D. C. XXXX ORIGINAL XXX UK C. V Journal The Authors © 2007 compilation © 2007 0960-7722 & ARTICLES Cell HessPublishing Ltd Blackwell Publishing Ltd, Cell Proliferation, 41 (Suppl. 1), xx–xx. CPRProliferation . Borlongan Oxford, Blackwell
Stem cells and neurological diseases
D. C. Hess* and C. V. Borlongan* ,†
*Department of Neurology, MedicalCollege of Georgia, and †Medical Research Service, VA Medical Center, Augusta, GA 30912, USA Received 14 February 2007; revision accepted 11 April 2007
Abstract. Cells of the central nervous system were once thought to be incapable of regeneration. This dogma has been challenged in the last decade with studies showing new, migrating stem cells in the brain in many rodent injury models and ﬁndingsof new neurones in the human hippocampus in adults. Moreover, there are reports of bone marrow-derived cells developing neuronal and vascular phenotypes and aiding in repair of injured brain. These ﬁndings have fuelled excitement and interest in regenerative medicine for neurological diseases, arguably the most difﬁcult diseases to treat. There are numerous proposed regenerative approaches toneurological diseases. These include cell therapy approaches in which cells are delivered intracerebrally or are infused by an intravenous or intra-arterial route; stem cell mobilization approaches in which endogenous stem and progenitor cells are mobilized by cytokines such as granulocyte colony stimulatory factor (GCSF) or chemokines such as SDF-1; trophic and growth factor support, such asdelivering brain-derived neurotrophic factor (BDNF) or glialderived neurotrophic factor (GDNF) into the brain to support injured neurones; these approaches may be used together to maximize recovery. While initially, it was thought that cell therapy might work by a ‘cell replacement’ mechanism, a large body of evidence is emerging that cell therapy works by providing trophic or ‘chaperone’ support to theinjured tissue and brain. Angiogenesis and neurogenesis are coupled in the brain. Increasing angiogenesis with adult stem cell approaches in rodent models of stroke leads to preservation of neurones and improved functional outcome. A number of stem and progenitor cell types has been proposed as therapy for neurological disease ranging from neural stem cells to bone marrow derived stem cells toembryonic stem cells. Any cell therapy approach to neurological disease will have to be scalable and easily commercialized if it will have the necessary impact on public health. Currently, bone marrow-derived cell populations such as the marrow stromal cell, multipotential progenitor cells, umbilical cord stem cells and neural stem cells meet these criteria the best. Of great clinical signiﬁcance,initial evidence suggests these cell types may be delivered by an allogeneic approach, so strict tissue matching may not be necessary. The most immediate impact on patients will be achieved by making use of the trophic support capability of cell therapy and not by a cell replacement mechanism.
Correspondence: David C. Hess, Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA.Tel.: 706 721 1691; Fax: 706 721 7619; E-mail: firstname.lastname@example.org Both authors have received grant support from Athersys, Inc, Cleveland, Ohio. 94
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Stem cells and neurological diseases
Until recently, cells of the brain and central nervous system were thought to be incapable of regeneration. In1928, Ramon y Cajal wrote, ‘In adult centres, the nerve paths are something ﬁxed, ended, immobile. Everything may die, nothing may be regenerated.’ However, even Ramon y Cajal left it open to future generations to change ‘this harsh decree’. Vertebrates such as the urodele amphibians show a remarkable plasticity of the central nervous system, able to regenerate tails and limbs (Brockes 1997; Brockes...