal cords examined, transplanted tanycytes or astrocytes formed large spherical clusters of about 0.5 mm in diameter, located in the mediolateral spinal cord layer. The immunodetection of glial markers showed that transplanted astrocytes exhibited intense immunostaining for both glial fibrillary acidic protein (GFAP) and vimentin (VIM), whereas transplanted tanycytes were intensely immunostained for VIM, but GFAP negative. The immunodetection of axonal markers showed that contrasting with astrocyte transplants, tanycyte transplants were invaded by numerous axonal fibers. These data indicate that tanycyte transplants may represent a useful therapeutic tool for the reparation of the lesioned spinal axons.     

Nerve growth factor-hypersecreting Schwann cell grafts augment and guide spinal cord axonal growth and remyelinate central nervous system axons in a phenotypically appropriate manner that correlates with expression of L1.

Schwann cells contribute to efficient axonal regeneration after peripheral nerve injury and, when grafted to the central nervous system (CNS), also support a modest degree of central axonal regeneration. This study examined (1) whether Schwann cells grafted to the CNS exhibit normal patterns of differentiation and association with spinal axons and what signals putatively modulate these interactions, and (2) whether Schwann cells overexpressing neurotrophic factors enhance axonal regeneration. Thus, primary Schwann cells were transduced to hypersecrete human nerve growth factor (NGF) and were grafted to spinal cord injury sites in adult rats. Comparisons were made to nontransfected Schwann cells. From 3 days to 6 months later, grafted Schwann cells exhibited a phenotypic and temporal course of differentiation that matched patterns normally observed after peripheral nerve injury. Schwann cells spontaneously aligned into regular spatial arrays within the cord, appropriately remyelinated coerulospinal axons that regenerated into grafts, and appropriately ensheathed but did not myelinate sensory axons extending into grafts. Coordinate expression of the cell adhesion molecule L1 on Schwann cells and axons correlated with establishment of appropriate patterns of axon-Schwann cell ensheathment. Transduction of Schwann cells to overexpress NGF robustly increased axonal growth but did not otherwise alter the nature of interactions with growing axons. These findings suggest that signals expressed on Schwann cells that modulate peripheral axonal regeneration and myelination are also recognized in the CNS and that the modification of Schwann cells to overexpress growth factors significantly augments their capacity to support extensive axonal growth in models of CNS injury.     

Olfactory ensheathing glia: their contribution to primary olfactory nervous system regeneration and their regenerative potential following transplantation into the injured spinal cord

Olfactory ensheathing glia (OEG) are a specialized type of glia that guide primary olfactory axons from the neuroepithelium in the nasal cavity to the brain. The primary olfactory system is able to regenerate after a lesion and OEG contribute to this process by providing a growth-supportive environment for newly formed axons. In the spinal cord, axons are not able to restore connections after an injury. The effects of OEG transplants on the regeneration of the injured spinal cord have been studied for over a decade. To date, of all the studies using only OEG as a transplant, 41 showed positive effects, while 13 studies showed limited or no effects. There are several contradictory reports on the migratory and axon growth-supporting properties of transplanted OEG. Hence, the regenerative potential of OEG has become the subject of intense discussion. In this review, we first provide an overview of the molecular and cellular characteristics of OEG in their natural environment, the primary olfactory nervous system. Second, their potential to stimulate regeneration in the injured spinal cord is discussed. OEG influence scar formation by their ability to interact with astrocytes, they are able to remyelinate axons and promote angiogenesis. The ability of OEG to interact with scar tissue cells is an important difference with Schwann cells and may be a unique characteristic of OEG. Because of these effects after transplantation and because of their role in primary olfactory system regeneration, the OEG can be considered as a source of neuroregeneration-promoting molecules. To identify these molecules, more insight into the molecular biology of OEG is required. We believe that genome-wide gene expression studies of OEG in their native environment, in culture and after transplantation will ultimately reveal unique combinations of molecules involved in the regeneration-promoting potential of OEG.     

Mats made from fibronectin support oriented growth of axons in the damaged spinal cord of the adult rat

A variety of biological as well as synthetic implants have been used to attempt to promote regeneration into the damaged spinal cord. We have implanted mats made from fibronectin (FN) into the damaged spinal cord to determine their effectiveness as a substrate for regeneration of axons. These mats contain oriented pores and can take up and release growth factors. Lesion cavities 1 mm in width and depth and 2 mm in length were created on one side of the spinal cord of adult rats. FN mats containing neurotrophins or saline were placed into the lesion. Mats were well integrated into surrounding tissue and showed robust well-oriented growth of calcitonin gene-related peptide, substance P, GABAergic, cholinergic, glutamatergic, and noradrenergic axons into FN mats. Transganglionic tracing using cholera toxin B indicated large-diameter primary afferents had grown into FN implants. Schwann cells had also infiltrated FN mats. Electron microscopy confirmed the presence of axons within implants sites, with most axons either ensheathed or myelinated by Schwann cells. Mats incubated in brain-derived neurotrophic factor and neurotrophin-3 showed significantly more neurofilament-positive and glutamatergic fibers compared to saline- and nerve growth factor-incubated mats, while mats incubated with nerve growth factor showed more calcitonin gene-related peptide-positive axons. In contrast, neurotrophin treatment had no effect on PGP 9.5-positive axons. In addition, in some animals with neurotrophin-3-incubated mats, cholera toxin B-labelled fibers had grown from the mat into adjoining intact areas of spinal cord. The results indicate that FN mats provide a substrate that is permissive for robust oriented axonal growth in the damaged spinal cord, and that this growth is supported by Schwann cells.     

Early profiles of axonal growth and astroglial response after spinal cord hemisection and implantation of Schwann cell-seeded guidance channels in adult rats

We previously demonstrated that transplantation of Schwann cell-seeded channels promoted the regrowth of injured axons in the adult spinal cord. It is not clear, however, whether injured axons recapitulate the developmental scenarios to accomplish regeneration. In the present study, we investigated the early events associated with axonal regrowth after spinal cord hemisection at the eighth thoracic level and implantation of a Schwann cell-seeded minichannel in adult rats. Animals were sacrificed at postoperative days (PO) 2, 4, 7, and 14. Anterograde tracing with fluoro-ruby showed that regenerating axons grew into the graft prior to PO2 and reached the distal end of the channel at PO7. These axons expressed both embryonic neural cell adhesion molecule (E-NCAM) and growth associated protein-43 (GAP-43). Although the expression of E-NCAM decreased by PO7, that of GAP-43 remained high throughout the first 2 weeks after implantation. A close relation of vimentin-positive astroglia to the growing axons in the host tissue suggested a contact-mediated role of these cells in axon guidance. Aggregation of glial fibrillary acidic protein (GFAP)-positive astrocytes together with the increased expression of chondroitin sulfate proteoglycans (CSPGs) starting at PO7 appeared to inhibit axonal growth at the host-graft interface. Thus, adult regenerating axons and astroglia do express developmentally related molecules that may facilitate axonal growth into a permissive graft at the early phase of injury and regeneration. These results suggest that molecules and astroglia essential to development are both important in influencing axonal regrowth in the adult spinal cord.     

Demyelination and Schwann cell responses adjacent to injury epicenter cavities following chronic human spinal cord injury

The natural history of post-traumatic demyelination and myelin repair in the human spinal cord is largely unknown and has remained a matter of speculation. A wealth of experimental studies indicate that mild to moderate contusive injuries to the mammalian spinal cord evolve into a cavity with a preserved rim of white matter in which a population of segmentally demyelinated axons persists. It is believed that such injured axons have abnormal conduction properties. Theoretically, such axons might show improved function if myelin repair occurred. Schwann cells can remyelinate axons affected by multiple sclerosis, but little evidence exists that such repair can occur spontaneously following traumatic human SCI. Therefore, it is important to determine if chronic demyelination is present following human spinal cord injury. There are no previous reports that have conclusively demonstrated demyelination in the human spinal cord following traumatic spinal cord injury using immunohistochemical techniques. Immunohistochemical methods were used to study the distribution of peripheral and central myelin proteins as well as axonal neurofilament at the injury epicenter in 13 postmortem chronically injured human spinal cords 1-22 years following injury. Of these seven could be assessed by our methods. We found that some axonal demyelination can be detected even a decade following human SCI and indirect evidence that invading Schwann cells contributed to restoration of myelin sheaths around some spinal axons.     

Regeneration into the Spinal Cord of Transected Dorsal Root Axons Is Promoted by Ensheathing Glia Transplants

The permissivity of adult olfactory bulb to the ingrowth of olfactory axons could be due to the unique properties of ensheathing glia. To test whether these glial cells could be used to promote axonal regeneration in a spontaneously nonregenerating system, we transplanted suspensions of pure ensheathing cells into a rhizotomized spinal cord segment. Ensheathing cells were purified away from other cell types by immunoaffinity, using anti-p75 nerve growth factor receptor. After laminectomy at the lower thoracic level, the spinal cord was exposed and one dorsal root (T10) was completely transected at the cord entry point. The root stump was microsurgically anastomosed to the cord and a suspension of ensheathing cells was transplanted in the spinal cord at the dorsal root entry zone. Three weeks after transplantation, numerous regenerating dorsal root axons were observed reentering the spinal cord. Ingrowth of dorsal root axons was observed using Dil and antibodies against calcitonin gene-related peptide and growth-associated protein. Primary sensory afferents invaded laminae 1, 2, and 3, grew through laminae 4 and 5, and reached the dorsal grey commissure and lamina 4 of the contralateral side. We did not observe regenerating axons within the ipsilateral ventral horn and dorsal column. Transplanted ensheathing cells reached the same laminae as axons. Neither ensheathing cells nor regenerating axons invaded those laminae they did not inervate under normal circumstances. In conclusion, the regeneration of injured dorsal root axons into the adult spinal cord was possible after ensheathing glia transplantation. The use of ensheathing cells as stimulators of axonal growth might be generalized to other central nervous system injuries.     

The growth of motoneurones and their neurites in relation to Schwann cells harvested from sciatic nerve

A study has been made of the effects of Schwann cells isolated from neonatal sciatic nerve on motoneurones in culture. Motoneurones were identified in dissociated spinal cord cultures from 6-day avian embryos by prior retrograde labelling with rhodamine-latex microspheres. Schwann cells trebled the expression of long neurites in these motoneurones over that in control media as well as maintaining them viable for 24 h. A transformed Schwann cell line, RN22, produced similar results. These effects were mediated by a soluble factor(s) released from the Schwann cells which was distinct from nerve growth factor. Schwann cells exerted this initiation of neurites on homogeneous cultures of motoneurones, indicating that other spinal cord cells are not necessary to mediate this effect. The observations are discussed in terms of the hypothesis that Schwann cells guide motor axons during regeneration and formation of limb and muscle nerves.